{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T03:55:20Z","timestamp":1793850920026,"version":"4.6.1"},"reference-count":164,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T00:00:00Z","timestamp":1692835200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"Korean government, Ministry of Science and ICT (MSIT)","doi-asserted-by":"publisher","award":["2017M3A9E4077232"],"award-info":[{"award-number":["2017M3A9E4077232"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Kangdong Sacred Heart Hospital Research Fund","award":["2017M3A9E4077232"],"award-info":[{"award-number":["2017M3A9E4077232"]}],"id":[{"id":"https:\/\/ror.org\/05mx1gf76","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>The development of antibiotic resistance in Staphylococcus aureus, particularly in methicillin-resistant S. aureus (MRSA), has become a significant health concern worldwide. The acquired mecA gene encodes penicillin-binding protein 2a (PBP2a), which takes over the activities of endogenous PBPs and, due to its low affinity for \u03b2-lactam antibiotics, is the main determinant of MRSA. In addition to PBP2a, other genetic factors that regulate cell wall synthesis, cell signaling pathways, and metabolism are required to develop high-level \u03b2-lactam resistance in MRSA. Although several genetic factors that modulate \u03b2-lactam resistance have been identified, it remains unclear how they alter PBP2a expression and affect antibiotic resistance. This review describes the molecular determinants of \u03b2-lactam resistance in MRSA, with a focus on recent developments in our understanding of the role of mecA-encoded PBP2a and on other genetic factors that modulate the level of \u03b2-lactam resistance. Understanding the molecular determinants of \u03b2-lactam resistance can aid in developing novel strategies to combat MRSA.<\/jats:p>","DOI":"10.3390\/antibiotics12091362","type":"journal-article","created":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T10:06:48Z","timestamp":1692871608000},"page":"1362","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":170,"title":["Molecular Determinants of \u03b2-Lactam Resistance in Methicillin-Resistant Staphylococcus aureus (MRSA): An Updated Review"],"prefix":"10.3390","volume":"12","author":[{"given":"Harshad","family":"Lade","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Hallym University College of Medicine, Kangdong Sacred Heart Hospital, Seoul 05355, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6025-0341","authenticated-orcid":false,"given":"Jae-Seok","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Hallym University College of Medicine, Kangdong Sacred Heart Hospital, Seoul 05355, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1056\/NEJM199808203390806","article-title":"Staphylococcus aureus Infections","volume":"339","author":"Lowy","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"ref_2","first-page":"226","article-title":"On the antibacterial action of cultures of a penicillium, with special reference to their use in the isolation of B. influenzae","volume":"10","author":"Fleming","year":"1929","journal-title":"Br. J. Exp. Pathol."},{"key":"ref_3","unstructured":"Abraham, D.J. (2021). Burger\u2019s Medicinal Chemistry, Drug Discovery and Development, Wiley."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"dlaa114","DOI":"10.1093\/jacamr\/dlaa114","article-title":"Treatment of methicillin-resistant Staphylococcus aureus (MRSA): Updated guidelines from the UK","volume":"3","author":"Brown","year":"2021","journal-title":"JAC-Antimicrob. Resist."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e18","DOI":"10.1093\/cid\/ciq146","article-title":"Clinical Practice Guidelines by the Infectious Diseases Society of America for the Treatment of Methicillin-Resistant Staphylococcus aureus Infections in Adults and Children","volume":"52","author":"Liu","year":"2011","journal-title":"Clin. Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"386","DOI":"10.3181\/00379727-51-13986","article-title":"Resistance of Staphylococcus aureus to the Action of Penicillin","volume":"51","author":"Rammelkamp","year":"1942","journal-title":"Exp. Biol. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1126\/science.99.2579.452","article-title":"Extraction of a highly potent penicillin inactivator from penicillin resistant staphylococci","volume":"99","author":"Kirby","year":"1944","journal-title":"Science"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1038\/146837a0","article-title":"An enzyme from bacteria able to destroy penicillin","volume":"146","author":"Abraham","year":"1940","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1136\/bmj.2.5200.690","article-title":"A New Penicillin (BRL 1241) Active Against Penicillin-resistant Staphylococci","volume":"2","author":"Knox","year":"1960","journal-title":"BMJ"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1136\/bmj.1.5219.124-a","article-title":"\u201cCelbenin\u201d\u2014resistant Staphylococci","volume":"1","author":"Jevons","year":"1961","journal-title":"Br. Med. J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1186\/s13059-017-1252-9","article-title":"Methicillin-resistant Staphylococcus aureus emerged long before the introduction of methicillin into clinical practice","volume":"18","author":"Harkins","year":"2017","journal-title":"Genome Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1128\/jb.158.2.513-516.1984","article-title":"Low-affinity penicillin-binding protein associated with beta-lactam resistance in Staphylococcus aureus","volume":"158","author":"Hartman","year":"1984","journal-title":"J. Bacteriol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1128\/AAC.28.3.397","article-title":"Role of an altered penicillin-binding protein in methicillin- and cephem-resistant Staphylococcus aureus","volume":"28","author":"Utsui","year":"1985","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1128\/jb.167.3.975-980.1986","article-title":"Molecular