{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T18:59:27Z","timestamp":1793386767502,"version":"4.5.0"},"reference-count":206,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T00:00:00Z","timestamp":1678406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>\u03b2-lactam antibiotics are one of the most widely used and diverse classes of antimicrobial agents for treating both Gram-negative and Gram-positive bacterial infections. The \u03b2-lactam antibiotics, which include penicillins, cephalosporins, monobactams and carbapenems, exert their antibacterial activity by inhibiting the bacterial cell wall synthesis and have a global positive impact in treating serious bacterial infections. Today, \u03b2-lactam antibiotics are the most frequently prescribed antimicrobial across the globe. However, due to the widespread use and misapplication of \u03b2-lactam antibiotics in fields such as human medicine and animal agriculture, resistance to this superlative drug class has emerged in the majority of clinically important bacterial pathogens. This heightened antibiotic resistance prompted researchers to explore novel strategies to restore the activity of \u03b2-lactam antibiotics, which led to the discovery of \u03b2-lactamase inhibitors (BLIs) and other \u03b2-lactam potentiators. Although there are several successful \u03b2-lactam-\u03b2-lactamase inhibitor combinations in use, the emergence of novel resistance mechanisms and variants of \u03b2-lactamases have put the quest of new \u03b2-lactam potentiators beyond precedence. This review summarizes the success stories of \u03b2-lactamase inhibitors in use, prospective \u03b2-lactam potentiators in various phases of clinical trials and the different strategies used to identify novel \u03b2-lactam potentiators. Furthermore, this review discusses the various challenges in taking these \u03b2-lactam potentiators from bench to bedside and expounds other mechanisms that could be investigated to reduce the global antimicrobial resistance (AMR) burden.<\/jats:p>","DOI":"10.3389\/fmicb.2022.1092556","type":"journal-article","created":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T23:58:57Z","timestamp":1678406337000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":92,"title":["\u03b2-Lactam potentiators to re-sensitize resistant pathogens: Discovery, development, clinical use and the way forward"],"prefix":"10.3389","volume":"13","author":[{"given":"Lekshmi","family":"Narendrakumar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Medha","family":"Chakraborty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shashi","family":"Kumari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepjyoti","family":"Paul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhabatosh","family":"Das","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,10]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"13500","DOI":"10.1038\/srep13500","article-title":"An efficient system for intracellular delivery of beta-lactam antibiotics to overcome bacterial resistance","volume":"5","author":"Abed","year":"2015","journal-title":"Sci. Rep."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1186\/s13756-020-00838-y","article-title":"\u03b2-Lactamase-mediated resistance in MDR-Pseudomonas aeruginosa from Qatar","volume":"9","author":"Ahmed","year":"2020","journal-title":"Antimicrob. Resist. Infect. Control"},{"key":"ref3","doi-asserted-by":"crossref","DOI":"10.1007\/978-981-16-9097-6_3","article-title":"Beta-lactamases and their classification: an overview","volume-title":"Beta-lactam resistance in gram-negative bacteria","author":"Akhtar","year":"2022"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1111\/j.1469-0691.2007.01847.x","article-title":"Sulbactam-containing beta-lactamase inhibitor combinations","volume":"14","author":"Akova","year":"2008","journal-title":"Clin. Microbiol. Infect."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1080\/17460441.2022.2113774","article-title":"Metabolomics in antimicrobial drug discovery","volume":"17","author":"Aminov","year":"2022","journal-title":"Expert Opin. Drug Discov."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/j.mimet.2012.09.033","article-title":"In situ potentiometric method to evaluate bacterial outer membrane-permeabilizing ability of drugs: example using antiprotozoal diamidines","volume":"91","author":"Ando","year":"2012","journal-title":"J. Microbiol. Methods"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1612","DOI":"10.1128\/AAC.39.7.1612","article-title":"A novel integron-like element carrying the metallo-\u03b2-lactamase gene blaIMP","volume":"39","author":"Arakawa","year":"1995","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1097\/SMJ.0b013e3181fd7d5a","article-title":"Emergence of Klebsiella pneumoniae carbapenemase-producing bacteria","volume":"104","author":"Arnold","year":"2011","journal-title":"South. Med. J."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"30699","DOI":"10.1073\/pnas.1922187117","article-title":"Transcriptome-based design of antisense inhibitors potentiates carbapenem efficacy in CRE Escherichia coli","volume":"117","author":"Aunins","year":"2020","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1177\/106002808802200702","article-title":"Sulbactam\/ampicillin, a new Beta-lactamase inhibitor\/Beta-lactam antibiotic combination","volume":"22","author":"Benson","year":"1988","journal-title":"Drug Intell. Clin. Pharm."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1697","DOI":"10.1038\/s41598-018-19752-w","article-title":"AmPEP: sequence-based prediction of antimicrobial peptides using distribution patterns of amino acid properties and random forest","volume":"8","author":"Bhadra","year":"2018","journal-title":"Sci. Rep."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"e00552-18","DOI":"10.1128\/aac.00552-18","article-title":"In vitro activity of LYS228, a novel Monobactam antibiotic, against multidrug-resistant Enterobacteriaceae","volume":"62","author":"Blais","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1016\/j.bmcl.2013.12.101","article-title":"Discovery of MK-7655, a \u03b2-lactamase inhibitor for combination with Primaxin\u00ae","volume":"24","author":"Blizzard","year":"2014","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1128\/aac.49.2.849-852.2005","article-title":"Selected Arylpiperazines are capable of reversing multidrug resistance in Escherichia coli overexpressing RND efflux pumps","volume":"49","author":"Bohnert","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1093\/jac\/dkh358","article-title":"In vitro activity of AVE1330A, an innovative broad-Spectrum non-lactam \u03b2-lactamase inhibitor","volume":"54","author":"Bonnefoy","year":"2004","journal-title":"J. Antimicrob. Chemother."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1016\/S0006-291X(03)00074-3","article-title":"Imipenem and expression of multidrug efflux pump in Enterobacter aerogenes","volume":"301","author":"Bornet","year":"2003","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"2483","DOI":"10.1093\/jac\/dkx179","article-title":"Emergence of ceftazidime\/avibactam non-susceptibility in an MDR Klebsiella pneumoniae isolate","volume":"72","author":"Both","year":"2017","journal-title":"J. Antimicrob. Chemother."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"96","DOI":"10.2165\/00003495-198631020-00002","article-title":"Aztreonam. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use","volume":"31","author":"Brogden","year":"1986","journal-title":"Drugs"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1042\/bj0500168","article-title":"Isolation of antibiotics from a species of Cephalosporium. Cephalosporins P1, P2, P3, P4 and P5","volume":"50","author":"Burton","year":"1951","journal-title":"Biochem. J."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1128\/CMR.1.1.109","article-title":"Beta-lactamase inhibitors from laboratory to clinic","volume":"1","author":"Bush","year":"1988","journal-title":"Clin. Microbiol. Rev."