{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T12:02:26Z","timestamp":1789041746516,"version":"build-2803163510"},"reference-count":65,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T00:00:00Z","timestamp":1678320000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100021772","name":"Deanship of Scientific Research, University of Jordan","doi-asserted-by":"publisher","award":["2073"],"award-info":[{"award-number":["2073"]}],"id":[{"id":"10.13039\/501100021772","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021772","name":"Deanship of Scientific Research, University of Jordan","doi-asserted-by":"publisher","award":["2460"],"award-info":[{"award-number":["2460"]}],"id":[{"id":"10.13039\/501100021772","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Hamdi mango centre for scientific research","award":["2017"],"award-info":[{"award-number":["2017"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Minimizing antibiotic resistance is a key motivation strategy in designing and developing new and combination therapy. In this study, a combination of the antibiotics (cefixime, levofloxacin and gentamicin) with <jats:italic>Lysobacter enzymogenes<\/jats:italic> (<jats:italic>L<\/jats:italic>. <jats:italic>enzymogenes<\/jats:italic>) bioactive proteases present in the cell- free supernatant (CFS) have been investigated against the Gram-positive methicillin-sensitive <jats:italic>Staphylococcus aureus<\/jats:italic> (MSSA), methicillin-resistant <jats:italic>Staphylococcus aureus<\/jats:italic> (MRSA) and the Gram-negative <jats:italic>Escherichia coli<\/jats:italic> (<jats:italic>E<\/jats:italic>. <jats:italic>coli<\/jats:italic> O157:H7). Results indicated that <jats:italic>L<\/jats:italic>. <jats:italic>enzymogenes<\/jats:italic> CFS had maximum proteolytic activity after 11 days of incubation and higher growth inhibitory properties against MSSA and MRSA compared to <jats:italic>E<\/jats:italic>. <jats:italic>coli<\/jats:italic> (O157:H7). The combination of <jats:italic>L<\/jats:italic>. <jats:italic>enzymogenes<\/jats:italic> CFS with cefixime, gentamicin and levofloxacin at sub-MIC levels, has potentiated their bacterial inhibition capacity. Interestingly, combining cefixime with <jats:italic>L<\/jats:italic>. <jats:italic>enzymogenes<\/jats:italic> CFS restored its antibacterial activity against MRSA. The MTT assay revealed that <jats:italic>L<\/jats:italic>. <jats:italic>enzymogenes<\/jats:italic> CFS has no significant reduction in human normal skin fibroblast (CCD-1064SK) cell viability. In conclusion, <jats:italic>L<\/jats:italic>. <jats:italic>enzymogenes<\/jats:italic> bioactive proteases are natural potentiators for antimicrobials with different bacterial targets including cefixime, gentamicin and levofloxacin representing the beginning of a modern and efficient era in the battle against multidrug-resistant pathogens.<\/jats:p>","DOI":"10.1371\/journal.pone.0282705","type":"journal-article","created":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T18:43:40Z","timestamp":1678387420000},"page":"e0282705","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Antibiotic\u2014Lysobacter enzymogenes proteases combination as a novel virulence attenuating therapy"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5554-0926","authenticated-orcid":true,"given":"Ghadeer A. R. 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Bollenbach","year":"2015","journal-title":"Current opinion in microbiology"},{"key":"pone.0282705.ref022","doi-asserted-by":"crossref","first-page":"112513","DOI":"10.1016\/j.ejmech.2020.112513","article-title":"Design, synthesis and antimicrobial evaluation of novel glycosylated-fluoroquinolones derivatives","volume":"202","author":"AAM Mohammed","year":"2020","journal-title":"European Journal of Medicinal Chemistry"},{"issue":"14","key":"pone.0282705.ref023","doi-asserted-by":"crossref","first-page":"3005","DOI":"10.1016\/j.bmc.2019.05.038","article-title":"Fluoroquinolones structural and medicinal developments (2013\u20132018): Where are we now?","volume":"27","author":"GA Suaifan","year":"2019","journal-title":"Bioorganic & medicinal chemistry"},{"key":"pone.0282705.ref024","doi-asserted-by":"crossref","first-page":"684109","DOI":"10.1155\/2015\/684109","article-title":"Bioactive Natural Products: Facts, Applications, and