cloning of the gene of a penicillin-binding protein supposed to cause high resistance to beta-lactam antibiotics in Staphylococcus aureus","volume":"167","author":"Matsuhashi","year":"1986","journal-title":"J. Bacteriol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/s41579-018-0147-4","article-title":"Methicillin-resistant Staphylococcus aureus: An overview of basic and clinical research","volume":"17","author":"Turner","year":"2019","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1056\/NEJMp0804651","article-title":"Antibiotic-Resistant Bugs in the 21st Century\u2014A Clinical Super-Challenge","volume":"360","author":"Arias","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e00020-18","DOI":"10.1128\/CMR.00020-18","article-title":"Methicillin-Resistant Staphylococcus aureus: Molecular Characterization, Evolution, and Epidemiology","volume":"31","author":"Lakhundi","year":"2018","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1086\/646432","article-title":"Methicillin-Resistant Staphylococcus aureus in U.S. Hospitals, 1975\u20131991","volume":"13","author":"Panlilio","year":"1992","journal-title":"Infect. Control Hosp. Epidemiol."},{"key":"ref_19","first-page":"1970","article-title":"National Burden of Invasive Methicillin-Resistant Staphylococcus aureus Infections, United States, 2011","volume":"173","author":"Dantes","year":"2013","journal-title":"JAMA Intern. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.3201\/eid1312.070629","article-title":"Hospitalizations and Deaths Caused by Methicillin-Resistant Staphylococcus aureus, United States, 1999\u20132005","volume":"13","author":"Klein","year":"2007","journal-title":"Emerg. Infect. Dis."},{"key":"ref_21","unstructured":"European Centre for Disease Prevention and Control (2022). Assessing the Health Burden of Infections with Antibiotic-Resistant Bacteria in the EU\/EEA, 2016\u20132020."},{"key":"ref_22","unstructured":"Centers for Disease Control and Prevention (2019). Antibiotic Resistance Threats in the United States, 2019."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1056\/NEJMoa1914433","article-title":"Multidrug-Resistant Bacterial Infections in U.S. Hospitalized Patients, 2012\u20132017","volume":"382","author":"Jernigan","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_24","unstructured":"Centers for Disease Control and Prevention (2022). COVID-19: U.S. Impact on Antimicrobial Resistance, Special Report 2022."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/S0140-6736(21)02724-0","article-title":"Global burden of bacterial antimicrobial resistance in 2019: A systematic analysis","volume":"399","author":"Murray","year":"2022","journal-title":"Lancet"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Kim, C., Mwangi, M., Chung, M., Milheir\u00e7o, C., de Lencastre, H., and Tomasz, A. (2013). The Mechanism of Heterogeneous Beta-Lactam Resistance in MRSA: Key Role of the Stringent Stress Response. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0082814"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1146\/annurev-biochem-060614-034516","article-title":"Mechanisms of Methicillin Resistance in Staphylococcus aureus","volume":"84","author":"Peacock","year":"2015","journal-title":"Annu. Rev. Biochem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1128\/AAC.38.4.724","article-title":"Mechanisms of heteroresistance in methicillin-resistant Staphylococcus aureus","volume":"38","author":"Ryffel","year":"1994","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1128\/AAC.46.1.24-30.2002","article-title":"Conversion of Oxacillin-Resistant Staphylococci from Heterotypic to Homotypic Resistance Expression","volume":"46","author":"Finan","year":"2002","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e0086917","DOI":"10.1128\/AAC.00869-17","article-title":"Tandem Amplification of the Staphylococcal Cassette Chromosome mec Element Can Drive High-Level Methicillin Resistance in Methicillin-Resistant Staphylococcus aureus","volume":"61","author":"Gallagher","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1128\/AAC.44.6.1549-1555.2000","article-title":"A New Class of Genetic Element, Staphylococcus Cassette Chromosome mec, Encodes Methicillin Resistance in Staphylococcus aureus","volume":"44","author":"Katayama","year":"2000","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/0014-5793(92)80039-J","article-title":"Molecular cloning and nucleotide sequence determination of the regulator region of mecA gene in methicillin-resistant Staphylococcus aureus (MRSA)","volume":"298","author":"Hiramatsu","year":"1992","journal-title":"FEBS Lett."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1074\/jbc.M112.385138","article-title":"Characterization of the Staphylococcus aureus rRNA Methyltransferase Encoded by orfX, the Gene Containing the Staphylococcal Chromosome Cassette mec (SCCmec) Insertion Site","volume":"288","author":"Boundy","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1128\/AAC.43.6.1449","article-title":"Cloning and Nucleotide Sequence Determination of the Entire mec DNA of Pre-Methicillin-Resistant Staphylococcus aureus N315","volume":"43","author":"Ito","year":"1999","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/S1473-3099(11)70126-8","article-title":"Meticillin-resistant Staphylococcus aureus with a novel mecA homologue in human and bovine populations in the UK and Denmark: A descriptive study","volume":"11","author":"Holden","year":"2011","journal-title":"Lancet Infect. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3791","DOI":"10.1128\/AAC.02731-13","article-title":"The mecA Homolog mecC Confers Resistance against \u03b2-Lactams in Staphylococcus aureus Irrespective of the Genetic Strain Background","volume":"58","author":"Ballhausen","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4352","DOI":"10.1128\/AAC.00356-10","article-title":"Origin and Molecular Evolution of the Determinant of Methicillin Resistance in Staphylococci","volume":"54","author":"Tsubakishita","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1128\/JB.01549-07","article-title":"Penicillin-Binding Proteins and Cell Wall Composition in \u03b2-Lactam-Sensitive and -Resistant Strains of Staphylococcus sciuri","volume":"190","author":"Zhou","year":"2008","journal-title":"J. Bacteriol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1089\/mdr.1996.2.377","article-title":"Ubiquitous Presence of a mecA Homologue in Natural Isolates of Staphylococcus sciuri","volume":"2","author":"Couto","year":"1996","journal-title":"Microb. Drug Resist."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/j.1574-695X.2005.00009.x","article-title":"SCC mec in staphylococci: Genes on the move","volume":"46","author":"Hanssen","year":"2006","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1111\/j.1348-0421.1995.tb02239.x","article-title":"Molecular Evolution of MRSA","volume":"39","author":"Hiramatsu","year":"1995","journal-title":"Microbiol. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4961","DOI":"10.1128\/AAC.00579-09","article-title":"Classification of staphylococcal cassette chromosome mec (SCCmec): Guidelines for reporting novel SCCmec elements","volume":"53","author":"Ito","year":"2009","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Uehara, Y. (2022). Current Status of Staphylococcal Cassette Chromosome mec (SCCmec). Antibiotics, 11.","DOI":"10.3390\/antibiotics11010086"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"18033","DOI":"10.1038\/nrdp.2018.33","article-title":"Methicillin-resistant Staphylococcus aureus","volume":"4","author":"Lee","year":"2018","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1128\/AAC.45.5.1323-1336.2001","article-title":"Structural Comparison of Three Types of Staphylococcal Cassette Chromosome mec Integrated in the Chromosome in Methicillin-Resistant Staphylococcus aureus","volume":"45","author":"Ito","year":"2001","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1016\/S0140-6736(00)04832-7","article-title":"Evidence for in-vivo transfer of mecA DNA between strains of Staphylococcus aureus","volume":"357","author":"Wielders","year":"2001","journal-title":"Lancet"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Bloemendaal, A.L.A., Brouwer, E.C., and Fluit, A.C. (2010). Methicillin Resistance Transfer from Staphylocccus epidermidis to Methicillin-Susceptible Staphylococcus aureus in a Patient during Antibiotic Therapy. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0011841"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2072","DOI":"10.1128\/AAC.01539-05","article-title":"Novel mobile variants of staphylococcal cassette chromosome mec in Staphylococcus aureus","volume":"50","author":"Jansen","year":"2006","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"242","DOI":"10.3201\/eid2402.171074","article-title":"Plasmid-Encoded Transferable mecB -Mediated Methicillin Resistance in Staphylococcus aureus","volume":"24","author":"Becker","year":"2018","journal-title":"Emerg. Infect. Dis."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1038\/nrmicro2200","article-title":"Waves of resistance: Staphylococcus aureus in the antibiotic era","volume":"7","author":"Chambers","year":"2009","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"4490","DOI":"10.1016\/S0021-9258(18)34749-5","article-title":"Membrane-bound penicillinases in Gram-positive bacteria","volume":"257","author":"Nielsen","year":"1982","journal-title":"J. Biol. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3412","DOI":"10.1021\/acs.chemrev.0c01010","article-title":"\u03b2-Lactams against the Fortress of the Gram-Positive Staphylococcus aureus Bacterium","volume":"121","author":"Fisher","year":"2021","journal-title":"Chem. Rev."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"9786","DOI":"10.1073\/pnas.0402521101","article-title":"Complete genomes of two clinical Staphylococcus aureus strains: Evidence for the evolution of virulence and drug resistance","volume":"101","author":"Holden","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Wright, G.D. (2010). Q&A: Antibiotic resistance: Where does it come from and what can we do about it?. BMC Biol., 8.","DOI":"10.1186\/1741-7007-8-123"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1128\/AAC.37.5.1144","article-title":"blaI and blaR1 regulate beta-lactamase and PBP 2a production in methicillin-resistant Staphylococcus aureus","volume":"37","author":"Hackbarth","year":"1993","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1962","DOI":"10.1126\/science.1055144","article-title":"A Proteolytic Transmembrane Signaling Pathway and Resistance to \u03b2-Lactams in Staphylococci","volume":"291","author":"Zhang","year":"2001","journal-title":"Science"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1046\/j.1365-2958.1997.4051770.x","article-title":"Studies of the repressor (BlaI) of \u03b2-lactamase synthesis in Staphylococcus aureus","volume":"24","author":"Gregory","year":"1997","journal-title":"Mol. Microbiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1021\/bi500074w","article-title":"Regulation of the expression of the \u03b2-lactam antibiotic-resistance determinants in methicillin-resistant Staphylococcus aureus (MRSA)","volume":"53","author":"Llarrull","year":"2014","journal-title":"Biochemistry"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1126\/science.3107125","article-title":"Bacterial Resistance to \u03b2-Lactam Antibiotics: Crystal Structure of \u03b2-Lactamase from Staphylococcus aureus PC1 at 2.5 \u00c5 Resolution","volume":"236","author":"Herzberg","year":"1987","journal-title":"Science"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/s41586-022-05583-3","article-title":"Structural basis of broad-spectrum \u03b2-lactam resistance in Staphylococcus aureus","volume":"613","author":"Alexander","year":"2023","journal-title":"Nature"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1042\/bj0940584","article-title":"Wild-type variants of exopenicillinase from Staphylococcus aureus","volume":"94","author":"Richmond","year":"1965","journal-title":"Biochem. J."