},{"key":"ref1004","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1016\/j.ijantimicag.2015.08.011","article-title":"A resurgence of \u03b2-lactamase inhibitor combinations effective against multidrug-resistant Gram-negative pathogens","volume":"46","author":"Bush","year":"2015","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"a025247","DOI":"10.1101\/cshperspect.a025247","article-title":"\u03b2-Lactams and \u03b2-lactamase inhibitors: an overview","volume":"6","author":"Bush","year":"2016","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1128\/AAC.01009-09","article-title":"Updated functional classification of beta-lactamases","volume":"54","author":"Bush","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1277","DOI":"10.1517\/13543776.2010.515588","article-title":"New \u03b2-lactam antibiotics and \u03b2-lactamase inhibitors","volume":"20","author":"Bush","year":"2010","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1159\/000516643","article-title":"CRISPR-Cas system: the powerful modulator of accessory genomes in prokaryotes","volume":"32","author":"Butiuc-Keul","year":"2022","journal-title":"Microb. Physiol."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"577","DOI":"10.2165\/00003495-198733060-00003","article-title":"Sulbactam\/ampicillin. A review of its antibacterial activity, pharmacokinetic properties, and therapeutic use","volume":"33","author":"Campoli-Richards","year":"1987","journal-title":"Drugs"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"1291","DOI":"10.1016\/j.molcel.2019.04.001","article-title":"Metabolomics-driven exploration of the chemical drug space to predict combination antimicrobial therapies","volume":"74","author":"Campos","year":"2019","journal-title":"Mol. Cell"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"53","DOI":"10.3389\/fchem.2019.00053","article-title":"Chemical proteomics-guided identification of a novel biological target of the bioactive Neolignan Magnolol","volume":"7","author":"Cassiano","year":"2019","journal-title":"Front. Chem."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1113\/jphysiol.1983.sp014769","article-title":"Reserpine has a direct action as a calcium antagonist on mammalian smooth muscle cells","volume":"340","author":"Casteels","year":"1983","journal-title":"J. Physiol."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/0165-6147(79)90004-x","article-title":"The early years of the penicillin discovery","volume":"1","author":"Chain","year":"1979","journal-title":"Trends Pharmacol. Sci."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jgeb.2018.01.006","article-title":"Omics based approach for biodiscovery of microbial natural products in antibiotic resistance era","volume":"16","author":"Chandra Mohana","year":"2018","journal-title":"J. Genet. Eng. Biotechnol."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1016\/j.bjid.2017.02.007","article-title":"Safety and efficacy of a novel drug elores (ceftriaxone+sulbactam+disodium edetate) in the management of multi-drug resistant bacterial infections in tertiary care centers: a post-marketing surveillance study","volume":"21","author":"Chaudhary","year":"2017","journal-title":"Braz. J. Infect. Dis."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"887251","DOI":"10.3389\/fmicb.2022.887251","article-title":"Antibiotic Potentiators against multidrug-resistant bacteria: discovery, development, and clinical relevance","volume":"13","author":"Chawla","year":"2022","journal-title":"Front. Microbiol."},{"key":"ref1003","doi-asserted-by":"publisher","first-page":"2732","DOI":"10.3389\/fmicb.2019.02732","article-title":"OXA-830, a Novel Chromosomally Encoded Extended-Spectrum Class D \u03b2-Lactamase in Aeromonas simiae","volume":"10","author":"Chen","year":"2019","journal-title":"Front Microbiol."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"1678","DOI":"10.1046\/j.1432-1327.2002.02815.x","article-title":"Increase of the deacylation rate of PBP2x from Streptococcus pneumoniae by single point mutations mimicking the class a beta-lactamases","volume":"269","author":"Chesnel","year":"2002","journal-title":"Eur. J. Biochem."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"9543","DOI":"10.1039\/c5cc02594j","article-title":"Ebselen as a potent covalent inhibitor of New Delhi metallo-\u03b2-lactamase (NDM-1)","volume":"51","author":"Chiou","year":"2015","journal-title":"Chem Comm."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"953","DOI":"10.3389\/fmicb.2019.00953","article-title":"Distinct roles of outer membrane Porins in antibiotic resistance and membrane integrity in Escherichia coli","volume":"10","author":"Choi","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"2804","DOI":"10.1093\/jac\/dkw209","article-title":"Heterogeneous oxacillin-resistant phenotypes and production of PBP2A by oxacillin-susceptible\/mec a-positive MRSA strains from Africa","volume":"71","author":"Chung","year":"2016","journal-title":"J. Antimicrob. Chemother."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1093\/jac\/45.1.9","article-title":"Chromosomal beta-lactamase is packaged into membrane vesicles and secreted from Pseudomonas aeruginosa","volume":"45","author":"Ciofu","year":"2000","journal-title":"J. Antimicrob. Chemother."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"16297","DOI":"10.1073\/pnas.1008608107","article-title":"Genome mining and genetic analysis of cypemycin biosynthesis reveal an unusual class of post-translationally modified peptides","volume":"107","author":"Claesen","year":"2010","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1177\/2472555217728489","article-title":"A rapid phenotypic whole-cell screening approach for the identification of small-molecule inhibitors that counter \u03b2-lactamase resistance in Pseudomonas aeruginosa","volume":"23","author":"Collia","year":"2018","journal-title":"SLAS Discov."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"1530","DOI":"10.1128\/aac.01132-06","article-title":"Genetics and expression of the Carbapenem-hydrolyzing Oxacillinase gene Bla OXA-23 in Acinetobacter baumannii","volume":"51","author":"Corvec","year":"2007","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1007\/s00253-021-11102-7","article-title":"Simultaneous elucidation of antibiotic mechanism of action and potency with high-throughput Fourier-transform infrared (FTIR) spectroscopy and machine learning","volume":"105","author":"Cunha","year":"2021","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1007\/s15010-020-01547-9","article-title":"Are antibacterial effects of non-antibiotic drugs random or purposeful because of a common evolutionary origin of bacterial and mammalian targets?","volume":"49","author":"Dalhoff","year":"2021","journal-title":"Infection"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1186\/s12879-020-05059-7","article-title":"Antibiotic prescribing among patients with severe infectious diseases in two private sector hospitals in Central India \u2013 a time series analysis over 10 years","volume":"20","author":"Damlin","year":"2020","journal-title":"BMC Infect. Dis."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"617","DOI":"10.3390\/ijms22020617","article-title":"The odd couple(s): an overview of Beta-lactam antibiotics bearing more than one Pharmacophoric group","volume":"22","author":"De Rosa","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"1402","DOI":"10.1016\/j.cell.2014.08.032","article-title":"A systematic analysis of biosynthetic gene clusters in the human microbiome reveals a common family of antibiotics","volume":"158","author":"Donia","year":"2014","journal-title":"Cells"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1093\/jac\/dkp029","article-title":"Molecular mechanisms disrupting porin expression in ertapenem-resistant Klebsiella and Enterobacter spp. clinical isolates from the UK","volume":"63","author":"Doumith","year":"2009","journal-title":"J. Antimicrob. Chemother."