Challenges","volume":"2015","author":"Y Kourkoutas","year":"2015","journal-title":"BioMed Research International"},{"issue":"1","key":"pone.0282705.ref025","doi-asserted-by":"crossref","first-page":"27","DOI":"10.3390\/antibiotics9010027","article-title":"Essential oil of Croton ceanothifolius Baill. potentiates the effect of antibiotics against multiresistant bacteria","volume":"9","author":"ACJ. de Ara\u00fajo","year":"2020","journal-title":"Antibiotics"},{"issue":"2","key":"pone.0282705.ref026","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1093\/clinids\/4.2.282","article-title":"Antibiotic synergism and antimicrobial combinations in clinical infections george","volume":"4","author":"GM Eliopoulos","year":"1982","journal-title":"Reviews of infectious diseases"},{"issue":"19","key":"pone.0282705.ref027","doi-asserted-by":"crossref","first-page":"12415","DOI":"10.1021\/acs.chemrev.7b00283","article-title":"Natural products as platforms to overcome antibiotic resistance","volume":"117","author":"SE Rossiter","year":"2017","journal-title":"Chemical reviews"},{"key":"pone.0282705.ref028","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/978-3-319-52669-0_10","article-title":"Bioactive natural products: an overview, with particular emphasis on those possessing potential to inhibit microbial quorum sensing","volume":"2","author":"V Kothari","year":"2017","journal-title":"Microbial Applications"},{"key":"pone.0282705.ref029","doi-asserted-by":"crossref","first-page":"29","DOI":"10.4103\/0973-7847.156329","article-title":"Antibiotics and bioactive natural products in treatment of methicillin resistant Staphylococcus aureus: A brief review","volume":"9","author":"A Kali","year":"2015","journal-title":"Pharmacognosy Reviews"},{"key":"pone.0282705.ref030","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/7355_2017_23","article-title":"Synergistic antibiotic combinations","author":"K. Bush","year":"2017","journal-title":"Antibacterials"},{"issue":"1","key":"pone.0282705.ref031","doi-asserted-by":"crossref","first-page":"111","DOI":"10.3349\/ymj.2010.51.1.111","article-title":"In-vitro efficacy of synergistic antibiotic combinations in multidrug resistant Pseudomonas aeruginosa strains","volume":"51","author":"D Dundar","year":"2010","journal-title":"Yonsei medical journal"},{"key":"pone.0282705.ref032","doi-asserted-by":"crossref","first-page":"747760","DOI":"10.3389\/fmicb.2021.747760","article-title":"Boosting synergistic effects of short antimicrobial peptides with conventional antibiotics against resistant bacteria","volume":"12","author":"C-L Wu","year":"2021","journal-title":"Frontiers in Microbiology"},{"issue":"3","key":"pone.0282705.ref033","doi-asserted-by":"crossref","first-page":"185","DOI":"10.3390\/ph14030185","article-title":"Evaluation of the synergistic antibacterial effects of fosfomycin in combination with selected antibiotics against carbapenem\u2013resistant Acinetobacter baumannii","volume":"14","author":"OF Nwabor","year":"2021","journal-title":"Pharmaceuticals"},{"key":"pone.0282705.ref034","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1016\/j.bios.2016.10.023","article-title":"Paper-based magnetic nanoparticle-peptide probe for rapid and quantitative colorimetric detection of Escherichia coli O157:H7","volume":"92","author":"GARY Suaifan","year":"2017","journal-title":"Biosensors and Bioelectronics"},{"key":"pone.0282705.ref035","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.bios.2016.11.047","article-title":"Rapid and low-cost biosensor for the detection of Staphylococcus aureus","volume":"90","author":"GA Suaifan","year":"2017","journal-title":"Biosensors and Bioelectronics"},{"key":"pone.0282705.ref036","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.talanta.2019.01.067","article-title":"Engineered colorimetric detection of Staphylococcus aureus extracellular proteases","volume":"198","author":"GA Suaifan","year":"2019","journal-title":"Talanta"},{"key":"pone.0282705.ref037","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1016\/j.bios.2016.07.043","article-title":"Rapid colorimetric sensing platform for the detection of Listeria monocytogenes foodborne pathogen","volume":"86","author":"S Alhogail","year":"2016","journal-title":"Biosensors and Bioelectronics"},{"issue":"26","key":"pone.0282705.ref038","doi-asserted-by":"crossref","first-page":"21684","DOI":"10.1021\/acsomega.9b02080","article-title":"Rapid