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1128\/AAC.36.2.440","article-title":"Characterization of four beta-lactamases produced by Staphylococcus aureus","volume":"36","author":"Zygmunt","year":"1992","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1093\/infdis\/159.1.103","article-title":"Differentiation of -Lactamase Variants of Staphylococcus aureus by Substrate Hydrolysis Profiles","volume":"159","author":"Kernodle","year":"1989","journal-title":"J. Infect. Dis."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1128\/AAC.34.3.420","article-title":"Use of extracts versus whole-cell bacterial suspensions in the identification of Staphylococcus aureus beta-lactamase variants","volume":"34","author":"Kernodle","year":"1990","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/nrmicro2677","article-title":"From the regulation of peptidoglycan synthesis to bacterial growth and morphology","volume":"10","author":"Typas","year":"2012","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1038\/s41586-020-2236-6","article-title":"The architecture of the Gram-positive bacterial cell wall","volume":"582","author":"Burns","year":"2020","journal-title":"Nature"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.ijmm.2009.10.005","article-title":"An oldie but a goodie\u2014cell wall biosynthesis as antibiotic target pathway","volume":"300","author":"Schneider","year":"2010","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1038\/nrmicro3088","article-title":"How to get (a)round: Mechanisms controlling growth and division of coccoid bacteria","volume":"11","author":"Pinho","year":"2013","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3525","DOI":"10.1128\/JB.00044-07","article-title":"Role of PBP1 in Cell Division of Staphylococcus aureus","volume":"189","author":"Pereira","year":"2007","journal-title":"J. Bacteriol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"18991","DOI":"10.1073\/pnas.1004304107","article-title":"Teichoic acids are temporal and spatial regulators of peptidoglycan cross-linking in Staphylococcus aureus","volume":"107","author":"Atilano","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1046\/j.1365-2958.2003.03719.x","article-title":"Dispersed mode of Staphylococcus aureus cell wall synthesis in the absence of the division machinery","volume":"50","author":"Pinho","year":"2003","journal-title":"Mol. Microbiol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1126\/science.1136611","article-title":"Structural insight into the transglycosylation step of bacterial cell-wall biosynthesis","volume":"315","author":"Lovering","year":"2007","journal-title":"Science"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2549","DOI":"10.1128\/JB.01474-10","article-title":"Monofunctional Transglycosylases Are Not Essential for Staphylococcus aureus Cell Wall Synthesis","volume":"193","author":"Reed","year":"2011","journal-title":"J. Bacteriol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e0066922","DOI":"10.1128\/mbio.00669-22","article-title":"Penicillin-Binding Protein 1 (PBP1) of Staphylococcus aureus Has Multiple Essential Functions in Cell Division","volume":"13","author":"Wacnik","year":"2022","journal-title":"MBio"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1128\/JB.187.5.1815-1824.2005","article-title":"Role of penicillin-binding protein 2 (PBP2) in the antibiotic susceptibility and cell wall cross-linking of Staphylococcus aureus: Evidence for the cooperative functioning of PBP2, PBP4, and PBP2A","volume":"187","author":"Tomasz","year":"2005","journal-title":"J. Bacteriol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1111\/j.1365-2958.2004.04420.x","article-title":"Recruitment of penicillin-binding protein PBP2 to the division site of Staphylococcus aureus is dependent on its transpeptidation substrates","volume":"55","author":"Pinho","year":"2004","journal-title":"Mol. Microbiol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"6525","DOI":"10.1128\/JB.183.22.6525-6531.2001","article-title":"Complementation of the Essential Peptidoglycan Transpeptidase Function of Penicillin-Binding Protein 2 (PBP2) by the Drug Resistance Protein PBP2A in Staphylococcus aureus","volume":"183","author":"Pinho","year":"2001","journal-title":"J. Bacteriol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e1338","DOI":"10.1002\/mbo3.1338","article-title":"The cell cycle of Staphylococcus aureus: An updated review","volume":"12","author":"Barbuti","year":"2023","journal-title":"Microbiologyopen"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1038\/s41564-019-0437-2","article-title":"SEDS\u2013bPBP pairs direct lateral and septal peptidoglycan synthesis in Staphylococcus aureus","volume":"4","author":"Reichmann","year":"2019","journal-title":"Nat. Microbiol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1016\/j.bpj.2014.07.029","article-title":"Reduction of the Peptidoglycan Crosslinking Causes a Decrease in Stiffness of the Staphylococcus aureus Cell Envelope","volume":"107","author":"Loskill","year":"2014","journal-title":"Biophys. J."