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"12511","DOI":"10.1021\/acs.jmedchem.0c00579","article-title":"Discovery of an orally available Diazabicyclooctane inhibitor (ETX 0282) of class A, C, and D serine \u03b2-lactamases","volume":"63","author":"Durand-R\u00e9ville","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"11663","DOI":"10.1073\/pnas.1205073109","article-title":"Avibactam is a covalent, reversible, non-\u03b2-lactam \u03b2-lactamase inhibitor","volume":"109","author":"Ehmann","year":"2012","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"e00074","DOI":"10.1128\/AAC.00074-18","article-title":"Discovery of a novel Metallo-\u03b2-lactamase inhibitor that potentiates Meropenem activity against Carbapenem-resistant Enterobacteriaceae","volume":"62","author":"Everett","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1016\/j.ijbiomac.2021.12.035","article-title":"A novel combination therapy for multidrug resistant pathogens using chitosan nanoparticles loaded with \u03b2-lactam antibiotics and \u03b2-lactamase inhibitors","volume":"195","author":"Fan","year":"2022","journal-title":"Int. J. Biol. Macromol."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1186\/s12929-019-0561-6","article-title":"Natural outer membrane permeabilizers boost antibiotic action against irradiated resistant bacteria","volume":"26","author":"Farrag","year":"2019","journal-title":"J. Biomedl. Sci."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"107","DOI":"10.21608\/jsrs.2015.18358","article-title":"Synergistic effect of certain natural permeabilizers with antimicrobial agents on outer membrane of some multidrug gram-negative pathogenic bacteria","volume":"32","author":"Farrag","year":"2015","journal-title":"J. Sci. Res. Sci."},{"key":"ref54","year":"2019"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"62","DOI":"10.3390\/antibiotics8020062","article-title":"A 2-year single-Centre audit on antibiotic resistance of Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae strains from an intensive care unit and other wards in a general public hospital in Greece","volume":"8","author":"Feretzakis","year":"2019","journal-title":"Antibiotics"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"1877","DOI":"10.1128\/AAC.05402-11","article-title":"Expression of OXA-type and SFO-1 \u03b2-lactamases induces changes in peptidoglycan composition and affects bacterial fitness","volume":"56","author":"Fern\u00e1ndez","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref57","doi-asserted-by":"publisher","first-page":"3198","DOI":"10.3389\/fmicb.2018.03198","article-title":"High prevalence of multidrug-resistant Klebsiella pneumoniae harboring several virulence and \u03b2-lactamase encoding genes in a Brazilian intensive care unit","volume":"9","author":"Ferreira","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref58","doi-asserted-by":"publisher","first-page":"8181","DOI":"10.1038\/s41598-018-26079-z","article-title":"Proteomic identification of Axc, a novel beta-lactamase with carbapenemase activity in a meropenem-resistant clinical isolate of Achromobacter xylosoxidans","volume":"8","author":"Fleurbaaij","year":"2018","journal-title":"Sci. Rep."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"57974","DOI":"10.7554\/elife.57974","article-title":"Breaking antimicrobial resistance by disrupting extra-cytoplasmic protein folding","volume":"11","author":"Furniss","year":"2022","journal-title":"eLife"},{"key":"ref60","doi-asserted-by":"publisher","first-page":"979","DOI":"10.3390\/antibiotics10080979","article-title":"Multidrug-resistant Klebsiella pneumoniae causing severe infections in the neuro-ICU","volume":"10","author":"Fursova","year":"2021","journal-title":"Antibiotics (Basel)."},{"key":"ref61","doi-asserted-by":"publisher","first-page":"5047","DOI":"10.1128\/AAC.00168-16","article-title":"Modeling Meropenem treatment, alone and in combination with Daptomycin, for KPC-producing Klebsiella pneumoniae strains with unusually low Carbapenem MICs","volume":"60","author":"Gagetti","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref62","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1093\/jac\/dkh545","article-title":"In vitro activity and killing effect of temporin a on nosocomial isolates of enterococcus faecalis and interactions with clinically used antibiotics","volume":"55","author":"Giacometti","year":"2005","journal-title":"J. Antimicrob. Chemother."},{"key":"ref63","doi-asserted-by":"publisher","first-page":"2211","DOI":"10.1128\/AAC.00035-12","article-title":"Escherichia coli from Italy producing OXA-48 carbapenemase encoded by a novel Tn1999 transposon derivative","volume":"56","author":"Giani","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref64","doi-asserted-by":"publisher","first-page":"e02101","DOI":"10.1128\/AAC.02101-17","article-title":"Successive emergence of ceftazidime-avibactam resistance through distinct genomic adaptations in-harboring Klebsiella pneumoniae sequence type 307 isolates","volume":"62","author":"Giddins","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref65","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1586\/14787210.5.3.365","article-title":"Piperacillin-tazobactam: a beta-lactam\/beta-lactamase inhibitor combination","volume":"5","author":"Gin","year":"2007","journal-title":"Expert Rev. Anti-Infect. Ther."},{"key":"ref66","doi-asserted-by":"publisher","first-page":"1638","DOI":"10.3390\/pathogens10121638","article-title":"\u03b2-Lactam resistance in Pseudomonas aeruginosa: current status, Future Prospects","volume":"10","author":"Glen","year":"2021","journal-title":"Pathogens"},{"key":"ref67","doi-asserted-by":"publisher","first-page":"913","DOI":"10.2165\/00003495-200363090-00005","article-title":"Panipenem\/betamipron","volume":"63","author":"Goa","year":"2003","journal-title":"Drugs"},{"key":"ref1002","doi-asserted-by":"publisher","first-page":"21550","DOI":"10.1038\/srep21550","article-title":"Appearance of \u03b2-lactam Resistance Genes in Agricultural Soils and Clinical Isolates over the 20th Century","volume":"6","author":"Graham","year":"2016","journal-title":"Sci Rep."},{"key":"ref68","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1080\/08998280.2008.11928422","article-title":"Doripenem (Doribax): the newest addition to the carbapenems","volume":"21","author":"Greer","year":"2008","journal-title":"Proc. (Bayl. Univ. Med. Cent)."},{"key":"ref69","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/B978-1-4160-2591-7.10200-0","article-title":"Chapter 200- miscellaneous antibiotics","volume-title":"Small animal critical care medicine","author":"Groman","year":"2009"},{"key":"ref70","doi-asserted-by":"publisher","first-page":"993430","DOI":"10.3389\/fmicb.2022.993430","article-title":"Molecular docking and proteomics reveals the synergistic antibacterial mechanism of theaflavin with \u03b2-lactam antibiotics against MRSA","volume":"13","author":"Guan","year":"2022","journal-title":"Front. Microbiol."},{"key":"ref71","doi-asserted-by":"publisher","first-page":"1","DOI":"10.7164\/antibiotics.41.1","article-title":"MM 42842, a new member of the monobactam family produced by pseudomonas cocovenenans. I. Identification of the producing organism","volume":"41","author":"Gwynn","year":"1988","journal-title":"J. Antibiot. (Tokyo)"},{"key":"ref72","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.mib.2016.06.008","article-title":"Antimicrobial photodynamic inactivation: a bright new technique to kill resistant microbes","volume":"33","author":"Hamblin","year":"2016","journal-title":"Curr. Opin. Microbiol."},{"key":"ref73","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1093\/jac\/44.6.729","article-title":"Beta-lactams: variations on a chemical theme, with some surprising biological results","volume":"44","author":"Hamilton-Miller","year":"1999","journal-title":"J. Antimicrob. Chemother."