colorimetric detection of Pseudomonas aeruginosa in clinical isolates using a magnetic nanoparticle biosensor","volume":"4","author":"S Alhogail","year":"2019","journal-title":"ACS omega"},{"key":"pone.0282705.ref039","doi-asserted-by":"crossref","first-page":"112910","DOI":"10.1016\/j.bios.2020.112910","article-title":"Aptasensor for the detection of Methicillin resistant Staphylococcus aureus on contaminated surfaces","volume":"176","author":"MA Raji","year":"2021","journal-title":"Biosensors and Bioelectronics"},{"issue":"23","key":"pone.0282705.ref040","doi-asserted-by":"crossref","first-page":"5614","DOI":"10.1039\/c2an36243k","article-title":"Wash-less and highly sensitive assay for prostate specific antigen detection","volume":"137","author":"GA Suaifan","year":"2012","journal-title":"Analyst"},{"issue":"7","key":"pone.0282705.ref041","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1111\/1469-0691.12691","article-title":"New epidemiology of Staphylococcus aureus infections in the Middle East","volume":"20","author":"S. Tokajian","year":"2014","journal-title":"Clinical Microbiology and Infection"},{"issue":"1","key":"pone.0282705.ref042","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.cll.2009.11.001","article-title":"Shiga toxin\u2013producing Escherichia coli (STEC)","volume":"30","author":"JM Hunt","year":"2010","journal-title":"Clinics in laboratory medicine"},{"issue":"4","key":"pone.0282705.ref043","doi-asserted-by":"crossref","first-page":"603","DOI":"10.3201\/eid1104.040739","article-title":"Epidemiology of Escherichia coli O157: H7 outbreaks, united states, 1982\u20132002","volume":"11","author":"JM Rangel","year":"2005","journal-title":"Emerging infectious diseases"},{"key":"pone.0282705.ref044","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.3389\/fmicb.2015.01243","article-title":"Diversity and activity of Lysobacter species from disease suppressive soils","volume":"6","author":"R G\u00f3mez Exp\u00f3sito","year":"2015","journal-title":"Frontiers in microbiology"},{"issue":"19","key":"pone.0282705.ref045","doi-asserted-by":"crossref","DOI":"10.3791\/899-v","article-title":"Sigma\u2019s non-specific protease activity assay-casein as a substrate","author":"C. Cupp-Enyard","year":"2008","journal-title":"Journal of visualized experiments: JoVE"},{"key":"pone.0282705.ref046","unstructured":"Wikler MA. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically: approved standard. CLSI (NCCLS). 2006;26:M7-A."},{"issue":"2","key":"pone.0282705.ref047","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.3390\/biom5021178","article-title":"A microplate growth inhibition assay for screening bacteriocins against Listeria monocytogenes to differentiate their mode-of-action","volume":"5","author":"PP Vijayakumar","year":"2015","journal-title":"Biomolecules"},{"issue":"6","key":"pone.0282705.ref048","article-title":"Analysis of cell viability by the alamarblue assay","volume":"2018","author":"P Kumar","year":"2018","journal-title":"Cold Spring Harbor Protocols"},{"issue":"6","key":"pone.0282705.ref049","doi-asserted-by":"crossref","first-page":"921","DOI":"10.4314\/tjpr.v13i6.14","article-title":"Cytotoxicity screening of plants of genus Piper in breast cancer cell lines","volume":"13","author":"S Sriwiriyajan","year":"2014","journal-title":"Tropical Journal of Pharmaceutical Research"},{"issue":"4","key":"pone.0282705.ref050","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1016\/j.tiv.2012.02.006","article-title":"Exocytosis of MTT formazan could exacerbate cell injury","volume":"26","author":"L L\u00fc","year":"2012","journal-title":"Toxicology in vitro"},{"issue":"18","key":"pone.0282705.ref051","doi-asserted-by":"crossref","first-page":"4221","DOI":"10.1016\/j.bmcl.2017.08.027","article-title":"Antibiotic adjuvants\u2014A strategy to unlock bacterial resistance to antibiotics","volume":"27","author":"C. Gonz\u00e1lez-Bello","year":"2017","journal-title":"Bioorganic & Medicinal Chemistry Letters"},{"issue":"2","key":"pone.0282705.ref052","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1021\/acsanm.0c03029","article-title":"Chrysophanol-Functionalized Silver Nanoparticles for Anti-Adhesive and Anti-Biofouling Coatings to Prevent Urinary Catheter-Associated Infections","volume":"4","author":"P