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1128\/JB.182.4.1074-1079.2000","article-title":"Cloning, characterization, and inactivation of the gene pbpC, encoding penicillin-binding protein 3 of Staphylococcus aureus","volume":"182","author":"Pinho","year":"2000","journal-title":"J. Bacteriol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"10886","DOI":"10.1073\/pnas.191260798","article-title":"An acquired and a native penicillin-binding protein cooperate in building the cell wall of drug-resistant staphylococci","volume":"98","author":"Pinho","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e0015921","DOI":"10.1128\/mmbr.00159-21","article-title":"An Interplay of Multiple Positive and Negative Factors Governs Methicillin Resistance in Staphylococcus aureus","volume":"86","author":"Bilyk","year":"2022","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1093\/femsre\/fux007","article-title":"Antibiotic resistance in Staphylococcus aureus. Current status and future prospects","volume":"41","author":"Foster","year":"2017","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"4051","DOI":"10.1128\/AAC.00084-09","article-title":"Molecular Basis and Phenotype of Methicillin Resistance in Staphylococcus aureus and Insights into New \u03b2-Lactams That Meet the Challenge","volume":"53","author":"Llarrull","year":"2009","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1128\/JB.184.2.588-591.2002","article-title":"Direct Quantitation of the Numbers of Individual Penicillin-Binding Proteins per Cell in Staphylococcus aureus","volume":"184","author":"Pucci","year":"2002","journal-title":"J. Bacteriol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"iv17","DOI":"10.1093\/jac\/dkq252","article-title":"Ceftaroline activity against pathogens associated with complicated skin and skin structure infections: Results from an international surveillance study","volume":"65","author":"Jones","year":"2010","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1922","DOI":"10.1128\/AAC.04068-14","article-title":"Missense mutations in PBP2A affecting ceftaroline susceptibility detected in epidemic hospital-acquired Methicillin-resistant Staphylococcus aureus clonotypes ST228 and ST247 in Western Switzerland archived since 1998","volume":"59","author":"Kelley","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"e0074522","DOI":"10.1128\/aac.00745-22","article-title":"Reduced Ceftaroline Susceptibility among Invasive MRSA Infections in Children: A Clinical and Genomic Investigation","volume":"66","author":"McNeil","year":"2022","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"6668","DOI":"10.1128\/AAC.03622-14","article-title":"PBP2a Mutations Causing High-Level Ceftaroline Resistance in Clinical Methicillin-Resistant Staphylococcus aureus Isolates","volume":"58","author":"Long","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2488","DOI":"10.1093\/jac\/dkv131","article-title":"Molecular characterization of MRSA isolates bracketing the current EUCAST ceftaroline-susceptible breakpoint for Staphylococcus aureus: The role of PBP2a in the activity of ceftaroline","volume":"70","author":"Lahiri","year":"2015","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"e00485-18","DOI":"10.1128\/AAC.00485-18","article-title":"Ceftaroline Resistance by Clone-Specific Polymorphism in Penicillin-Binding Protein 2a of Methicillin-Resistant Staphylococcus aureus","volume":"62","author":"Lee","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2960","DOI":"10.1128\/AAC.05004-14","article-title":"Ceftobiprole- and ceftaroline-resistant methicillin-resistant Staphylococcus aureus","volume":"59","author":"Chan","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1128\/AAC.5.1.25","article-title":"Cefoxitin, a Semisynthetic Cephamycin Antibiotic: Susceptibility Studies","volume":"5","author":"Wallick","year":"1974","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"131","DOI":"10.7164\/antibiotics.23.131","article-title":"Cefazolin, a new semisynthetic cephalosporin antibiotic. I. Synthesis and chemical properties of cefazolin","volume":"23","author":"Kariyone","year":"1970","journal-title":"J. Antibiot."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"137","DOI":"10.7164\/antibiotics.23.137","article-title":"Cefazolin, a new semisynthetic cephalosporin antibiotic. II. In vitro and in vivo antimicrobial activity","volume":"23","author":"Nishida","year":"1970","journal-title":"J. Antibiot."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1848","DOI":"10.1128\/AAC.32.12.1848","article-title":"Mechanism of action of cephalosporins and resistance caused by decreased affinity for penicillin-binding proteins in Bacteroides fragilis","volume":"32","author":"Yotsuji","year":"1988","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2427","DOI":"10.1016\/S0968-0896(03)00126-3","article-title":"TAK-599, a novel N-Phosphono type prodrug of anti-MRSA cephalosporin T-91825: Synthesis, physicochemical and pharmacological properties","volume":"11","author":"Ishikawa","year":"2003","journal-title":"Bioorg. Med. Chem."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"19854","DOI":"10.1074\/jbc.RA118.004952","article-title":"Structural and kinetic analyses of penicillin-binding protein 4 (PBP4)-mediated antibiotic resistance in Staphylococcus aureus","volume":"293","author":"Alexander","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"e02727-16","DOI":"10.1128\/AAC.02727-16","article-title":"High-level resistance of Staphylococcus aureus to \u03b2-Lactam antibiotics mediated by penicillin-binding protein 4 (PBP4)","volume":"61","author":"Hamilton","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Greninger, A.L., Chatterjee, S.S., Chan, L.C., Hamilton, S.M., Chambers, H.F., and Chiu, C.Y. (2016). Whole-genome sequencing of methicillin-resistant Staphylococcus aureus resistant to fifth-generation cephalosporins reveals potential non-meca mechanisms of resistance. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0149541"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1093\/jac\/dkf249","article-title":"In vitro evaluation of BAL9141, a novel parenteral cephalosporin active against oxacillin-resistant staphylococci","volume":"50","author":"Jones","year":"2002","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1128\/AAC.01403-07","article-title":"In vitro selection and characterization of ceftobiprole-resistant methicillin-resistant Staphylococcus aureus","volume":"52","author":"Banerjee","year":"2008","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"e01663-18","DOI":"10.1128\/AAC.01663-18","article-title":"High Rate of Ceftobiprole Resistance among Clinical Methicillin-Resistant Staphylococcus aureus Isolates from a Hospital in Central Italy","volume":"62","author":"Morroni","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"e2106022118","DOI":"10.1073\/pnas.2106022118","article-title":"Demonstration of the role of cell wall homeostasis in Staphylococcus aureus growth and the action of bactericidal antibiotics","volume":"118","author":"Salamaga","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/j.mib.2013.06.012","article-title":"Auxiliary factors: A chink in the armor of MRSA resistance to \u03b2-lactam antibiotics","volume":"16","author":"Roemer","year":"2013","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/s00203-002-0436-0","article-title":"Factors influencing methicillin resistance in staphylococci","volume":"178","author":"Rohrer","year":"2002","journal-title":"Arch. Microbiol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"2590","DOI":"10.1128\/AAC.38.11.2590","article-title":"Reassessment of the number of auxiliary genes essential for expression of high-level methicillin resistance in Staphylococcus aureus","volume":"38","author":"Tomasz","year":"1994","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"e00313-17","DOI":"10.1128\/AAC.00313-17","article-title":"Antibiotic Resistance as a Stress Response: Recovery of High-Level Oxacillin Resistance in Methicillin-Resistant Staphylococcus aureus \u201cAuxiliary\u201d (fem) Mutants by Induction of the Stringent Stress Response","volume":"61","author":"Kim","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"e01000-13","DOI":"10.1128\/mBio.01000-13","article-title":"Novel Determinants of Antibiotic Resistance: Identification of Mutated Loci in Highly Methicillin-Resistant Subpopulations of Methicillin-Resistant Staphylococcus aureus","volume":"5","author":"Dordel","year":"2014","journal-title":"MBio"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"16907","DOI":"10.1038\/s41598-020-73796-5","article-title":"Identification and characterization of mutations responsible for the \u03b2-lactam resistance in oxacillin-susceptible mecA-positive Staphylococcus aureus","volume":"10","author":"Boonsiri","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1128\/AAC.36.7.1367","article-title":"Mapping and characterization of multiple chromosomal factors involved in methicillin resistance in Staphylococcus aureus","volume":"36","author":"Gustafson","year":"1992","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1089\/mdr.1999.5.163","article-title":"Antibiotic resistance as a stress response: Complete sequencing of a large number of chromosomal loci in Staphylococcus aureus strain COL that impact on the expression of resistance to methicillin","volume":"5","author":"Wu","year":"1999","journal-title":"Microb. Drug Resist."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.bbamcr.2011.06.007","article-title":"ClpXP, an ATP-powered unfolding and protein-degradation machine","volume":"1823","author":"Baker","year":"2012","journal-title":"Biochim. Biophys. Acta\u2013Mol. Cell Res."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Jensen, C., B\u00e6k, K.T., Gallay, C., Thals\u00f8-Madsen, I., Xu, L., Jousselin, A., Ruiz Torrubia, F., Paulander, W., Pereira, A.R., and Veening, J.-W. (2019). The ClpX chaperone controls autolytic splitting of Staphylococcus aureus daughter cells, but is bypassed by \u03b2-lactam antibiotics or inhibitors of WTA biosynthesis. PLoS Pathog., 15.","DOI":"10.1371\/journal.ppat.1008044"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"e01228-16","DOI":"10.1128\/mBio.01228-16","article-title":"The cell wall polymer lipoteichoic acid becomes nonessential in Staphylococcus aureus cells lacking the ClpX chaperone","volume":"7","author":"Baek","year":"2016","journal-title":"MBio"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1046\/j.1365-2958.2003.03524.x","article-title":"Alternative roles of ClpX and ClpP in Staphylococcus aureus stress tolerance and virulence","volume":"48","author":"Frees","year":"2003","journal-title":"Mol. Microbiol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"4593","DOI":"10.1128\/AAC.02802-14","article-title":"\u03b2-lactam resistance in methicillin-resistant Staphylococcus aureus USA300 is increased by inactivation of the ClpXP protease","volume":"58","author":"Mogensen","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Jelsbak, L., Ingmer, H., Valihrach, L., Cohn, M.T., Christiansen, M.H.G., Kallipolitis, B.H., and Frees, D. (2010). The Chaperone ClpX Stimulates Expression of Staphylococcus aureus Protein A by Rot Dependent and Independent Pathways. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0012752"},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Corrigan, R.M., Abbott, J.C., Burhenne, H., Kaever, V., and Gr\u00fcndling, A. (2011). c-di-AMP Is a New Second Messenger in Staphylococcus aureus with a Role in Controlling Cell Size and Envelope Stress. PLoS Pathog., 7.","DOI":"10.1371\/journal.ppat.1002217"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1038\/nrmicro3069","article-title":"Cyclic di-AMP: Another second messenger enters the fray","volume":"11","author":"Corrigan","year":"2013","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1128\/AAC.05148-11","article-title":"Loss of Function of the GdpP Protein Leads to Joint \u03b2-Lactam\/Glycopeptide Tolerance in Staphylococcus aureus","volume":"56","author":"Griffiths","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"e00091-18","DOI":"10.1128\/AAC.00091-18","article-title":"Genetic Diversity among Staphylococcus aureus Isolates Showing Oxacillin and\/or Cefoxitin Resistance Not Linked to the Presence of mec Genes","volume":"62","author":"Roisin","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"4900","DOI":"10.1128\/AAC.00594-10","article-title":"A mec A-Negative Strain of Methicillin-Resistant