},{"key":"ref74","doi-asserted-by":"publisher","first-page":"e00843","DOI":"10.1128\/AAC.00843-20","article-title":"CRISPR-Cas9-mediated Carbapenemase gene and Plasmid curing in Carbapenem-resistant Enterobacteriaceae","volume":"64","author":"Hao","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref75","doi-asserted-by":"publisher","first-page":"3682","DOI":"10.1021\/acs.jmedchem.5b00127","article-title":"Discovery of a cyclic Boronic acid \u03b2-lactamase inhibitor (RPX7009) with utility vs class A serine Carbapenemases","volume":"58","author":"Hecker","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref76","doi-asserted-by":"publisher","first-page":"E3745","DOI":"10.1073\/pnas.1601368113","article-title":"Cross-class metallo-\u03b2-lactamase inhibition by bisthiazolidines reveals multiple binding modes","volume":"113","author":"Hinchliffe","year":"2016","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref77","doi-asserted-by":"publisher","first-page":"9898","DOI":"10.1021\/acsami.5b01954","article-title":"Inhibiting the VIM-2 Metallo-\u03b2-lactamase by graphene oxide and carbon nanotubes","volume":"7","author":"Huang","year":"2015","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref78","doi-asserted-by":"publisher","first-page":"596","DOI":"10.3390\/antibiotics9090596","article-title":"Identification of the PA1113 gene product as an ABC transporter involved in the uptake of Carbenicillin in Pseudomonas aeruginosa PAO1","volume":"9","author":"Hulen","year":"2020","journal-title":"Antibiotics (Basel)."},{"key":"ref79","doi-asserted-by":"publisher","first-page":"e0246571","DOI":"10.1371\/journal.pone.0246571","article-title":"Antimicrobial resistance and interspecies gene transfer in campylobacter coli and campylobacter jejuni isolated from food animals, poultry processing, and retail meat in North Carolina, 2018\u20132019","volume":"16","author":"Hull","year":"2021","journal-title":"PLoS One"},{"key":"ref80","doi-asserted-by":"publisher","first-page":"S397","DOI":"10.1093\/cid\/cir153","article-title":"Combating antimicrobial resistance: policy recommendations to save lives","volume":"52","year":"2011","journal-title":"Clin. Infect. Dis."},{"key":"ref81","doi-asserted-by":"publisher","first-page":"942","DOI":"10.1128\/AAC.22.6.942","article-title":"Role of porin proteins OmpF and OmpC in the permeation of beta-lactams","volume":"22","author":"Jaffe","year":"1982","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref82","doi-asserted-by":"publisher","first-page":"263","DOI":"10.4103\/ijmr.ijmr_199_18","article-title":"Current antibiotic use in the treatment of enteric fever in children","volume":"149","author":"Kapil","year":"2019","journal-title":"Indian J. Med. Res."},{"key":"ref83","doi-asserted-by":"publisher","first-page":"e01432","DOI":"10.1128\/AAC.01432-20","article-title":"Activity of WCK 5222 (Cefepime-Zidebactam) against worldwide collected gram-negative bacilli not susceptible to Carbapenems","volume":"64","author":"Karlowsky","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref84","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.3389\/fmicb.2018.01011","article-title":"Trans-Cinnamaldehyde and eugenol increase Acinetobacter baumannii sensitivity to Beta-lactam antibiotics","volume":"9","author":"Karumathil","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref85","doi-asserted-by":"publisher","first-page":"e0251594","DOI":"10.1371\/journal.pone.0251594","article-title":"\u03b2-Lactam resistance associated with \u03b2-lactamase production and porin alteration in clinical isolates of E. coli and K. pneumoniae","volume":"16","author":"Khalifa","year":"2021","journal-title":"PLoS One"},{"key":"ref86","doi-asserted-by":"publisher","first-page":"1263","DOI":"10.1093\/jac\/dkr106","article-title":"Characterization of IncF plasmids carrying the blaCTX-M-14 gene in clinical isolates of Escherichia coli from Korea","volume":"66","author":"Kim","year":"2011","journal-title":"J. Antimicrob. Chemother."},{"key":"ref87","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1016\/j.bmcl.2018.01.028","article-title":"Potentiation of the activity of \u03b2-lactam antibiotics by farnesol and its derivatives","volume":"28","author":"Kim","year":"2018","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref88","doi-asserted-by":"publisher","first-page":"2822","DOI":"10.3390\/ijms21082822","article-title":"The importance of Porins and \u03b2-lactamase in outer membrane vesicles on the hydrolysis of \u03b2-lactam antibiotics","volume":"21","author":"Kim","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"ref89","doi-asserted-by":"publisher","first-page":"e82814","DOI":"10.1371\/journal.pone.0082814","article-title":"The mechanism of heterogeneous beta-lactam resistance in MRSA: key role of the stringent stress response","volume":"8","author":"Kim","year":"2013","journal-title":"PLoS One"},{"key":"ref90","doi-asserted-by":"publisher","first-page":"16529","DOI":"10.1073\/pnas.1904700116","article-title":"A selective membrane-targeting repurposed antibiotic with activity against persistent methicillin-resistant Staphylococcus aureus","volume":"116","author":"Kim","year":"2019","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref91","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1038\/nature13445","article-title":"Aspergillomarasmine A overcomes metallo-\u03b2-lactamase antibiotic resistance","volume":"510","author":"King","year":"2014","journal-title":"Nature"},{"key":"ref92","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1128\/AAC.01540-15","article-title":"Impact of a Cross-kingdom signaling molecule of Candida albicans on Acinetobacter baumannii physiology","volume":"60","author":"Kostoulias","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref93","doi-asserted-by":"publisher","first-page":"9596","DOI":"10.3390\/ijms22179596","article-title":"Metal and metal oxide nanoparticle as a novel antibiotic carrier for the direct delivery of antibiotics","volume":"22","author":"Kotrange","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"ref94","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2019\/7601847","article-title":"Current perspectives on treatment of gram-positive infections in India: what is the way forward?","volume":"2019","author":"Kulkarni","year":"2019","journal-title":"Interdiscip. Perspect. Infect. Dis."},{"key":"ref95","doi-asserted-by":"publisher","first-page":"fnz 118","DOI":"10.1093\/femsle\/fnz118","article-title":"Bio-surfactin stabilised silver nanoparticles exert inhibitory effect over new-Delhi metallo-beta-lactamases (NDMs) and the cells harbouring NDMs","volume":"366","author":"Kumar","year":"2019","journal-title":"FEMS Microbiol. Lett."},{"key":"ref96","doi-asserted-by":"publisher","first-page":"3861","DOI":"10.1002\/anie.200500835","article-title":"Irreversible inhibition of Metallo-\u03b2-lactamase (IMP-1) by 3-(3-Mercaptopropionylsulfanyl) propionic acid Pentafluorophenyl Ester","volume":"44","author":"Kurosaki","year":"2005","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref97","doi-asserted-by":"publisher","first-page":"301","DOI":"10.3947\/ic.2017.49.4.301","article-title":"Clinical guidelines for the antibiotic treatment for community-acquired skin and soft tissue infection","volume":"49","author":"Kwak","year":"2017","journal-title":"Infect. Chemother"},{"key":"ref98","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1021\/acsmedchemlett.7b00200","article-title":"Synthetic antibacterial peptide exhibits synergy with oxacillin against MRSA","volume":"8","author":"Lainson","year":"2017","journal-title":"ACS Med. Chem. Lett."},{"key":"ref99","doi-asserted-by":"publisher","first-page":"e60666","DOI":"10.1371\/journal.pone.0060666","article-title":"The efflux inhibitor phenylalanine-arginine beta-naphthylamide (PA\u03b2N) permeabilizes the outer membrane of gram-negative bacteria","volume":"8","author":"Lamers","year":"2013","journal-title":"PLoS One"},{"key":"ref100","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1093\/femsre\/fuz014","article-title":"Antibiotic resistance breakers: current approaches and future directions","volume":"43","author":"Laws","year":"2019","journal-title":"FEMS Microbiol. Rev."