Prateeksha","year":"2021","journal-title":"ACS Applied Nano Materials"},{"issue":"58","key":"pone.0282705.ref053","doi-asserted-by":"crossref","first-page":"36459","DOI":"10.1039\/D1RA06238G","article-title":"Bacterial virulence factors: a target for heterocyclic compounds to combat bacterial resistance","volume":"11","author":"RH Abd El-Aleam","year":"2021","journal-title":"RSC Adv"},{"issue":"5","key":"pone.0282705.ref054","doi-asserted-by":"crossref","first-page":"886","DOI":"10.3390\/molecules24050886","article-title":"In-vitro evaluation of different antimicrobial combinations with and without colistin against carbapenem-resistant Acinetobacter baumannii","volume":"24","author":"A Oliva","year":"2019","journal-title":"Molecules"},{"issue":"1","key":"pone.0282705.ref055","first-page":"1","article-title":"Outer-membrane-acting peptides and lipid II-targeting antibiotics cooperatively kill Gram-negative pathogens","volume":"4","author":"Q Li","year":"2021","journal-title":"Communications biology"},{"key":"pone.0282705.ref056","first-page":"2019","article-title":"Difference between Gram positive and Gram negative bacteria","volume":"29","author":"G. Karki","year":"2018","journal-title":"Online biology notes Accessed March"},{"issue":"1","key":"pone.0282705.ref057","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.bbamem.2014.05.031","article-title":"Peptidoglycan architecture of Gram-positive bacteria by solid-state NMR","volume":"1848","author":"SJ Kim","year":"2015","journal-title":"Biochimica et Biophysica Acta (BBA)-Biomembranes"},{"issue":"7","key":"pone.0282705.ref058","doi-asserted-by":"crossref","first-page":"790","DOI":"10.7164\/antibiotics.37.790","article-title":"Mechanism of action of the new orally active cephalosporin FK027","volume":"37","author":"Y SHIGI","year":"1984","journal-title":"The Journal of antibiotics"},{"issue":"4","key":"pone.0282705.ref059","doi-asserted-by":"crossref","first-page":"677","DOI":"10.2165\/00003495-199447040-00008","article-title":"Levofloxacin","volume":"47","author":"R Davis","year":"1994","journal-title":"Drugs"},{"issue":"11","key":"pone.0282705.ref060","first-page":"817","article-title":"Gentamicin sulfate, new antibiotic against Gram-negative bacilli: Laboratory, pharmacological, and clinical evaluation","volume":"189","author":"RL Jao","year":"1964","journal-title":"Jama"},{"issue":"11","key":"pone.0282705.ref061","first-page":"728","article-title":"Current pattern of antibiotic resistance in Staphylococcus aureus clinical isolates and the emergence of vancomycin resistance","volume":"20","author":"Y Taj","year":"2010","journal-title":"J Coll Physicians Surg Pak"},{"issue":"16","key":"pone.0282705.ref062","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.4155\/fmc-2019-0167","article-title":"Antimicrobial peptides with protease stability: progress and perspective","volume":"11","author":"C Shao","year":"2019","journal-title":"Future Medicinal Chemistry"},{"issue":"1\u20132","key":"pone.0282705.ref063","first-page":"9","article-title":"An evaluation of the colorimetric assays based on enzymatic reactions used in the measurement of human natural cytotoxicity","volume":"251","author":"Q-x Niu","year":"2001","journal-title":"Journal of immunological methods"},{"issue":"5\u20136","key":"pone.0282705.ref064","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/0109-5641(95)80029-8","article-title":"Comparison of tetrazolium colorimetric and 51Cr release assays for cytotoxicity determination of dental biomaterials","volume":"11","author":"TA Bean","year":"1995","journal-title":"Dental Materials"},{"key":"pone.0282705.ref065","unstructured":"10993\u20135 I. Biological evaluation of medical devices, Part 5, Tests for Cytotoxicity: In Vitro Methods. International Organization for Standardization Geneva, Switzerland; 2009."}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0282705","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T18:44:37Z","timestamp":1678387477000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0282705"}},"subtitle":[],"editor":[{"given":"Brahma Nand","family":"Singh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,3,9]]},"references-count":65,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,3,9]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0282705","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,9]]}}}