S taphylococcus aureus with High-Level \u03b2-Lactam Resistance Contains Mutations in Three Genes","volume":"54","author":"Banerjee","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"3345","DOI":"10.1128\/JCM.01354-12","article-title":"Analysis of Borderline Oxacillin-Resistant Staphylococcus aureus (BORSA) Strains Isolated in Tunisia","volume":"50","author":"Maalej","year":"2012","journal-title":"J. Clin. Microbiol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"e01431-21","DOI":"10.1128\/AAC.01431-21","article-title":"Loss of GdpP Function in Staphylococcus aureus Leads to \u03b2-Lactam Tolerance and Enhanced Evolution of \u03b2-Lactam Resistance","volume":"66","author":"Poon","year":"2022","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Panchal, V.V., Griffiths, C., Mosaei, H., Bilyk, B., Sutton, J.A.F., Carnell, O.T., Hornby, D.P., Green, J., Hobbs, J.K., and Kelley, W.L. (2020). Evolving MRSA: High-level \u03b2-lactam resistance in Staphylococcus aureus is associated with RNA Polymerase alterations and fine tuning of gene expression. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008672"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"4861","DOI":"10.1128\/AAC.00720-13","article-title":"Mutation of RNA Polymerase \u03b2-Subunit Gene Promotes Heterogeneous-to-Homogeneous Conversion of \u03b2-Lactam Resistance in Methicillin-Resistant Staphylococcus aureus","volume":"57","author":"Aiba","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.3389\/fmicb.2015.01174","article-title":"Quorum-sensing regulation in staphylococci\u2014An overview","volume":"6","author":"Le","year":"2015","journal-title":"Front. Microbiol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1111\/j.1574-6968.1996.tb08394.x","article-title":"Impact of sar and agr on methicillin resistance in Staphylococcus aureus","volume":"141","author":"Duran","year":"1996","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s13568-020-01000-y","article-title":"Increased resistance of a methicillin-resistant Staphylococcus aureus \u0394agr mutant with modified control in fatty acid metabolism","volume":"10","author":"Song","year":"2020","journal-title":"AMB Express"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"3176","DOI":"10.1128\/AAC.01119-09","article-title":"Fate of Mutation Rate Depends on agr Locus Expression during Oxacillin-Mediated Heterogeneous-Homogeneous Selection in Methicillin-Resistant Staphylococcus aureus Clinical Strains","volume":"55","author":"Plata","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"2239","DOI":"10.1128\/JB.01826-07","article-title":"SarA of Staphylococcus aureus Binds to the sarA Promoter To Regulate Gene Expression","volume":"190","author":"Cheung","year":"2008","journal-title":"J. Bacteriol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"2392","DOI":"10.1073\/pnas.0510439103","article-title":"Structural and function analyses of the global regulatory protein SarA from Staphylococcus aureus","volume":"103","author":"Liu","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"6462","DOI":"10.1073\/pnas.89.14.6462","article-title":"Regulation of exoprotein expression in Staphylococcus aureus by a locus (sar) distinct from agr","volume":"89","author":"Cheung","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"2243","DOI":"10.1128\/iai.65.6.2243-2249.1997","article-title":"Regulation of protein A synthesis by the sar and agr loci of Staphylococcus aureus","volume":"65","author":"Cheung","year":"1997","journal-title":"Infect. Immun."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1093\/infdis\/jiw386","article-title":"The Global Regulon sarA Regulates \u03b2-Lactam Antibiotic Resistance in Methicillin-Resistant Staphylococcus aureus In Vitro and in Endovascular Infections","volume":"214","author":"Li","year":"2016","journal-title":"J. Infect. Dis."},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Kim, B., Lee, H.-J., Jo, S.-H., Kim, M.-G., Lee, Y., Lee, W., Kim, W., Joo, H.-S., Kim, Y.-G., and Kim, J.-S. (2022). Study of SarA by DNA Affinity Capture Assay (DACA) Employing Three Promoters of Key Virulence and Resistance Genes in Methicillin-Resistant Staphylococcus aureus. Antibiotics, 11.","DOI":"10.3390\/antibiotics11121714"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1016\/j.apsb.2019.05.002","article-title":"Hypericin enhances \u03b2-lactam antibiotics activity by inhibiting sarA expression in methicillin-resistant Staphylococcus aureus","volume":"9","author":"Wang","year":"2019","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"13693","DOI":"10.1038\/s41598-018-32109-7","article-title":"The serine\/threonine kinase Stk and the phosphatase Stp regulate cell wall synthesis in Staphylococcus aureus","volume":"8","author":"Jarick","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1128\/IAI.01499-08","article-title":"Modulation of Cell Wall Structure and Antimicrobial Susceptibility by a Staphylococcus aureus Eukaryote-Like Serine\/Threonine Kinase and Phosphatase","volume":"77","author":"Beltramini","year":"2009","journal-title":"Infect. Immun."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"3637","DOI":"10.1128\/IAI.00296-10","article-title":"Role of PknB Kinase in Antibiotic Resistance and Virulence in Community-Acquired Methicillin-Resistant Staphylococcus aureus Strain USA300","volume":"78","author":"Tamber","year":"2010","journal-title":"Infect. Immun."