},{"key":"ref101","doi-asserted-by":"publisher","first-page":"816657","DOI":"10.3389\/fcimb.2021.816657","article-title":"Impact of PBP4 alterations on \u03b2-lactam resistance and Ceftobiprole non-susceptibility among enterococcus faecalis clinical isolates","volume":"11","author":"Lazzaro","year":"2022","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref102","doi-asserted-by":"publisher","first-page":"e01648","DOI":"10.1128\/AAC.01648-19","article-title":"WCK 5222 (Cefepime\/Zidebactam) Pharmacodynamic target analysis against Metallo-\u03b2-lactamase producing in the neutropenic mouse pneumonia model","volume":"63","author":"Lepak","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref103","doi-asserted-by":"publisher","first-page":"116128","DOI":"10.1016\/j.bmc.2021.116128","article-title":"Dipyridyl-substituted thiosemicarbazone as a potent broad-spectrum inhibitor of metallo-\u03b2-lactamases","volume":"38","author":"Li","year":"2021","journal-title":"Bioorg. Med. Chem."},{"key":"ref104","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1093\/jac\/dkr017","article-title":"Artesunate enhances the antibacterial effect of {beta}-lactam antibiotics against Escherichia coli by increasing antibiotic accumulation via inhibition of the multidrug efflux pump system AcrAB-TolC","volume":"66","author":"Li","year":"2011","journal-title":"J. Antimicrob. Chemother."},{"key":"ref105","doi-asserted-by":"publisher","first-page":"e0168060","DOI":"10.1371\/journal.pone.0168060","article-title":"Structure-function analysis of the transmembrane protein AmpG from Pseudomonas aeruginosa","volume":"11","author":"Li","year":"2016","journal-title":"PLoS One"},{"key":"ref106","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1186\/s13756-019-0489-3","article-title":"The nature and epidemiology of OqxAB, a multidrug efflux pump","volume":"8","author":"Li","year":"2019","journal-title":"Antimicrob. Resist. Infect. Control"},{"key":"ref107","doi-asserted-by":"publisher","first-page":"197","DOI":"10.3390\/ijms23010197","article-title":"Enzyme inhibitors: the best strategy to tackle superbug NDM-1 and its variants","volume":"23","author":"Li","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"ref108","doi-asserted-by":"publisher","first-page":"2789","DOI":"10.1021\/acs.jmedchem.9b01518","article-title":"Discovery of Taniborbactam (VNRX-5133): a broad-Spectrum serine-and Metallo-\u03b2-lactamase inhibitor for Carbapenem-resistant bacterial infections","volume":"63","author":"Liu","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref109","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1038\/s41420-018-0029-6","article-title":"Magnolol restores the activity of Meropenem against NDM-1-producing Escherichia coli by inhibiting the activity of Metallo-Beta-lactamase","volume":"4","author":"Liu","year":"2018","journal-title":"Cell Death Discov."},{"key":"ref110","doi-asserted-by":"publisher","first-page":"697180","DOI":"10.3389\/fmicb.2021.697180","article-title":"QPX 7728, an ultra-broad-Spectrum B-lactamase inhibitor for intravenous and Oral therapy: overview of biochemical and microbiological characteristics","volume":"12","author":"Lomovskaya","year":"2021","journal-title":"Front. Microbiol."},{"key":"ref111","doi-asserted-by":"publisher","first-page":"769","DOI":"10.3390\/antibiotics10070769","article-title":"Pharmacokinetics of non-\u03b2-lactam \u03b2-lactamase inhibitors","volume":"10","author":"Luci","year":"2021","journal-title":"Antibiotics (Basel)."},{"key":"ref112","doi-asserted-by":"publisher","first-page":"e2117283119","DOI":"10.1073\/pnas.2117283119","article-title":"Human defensin-inspired discovery of peptidomimetic antibiotics","volume":"119","author":"Luo","year":"2022","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref113","doi-asserted-by":"publisher","first-page":"3517","DOI":"10.1038\/s41467-019-11503-3","article-title":"The antimicrobial peptide thanatin disrupts the bacterial outer membrane and inactivates the NDM-1 metallo-\u03b2-lactamase","volume":"10","author":"Ma","year":"2019","journal-title":"Nat. Commun."},{"key":"ref114","doi-asserted-by":"publisher","first-page":"e02229","DOI":"10.1128\/AAC.02229-19","article-title":"Safety and pharmacokinetic characterization of Nacubactam, a novel \u03b2-lactamase inhibitor, alone and in combination with Meropenem, in healthy volunteers","volume":"64","author":"Mallalieu","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref115","doi-asserted-by":"publisher","first-page":"6015","DOI":"10.1038\/srep06015","article-title":"Controlling resistant bacteria with a novel class of \u03b2-lactamase inhibitor peptides: from rational design to in vivo analyses","volume":"4","author":"Mandal","year":"2014","journal-title":"Sci. Rep."},{"key":"ref116","doi-asserted-by":"publisher","first-page":"2838","DOI":"10.1021\/acs.jcim.0c00352","article-title":"Machine learning algorithm identifies an antibiotic vocabulary for permeating gram-negative bacteria","volume":"60","author":"Mansbach","year":"2020","journal-title":"J. Chem. Inf. Model."},{"key":"ref117","doi-asserted-by":"crossref","DOI":"10.5772\/intechopen.87316","volume-title":"Antimicrobial resistance: a one health perspective","author":"Mares","year":"2021"},{"key":"ref118","doi-asserted-by":"publisher","first-page":"3322","DOI":"10.1128\/AAC.44.12.3322-3327.2000","article-title":"Substrate specificities of Mex AB-OprM, MexCD-OprJ, and MexXY-oprM efflux pumps in Pseudomonas aeruginosa","volume":"44","author":"Masuda","year":"2000","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref119","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1007\/s11274-021-03070-x","article-title":"Nanoparticles as therapeutic options for treating multidrug-resistant bacteria: research progress, challenges, and prospects","volume":"37","author":"Mba","year":"2021","journal-title":"World J. Microbiol. Biotechnol."},{"key":"ref120","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1186\/s43088-021-00147-2","article-title":"Combination of silver nanoparticles with ineffective antibiotics against extended spectrum beta-lactamases producing isolates at Alexandria Main university hospital, Egypt","volume":"10","author":"Mohammed","year":"2021","journal-title":"Beni-Suef Univ. J. Basic Appl. Sci."},{"key":"ref121","doi-asserted-by":"publisher","first-page":"2152","DOI":"10.1021\/acsinfecdis.1c00147","article-title":"Antibiotic potentiation in multidrug-resistant gram-negative pathogenic bacteria by a synthetic Peptidomimetic","volume":"7","author":"Mood","year":"2021","journal-title":"ACS Infect. Dis."},{"key":"ref122","doi-asserted-by":"publisher","first-page":"909","DOI":"10.3389\/fmicb.2020.00909","article-title":"Thanatin impairs lipopolysaccharide transport complex assembly by targeting LptC\u2013LptA interaction and decreasing LptA stability","volume":"11","author":"Moura","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref123","doi-asserted-by":"publisher","first-page":"e02529","DOI":"10.1128\/AAC.02529-16","article-title":"WCK 5107 (Zidebactam) and WCK 5153 are novel inhibitors of PBP2 showing potent \u201c\u03b2-lactam enhancer\u201d activity against Pseudomonas aeruginosa, including multidrug-resistant Metallo-\u03b2-lactamase-producing high-risk clones","volume":"61","author":"Moya","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref124","doi-asserted-by":"publisher","first-page":"e1000353","DOI":"10.1371\/journal.ppat.1000353","article-title":"\u03b2-Lactam resistance response triggered by inactivation of a nonessential penicillin-binding protein","volume":"5","author":"Moya","year":"2009","journal-title":"PLoS Pathog."},{"key":"ref125","doi-asserted-by":"publisher","first-page":"001","DOI":"10.3855\/jidc.9486","article-title":"Role of efflux pump and OprD porin expression in carbapenem resistance of Pseudomonas aeruginosa clinical isolates","volume":"12","author":"Muderris","year":"2018","journal-title":"J. Infect. Dev. Ctries."},{"key":"ref126","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.VMBF-0016-2015","article-title":"Mechanisms of antibiotic resistance","volume":"4","author":"Munita","year":"2016","journal-title":"Microbiol. Spectr."},{"key":"ref127","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1016\/S1473-3099(13)70190-7","article-title":"Clinical epidemiology of the global expansion of Klebsiella pneumoniae carbapenemases","volume":"13","author":"Munoz-Price","year":"2013","journal-title":"Lancet Infect. Dis."},{"key":"ref128","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1080\/14756366.2017.1344235","article-title":"Beta-lactamase database (BLDB) \u2013 structure and function","volume":"32","author":"Naas","year":"2017","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"ref129","doi-asserted-by":"publisher","first-page":"37","DOI":"10.4236\/aim.2021.111004","article-title":"An overview of extended Spectrum Beta lactamases and Metallo Beta lactamases","volume":"11","author":"Nagshetty","year":"2021","journal-title":"Adv. Microbiol."},{"key":"ref130","doi-asserted-by":"publisher","first-page":"106097","DOI":"10.1016\/j.ijantimicag.2020.106097","article-title":"Adaptive laboratory evolution of vibrio cholerae to doxycycline associated with spontaneous mutation","volume":"56","author":"Narendrakumar","year":"2020","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref131","doi-asserted-by":"publisher","first-page":"1245","DOI":"10.12669\/pjms.295.3885","article-title":"Nosocomial Acinetobacter baumannii infections and changing antibiotic resistance","volume":"29","author":"Necati Hakyemez","year":"2013","journal-title":"Pak. J. Med. Sci."},{"key":"ref132","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/0002-9343(85)90254-2","article-title":"Relation of structural properties of beta-lactam antibiotics to antibacterial activity","volume":"79","author":"Neu","year":"1985","journal-title":"Am. J. Med."},{"key":"ref133","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1099\/jmm.0.081869-0","article-title":"Imipenem heteroresistance: high prevalence among Enterobacteriaceae Klebsiella pneumoniae carbapenemase producers","volume":"64","author":"Nodari","year":"2015","journal-title":"J. Med. Microbiol."},{"key":"ref134","first-page":"182","article-title":"The pleuromutilin antibiotics: a new class for human use","volume":"11","author":"Novak","year":"2010","journal-title":"Curr. Opin. Investig. Drugs"},{"key":"ref135","volume-title":"Challenges to tackling antimicrobial resistance economic and policy responses: economic and policy responses","year":"2020"},{"key":"ref136","doi-asserted-by":"publisher","first-page":"e00181","DOI":"10.1128\/cmr.00181-19","article-title":"Antimicrobial resistance in ESKAPE pathogens","volume":"33","author":"Oliveira","year":"2020","journal-title":"Clin. Microbiol. Rev."},{"key":"ref137","doi-asserted-by":"publisher","first-page":"e01207","DOI":"10.1128\/AAC.01207-19","article-title":"Mechanism-of-action classification of antibiotics by global transcriptome profiling","volume":"64","author":"O'Rourke","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref138","doi-asserted-by":"publisher","first-page":"4221","DOI":"10.1073\/pnas.1501124112","article-title":"Multiplexed metagenome mining using short DNA sequence tags facilitates targeted discovery of epoxyketone proteasome inhibitors","volume":"112","author":"Owen","year":"2015","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref139","doi-asserted-by":"publisher","DOI":"10.1002\/047120918x.emb0150","article-title":"Beta-Lactamases","author":"Page","year":"2002","journal-title":"Encycl. Mol. Biol."},{"key":"ref140","doi-asserted-by":"publisher","first-page":"8593","DOI":"10.1128\/jb.01163-07","article-title":"Phenotypic characterization of pore mutants of the vibrio cholerae Porin OmpU","volume":"189","author":"Pagel","year":"2007","journal-title":"J. Bacteriol."},{"key":"ref141","doi-asserted-by":"publisher","first-page":"2169","DOI":"10.1080\/14656566.2019.1660772","article-title":"The latest advances in \u03b2-lactam\/\u03b2-lactamase inhibitor combinations for the treatment of gram-negative bacterial infections","volume":"20","author":"Papp-Wallace","year":"2019","journal-title":"Expert. Opin. Pharmacother."},{"key":"ref142","doi-asserted-by":"publisher","first-page":"e00105","DOI":"10.1128\/AAC.00105-19","article-title":"Beyond piperacillin-Tazobactam: Cefepime and AAI101 as a potent \u03b2-lactam-\u03b2-lactamase inhibitor combination","volume":"63","author":"Papp-Wallace","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref143","doi-asserted-by":"publisher","first-page":"4943","DOI":"10.1128\/AAC.00296-11","article-title":"Carbapenems: past, present, and future","volume":"55","author":"Papp-Wallace","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref144","doi-asserted-by":"publisher","first-page":"e0244967","DOI":"10.1371\/journal.pone.0244967","article-title":"Discovery of beta-lactamase CMY-10 inhibitors for combination therapy against multi-drug resistant Enterobacteriaceae","volume":"16","author":"Parvaiz","year":"2021","journal-title":"PLoS One"},{"key":"ref145","doi-asserted-by":"publisher","first-page":"CD003344","DOI":"10.1002\/14651858.cd003344.pub2","article-title":"Beta lactam antibiotic monotherapy versus beta lactam-aminoglycoside antibiotic combination therapy for sepsis","volume":"2014","author":"Paul","year":"2006","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref146","doi-asserted-by":"publisher","first-page":"2221","DOI":"10.2165\/00003495-200262150-00005","article-title":"Biapenem","volume":"62","author":"Perry","year":"2002","journal-title":"Drugs"},{"key":"ref147","doi-asserted-by":"publisher","first-page":"e00102","DOI":"10.1128\/CMR.00102-19","article-title":"The global ascendency of OXA-48-type Carbapenemases","volume":"33","author":"Pitout","year":"2019","journal-title":"Clin. Microbiol. Rev."},{"key":"ref148","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1128\/aac.01512-08","article-title":"Diversity, epidemiology, and genetics of class D \u03b2-lactamases","volume":"54","author":"Poirel","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref149","doi-asserted-by":"publisher","first-page":"1442","DOI":"10.1128\/aac.50.4.1442-1448.2006","article-title":"Genetic structures at the origin of acquisition and expression of the Carbapenem-hydrolyzing Oxacillinase gene Bla OXA-58 in Acinetobacter baumannii","volume":"50","author":"Poirel","year":"2006","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref150","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1186\/s12941-017-0248-3","article-title":"Molecular characterization of \u03b2-lactamase genes in clinical isolates of carbapenem-resistant Acinetobacter baumannii","volume":"16","author":"Raible","year":"2017","journal-title":"Ann. Clin. Microbiol. Antimicrob."},{"key":"ref151","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1128\/AAC.11.5.852","article-title":"Clavulanic acid: a beta-lactamase-inhibiting beta-lactam from Streptomyces clavuligerus","volume":"11","author":"Reading","year":"1977","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref152","doi-asserted-by":"publisher","first-page":"e3000805","DOI":"10.1371\/journal.pbio.3000805","article-title":"Combining antibiotics with antivirulence compounds can have synergistic effects and reverse selection for antibiotic resistance in Pseudomonas aeruginosa","volume":"18","author":"Rezzoagli","year":"2020","journal-title":"PLoS Biol."},{"key":"ref153","doi-asserted-by":"publisher","first-page":"3118","DOI":"10.1093\/jac\/dkac292","article-title":"Double-, single-and none-carbapenem-containing regimens for the treatment of carbapenem-resistant Enterobacterales (CRE) bloodstream infections: a retrospective cohort","volume":"77","author":"Rigatto","year":"2022","journal-title":"J. Antimicrob. Chemother."