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.ijmm.2009.08.016","article-title":"The impact of serine\/threonine phosphorylation in Staphylococcus aureus","volume":"300","author":"Ohlsen","year":"2010","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"4070","DOI":"10.1128\/JB.01813-08","article-title":"Characterization of a Serine\/Threonine Kinase Involved in Virulence of Staphylococcus aureus","volume":"191","author":"Dramsi","year":"2009","journal-title":"J. Bacteriol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"15461","DOI":"10.1073\/pnas.1205952109","article-title":"Protein cysteine phosphorylation of SarA\/MgrA family transcriptional regulators mediates bacterial virulence and antibiotic resistance","volume":"109","author":"Sun","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"e02222-19","DOI":"10.1128\/AAC.02222-19","article-title":"Stp1 Loss of Function Promotes \u03b2-Lactam Resistance in Staphylococcus aureus That Is Independent of Classical Genes","volume":"64","author":"Chatterjee","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1099\/mic.0.26674-0","article-title":"Role of the hprT\u2013ftsH locus in Staphylococcus aureus","volume":"150","author":"Lithgow","year":"2004","journal-title":"Microbiology"},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Yeo, W.-S., Jeong, B., Ullah, N., Shah, M., Ali, A., Kim, K., and Bae, T. (2021). FtsH Sensitizes Methicillin-Resistant Staphylococcus aureus to \u03b2-Lactam Antibiotics by Degrading YpfP, a Lipoteichoic Acid Synthesis Enzyme. Antibiotics, 10.","DOI":"10.3390\/antibiotics10101198"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1128\/jb.176.5.1460-1467.1994","article-title":"The femC locus of Staphylococcus aureus required for methicillin resistance includes the glutamine synthetase operon","volume":"176","author":"Gustafson","year":"1994","journal-title":"J. Bacteriol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1128\/AAC.45.3.815-824.2001","article-title":"Eagle-Type Methicillin Resistance: New Phenotype of High Methicillin Resistance under mec Regulator Gene Control","volume":"45","author":"Kondo","year":"2001","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1111\/j.1574-6968.2001.tb10819.x","article-title":"Cloning and sequencing of the gene, fmtC, which affects oxacillin resistance in methicillin-resistant Staphylococcus aureus","volume":"203","author":"Komatsuzawa","year":"2001","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1093\/jac\/45.4.421","article-title":"Tn551-mediated insertional inactivation of the fmtB gene encoding a cell wall-associated protein abolishes methicillin resistance in Staphylococcus aureus","volume":"45","author":"Komatsuzawa","year":"2000","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"106283","DOI":"10.1016\/j.ijantimicag.2021.106283","article-title":"The Novel Membrane-Associated Auxiliary Factors AuxA and AuxB Modulate \u03b2-lactam Resistance in MRSA by stabilizing Lipoteichoic Acids","volume":"57","author":"Mikkelsen","year":"2021","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1128\/AAC.02333-15","article-title":"The Staphylococcus aureus Chaperone PrsA Is a New Auxiliary Factor of Oxacillin Resistance Affecting Penicillin-Binding Protein 2A","volume":"60","author":"Jousselin","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/s42003-019-0667-0","article-title":"Thermosensitive PBP2a requires extracellular folding factors PrsA and HtrA1 for Staphylococcus aureus MRSA \u03b2-lactam resistance","volume":"2","author":"Roch","year":"2019","journal-title":"Commun. Biol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"3629","DOI":"10.1128\/AAC.06264-11","article-title":"The Posttranslocational Chaperone Lipoprotein PrsA Is Involved in both Glycopeptide and Oxacillin Resistance in Staphylococcus aureus","volume":"56","author":"Jousselin","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1128\/JB.00822-09","article-title":"Molecular basis for the role of Staphylococcus aureus penicillin binding protein 4 in antimicrobial resistance","volume":"192","author":"Navratna","year":"2010","journal-title":"J. Bacteriol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"3955","DOI":"10.1128\/AAC.00049-08","article-title":"Staphylococcus aureus PBP4 Is Essential for \u03b2-Lactam Resistance in Community-Acquired Methicillin-Resistant Strains","volume":"52","author":"Memmi","year":"2008","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"e00932-17","DOI":"10.1128\/AAC.00932-17","article-title":"PBP4 Mediates \u03b2-Lactam Resistance by Altered Function","volume":"61","author":"Chatterjee","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"801","DOI":"10.2217\/fmb-2019-0348","article-title":"Cell division protein FtsZ: From structure and mechanism to antibiotic target","volume":"15","author":"Silber","year":"2020","journal-title":"Future Microbiol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1016\/j.chembiol.2011.08.015","article-title":"Antagonism of Chemical Genetic Interaction Networks Resensitize MRSA to \u03b2-Lactam Antibiotics","volume":"18","author":"Lee","year":"2011","journal-title":"Chem. Biol."},{"key":"ref_162","first-page":"204","article-title":"Impact of FtsZ Inhibition on the Localization of the Penicillin Binding Proteins in Methicillin-Resistant Staphylococcus aureus","volume":"203","author":"Huh","year":"2021","journal-title":"J. Bacteriol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1128\/MMBR.67.4.686-723.2003","article-title":"A Continuum of Anionic Charge: Structures and Functions of D-Alanyl Teichoic Acids in Gram-Positive Bacteria","volume":"67","author":"Neuhaus","year":"2003","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"2778","DOI":"10.1093\/jac\/dkab287","article-title":"Inhibition of D-alanylation of teichoic acids overcomes resistance of methicillin-resistant Staphylococcus aureus","volume":"76","author":"Coupri","year":"2021","journal-title":"J. Antimicrob. Chemother."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/12\/9\/1362\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:38:24Z","timestamp":1760128704000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/12\/9\/1362"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,24]]},"references-count":164,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["antibiotics12091362"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics12091362","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,24]]}}}