},{"key":"ref154","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1016\/j.ijantimicag.2014.02.019","article-title":"Chromosomal location of blaCTX-M genes in clinical isolates of Escherichia coli from Germany, the Netherlands and the UK","volume":"43","author":"Rodr\u00edguez","year":"2014","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref155","doi-asserted-by":"publisher","first-page":"S727","DOI":"10.1093\/clinids\/13.supplement_9.s727","article-title":"Evolution of \u03b2-lactamase inhibitors","volume":"13","author":"Rolinson","year":"1991","journal-title":"Clin. Infect. Dis."},{"key":"ref156","doi-asserted-by":"publisher","first-page":"e01745","DOI":"10.1128\/AAC.01745-16","article-title":"Classical \u03b2-lactamase inhibitors potentiate the activity of Daptomycin against methicillin-resistant Staphylococcus aureus and Colistin against Acinetobacter baumannii","volume":"61","author":"Sakoulas","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref157","doi-asserted-by":"publisher","first-page":"2390","DOI":"10.1038\/s41598-021-82009-6","article-title":"Discovery of potential inhibitors against New Delhi metallo-\u03b2-lactamase-1 from natural compounds: in silico-based methods","volume":"11","author":"Salari-Jazi","year":"2021","journal-title":"Sci. Rep."},{"key":"ref158","doi-asserted-by":"publisher","first-page":"585398","DOI":"10.3389\/fmicb.2020.585398","article-title":"Discovery of novel biosynthetic gene cluster diversity from a soil metagenomic library","volume":"11","author":"Santana-Pereira","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref159","doi-asserted-by":"publisher","first-page":"6870","DOI":"10.1128\/aac.03775-14","article-title":"Random mutagenesis of the multidrug transporter AcrB from Escherichia coli for identification of putative target residues of efflux pump inhibitors","volume":"58","author":"Schuster","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref160","doi-asserted-by":"publisher","first-page":"1630","DOI":"10.1110\/ps.051355705","article-title":"The prokaryotic enzyme DsbB may share key structural features with eukaryotic disulfide bond forming oxidoreductases","volume":"14","author":"Sevier","year":"2005","journal-title":"Protein Sci."},{"key":"ref161","doi-asserted-by":"publisher","first-page":"709974","DOI":"10.3389\/fmicb.2021.709974","article-title":"Durlobactam, a new Diazabicyclooctane \u03b2-lactamase inhibitor for the treatment of Acinetobacter infections in combination with Sulbactam","volume":"12","author":"Shapiro","year":"2021","journal-title":"Front. Microbiol."},{"key":"ref162","doi-asserted-by":"publisher","first-page":"337","DOI":"10.4103\/ijp.ijp_87_17","article-title":"Study of inhibitory potential and percent inhibition of oil of Syzygium aromaticum and leaves of Ocimum sanctum on ESBL enzyme from Escherichia coli in broilers of Jabalpur","volume":"51","author":"Shrivastav","year":"2019","journal-title":"Indian J. Pharmacol."},{"key":"ref163","doi-asserted-by":"publisher","first-page":"9098","DOI":"10.1038\/s41598-019-45550-z","article-title":"Dual \u03b2-lactam combination therapy for multi-drug resistant Pseudomonas aeruginosa infection: enhanced efficacy in vivo and comparison with monotherapies of penicillin-binding protein inhibition","volume":"9","author":"Siriyong","year":"2019","journal-title":"Sci. Rep."},{"key":"ref164","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1186\/s12906-017-1913-y","article-title":"Conessine as a novel inhibitor of multidrug efflux pump systems in Pseudomonas aeruginosa","volume":"17","author":"Siriyong","year":"2017","journal-title":"BMC Complement. Altern. Med."},{"key":"ref165","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1177\/1087057112474690","article-title":"Identification of a small-molecule inhibitor of bacterial AraC family activators","volume":"18","author":"Skredenske","year":"2013","journal-title":"J. Biomol. Screen."},{"key":"ref166","doi-asserted-by":"publisher","first-page":"1806","DOI":"10.1128\/AAC.02101-13","article-title":"Role of OmpA in the multidrug resistance phenotype of Acinetobacter baumannii","volume":"58","author":"Smani","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref167","doi-asserted-by":"publisher","first-page":"1300","DOI":"10.1038\/1951300a0","article-title":"Isoxazolyl Penicillins and penicillinase","volume":"195","author":"Smith","year":"1962","journal-title":"Nature"},{"key":"ref168","doi-asserted-by":"publisher","first-page":"12763","DOI":"10.1038\/s41598-020-69431-y","article-title":"Virtual screening identifies broad-spectrum \u03b2-lactamase inhibitors with activity on clinically relevant serine-and metallo-carbapenemases","volume":"10","author":"Spyrakis","year":"2020","journal-title":"Sci. Rep."},{"key":"ref169","doi-asserted-by":"publisher","first-page":"4449","DOI":"10.1128\/AAC.02284-12","article-title":"KpnEF, a new member of the Klebsiella pneumoniae cell envelope stress response regulon, is an SMR-type efflux pump involved in broad-spectrum antimicrobial resistance","volume":"57","author":"Srinivasan","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref170","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1016\/j.ijantimicag.2003.09.027","article-title":"Modulation of \u03b2-lactam resistance in Staphylococcus aureus by catechins and gallates","volume":"23","author":"Stapleton","year":"2004","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref171","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.addr.2014.04.006","article-title":"Antibiotic-containing polymers for localized, sustained drug delivery","volume":"78","author":"Stebbins","year":"2014","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref172","doi-asserted-by":"publisher","first-page":"2115","DOI":"10.1021\/acschembio.9b00618","article-title":"Metagenome driven discovery of nonribosomal peptides","volume":"14","author":"Stevenson","year":"2019","journal-title":"ACS Chem. Biol."},{"key":"ref173","doi-asserted-by":"publisher","first-page":"5057","DOI":"10.1128\/aac.00768-10","article-title":"Outbreak of Meropenem-resistant Serratia marcescens Comediated by chromosomal AmpC \u03b2-lactamase overproduction and outer membrane protein loss","volume":"54","author":"Suh","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref174","doi-asserted-by":"publisher","first-page":"578","DOI":"10.3389\/fmicb.2020.00578","article-title":"Exploring the potential of CRISPR-Cas9 under challenging conditions: facing high-copy plasmids and counteracting Beta-lactam resistance in clinical strains of Enterobacteriaceae","volume":"11","author":"Tagliaferri","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref175","doi-asserted-by":"publisher","first-page":"266","DOI":"10.3390\/antibiotics11020266","article-title":"Potentiation of \u03b2-lactams against methicillin-resistant Staphylococcus aureus (MRSA) using Octyl Gallate, a food-grade antioxidant","volume":"11","author":"Tamang","year":"2022","journal-title":"Antibiotics (Basel)."},{"key":"ref176","doi-asserted-by":"publisher","first-page":"3202","DOI":"10.1128\/AAC.00006-08","article-title":"Inhibitors of bacterial multidrug efflux pumps potentiate antimicrobial photoinactivation","volume":"52","author":"Tegos","year":"2008","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref177","doi-asserted-by":"publisher","first-page":"1366","DOI":"10.1021\/acsinfecdis.9b00459","article-title":"Small molecule carboxylates inhibit Metallo-\u03b2-lactamases and Resensitize Carbapenem-resistant bacteria to Meropenem","volume":"6","author":"Tehrani","year":"2020","journal-title":"ACS Infect. Dis."},{"key":"ref178","doi-asserted-by":"publisher","first-page":"1207","DOI":"10.7860\/jcdr\/2013\/5239.3052","article-title":"The Beta lactam antibiotics as an empirical therapy in a developing country: an update on their current status and recommendations to counter the resistance against them","volume":"7","author":"Thakuria","year":"2013","journal-title":"J. Clin. Diagn. Res."},{"key":"ref179","doi-asserted-by":"publisher","first-page":"860","DOI":"10.1021\/acsinfecdis.8b00105","article-title":"Total syntheses of Bulgecins a, B, and C and their bactericidal potentiation of the \u03b2-lactam antibiotics","volume":"4","author":"Tomoshige","year":"2018","journal-title":"ACS Infect Dis."},{"key":"ref180","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1099\/jmm.0.000248","article-title":"Clonal expansion of Escherichia coli ST38 carrying a chromosomally integrated OXA-48 carbapenemase gene","volume":"65","author":"Turton","year":"2016","journal-title":"J. Med. Microbiol."},{"key":"ref181","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/s40169-018-0208-3","article-title":"Application of metabolomics to drug discovery and understanding the mechanisms of action of medicinal plants with anti-tuberculosis activity","volume":"7","author":"Tuyiringire","year":"2018","journal-title":"Clin. Transl. Med."},{"key":"ref182","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1007\/s10068-018-0317-1","article-title":"Characterization of \u03b2-lactamase- and efflux pump-mediated multiple antibiotic resistance in salmonella typhimurium","volume":"27","author":"Uddin","year":"2018","journal-title":"Food Sci. Biotechnol."},{"key":"ref183","doi-asserted-by":"publisher","first-page":"10376","DOI":"10.1073\/pnas.0700962104","article-title":"Genome sequencing reveals complex secondary metabolome in the marine actinomycete Salinispora tropica","volume":"104","author":"Udwary","year":"2007","journal-title":"Proc. Natl. Acad. Sci."},{"key":"ref1001","doi-asserted-by":"publisher","first-page":"1273","DOI":"10.1128\/AAC.05760-11","article-title":"High-level cefixime- and ceftriaxone-resistant Neisseria gonorrhoeae in France: novel penA mosaic allele in a successful international clone causes treatment failure","volume":"56","author":"Unemo","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref184","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1111\/j.1574-6968.1995.tb07357.x","article-title":"Interaction of sulbactam, clavulanic acid and tazobactam with penicillin-binding proteins of imipenem-resistant and-susceptible Acinetobacter baumannii","volume":"125","author":"Urban","year":"1995","journal-title":"FEMS Microbiol. Lett."},{"key":"ref185","doi-asserted-by":"publisher","first-page":"249","DOI":"10.3390\/molecules24020249","article-title":"Polymyxin derivatives that sensitize gram-negative bacteria to other antibiotics","volume":"24","author":"Vaara","year":"2019","journal-title":"Molecules"},{"key":"ref186","doi-asserted-by":"publisher","first-page":"222","DOI":"10.4103\/ijmr.ijmr_2098_17","article-title":"Plasmid profiles among some ESKAPE pathogens in a tertiary care Centre in South India","volume":"149","author":"Veeraraghavan","year":"2019","journal-title":"Indian J. Med. Res."},{"key":"ref187","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.cbpa.2010.10.027","article-title":"Genome mining for ribosomally synthesized natural products","volume":"15","author":"Vel\u00e1squez","year":"2011","journal-title":"Curr. Opin. Chem. Biol."},{"key":"ref188","doi-asserted-by":"publisher","first-page":"1478","DOI":"10.1001\/jama.2020.2717","article-title":"Prevalence and outcomes of infection among patients in intensive care units in 2017","volume":"323","author":"Vincent","year":"2020","journal-title":"JAMA"},{"key":"ref189","doi-asserted-by":"publisher","first-page":"e3306","DOI":"10.1002\/psc.3306","article-title":"The effect of structural modification of antimicrobial peptides on their antimicrobial activity, hemolytic activity, and plasma stability","volume":"27","author":"Wang","year":"2021","journal-title":"J. Pept. Sci."},{"key":"ref190","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1128\/AAC.35.1.147","article-title":"Transferable imipenem resistance in Pseudomonas aeruginosa","volume":"35","author":"Watanabe","year":"1991","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref191","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1016\/j.mib.2005.08.016","article-title":"\u03b2-Lactam antibiotic resistance: a current structural perspective","volume":"8","author":"Wilke","year":"2005","journal-title":"Curr. Opin. Microbiol."},{"key":"ref192","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1128\/aac.35.6.1081","article-title":"Pharmacokinetics and tissue penetration of Tazobactam administered alone and with piperacillin","volume":"35","author":"Wise","year":"1991","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref193","volume-title":"Drug-resistant infections: A threat to our economic future","year":"2017"},{"key":"ref194","volume-title":"Antimicrobial resistance: Global report on surveillance","year":"2014"},{"key":"ref195","doi-asserted-by":"publisher","first-page":"e00115","DOI":"10.1128\/CMR.00115-18","article-title":"NDM Metallo-\u03b2-lactamases and their bacterial producers in health care settings","volume":"32","author":"Wu","year":"2019","journal-title":"Clin. Microbiol. Rev."},{"key":"ref196","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1007\/s40121-020-00286-6","article-title":"Cefiderocol: a novel agent for the management of multidrug-resistant gram-negative organisms","volume":"9","author":"Wu","year":"2020","journal-title":"Infect. Dis. Ther."},{"key":"ref197","doi-asserted-by":"publisher","first-page":"e00115-20","DOI":"10.1128\/CMR.00115-20","article-title":"New \u03b2-lactam-\u03b2-lactamase inhibitor combinations","volume":"34","author":"Yahav","year":"2020","journal-title":"Clin. Microbiol. Rev."},{"key":"ref198","doi-asserted-by":"publisher","first-page":"581001","DOI":"10.3389\/fphar.2020.581001","article-title":"Discovery of a novel natural allosteric inhibitor that targets NDM-1 against Escherichia coli","volume":"11","author":"Yang","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref199","doi-asserted-by":"publisher","first-page":"8014","DOI":"10.1039\/c7cc02774e","article-title":"Real-time activity monitoring of New Delhi metallo-\u03b2-lactamase-1 in living bacterial cells by UV-vis spectroscopy","volume":"53","author":"Yang","year":"2017","journal-title":"Chem Comm."},{"key":"ref200","doi-asserted-by":"publisher","first-page":"eaal3973","DOI":"10.1126\/scitranslmed.aal3973","article-title":"High-throughput metabolomic analysis predicts mode of action of uncharacterized antimicrobial compounds","volume":"10","author":"Zampieri","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"ref201","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/j.apsb.2020.07.005","article-title":"Discovery of thiosemicarbazone derivatives as effective New Delhi metallo-\u03b2-lactamase-1 (NDM-1) inhibitors against NDM-1 producing clinical isolates","volume":"11","author":"Zhao","year":"2021","journal-title":"Acta Pharm. Sin. B"},{"key":"ref202","doi-asserted-by":"publisher","first-page":"128","DOI":"10.3389\/fcimb.2019.00128","article-title":"Application of antimicrobial peptides of the innate immune system in combination with conventional antibiotics-a novel way to combat antibiotic resistance?","volume":"9","author":"Zharkova","year":"2019","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref203","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1186\/s13756-019-0590-7","article-title":"Economic burden of antibiotic resistance in ESKAPE organisms: a systematic review","volume":"8","author":"Zhen","year":"2019","journal-title":"Antimicrob. Resist. Infect. Control"}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2022.1092556\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T23:59:06Z","timestamp":1678406346000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2022.1092556\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,10]]},"references-count":206,"alternative-id":["10.3389\/fmicb.2022.1092556"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2022.1092556","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,10]]},"article-number":"1092556"}}