{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:42:35Z","timestamp":1791333755637,"version":"4.3.1"},"reference-count":65,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T00:00:00Z","timestamp":1644969600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005321","name":"American College of Clinical Pharmacy","doi-asserted-by":"publisher","award":["183736"],"award-info":[{"award-number":["183736"]}],"id":[{"id":"10.13039\/100005321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["5T32AI141349"],"award-info":[{"award-number":["5T32AI141349"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Society of Infectious Diseases Pharmacists","award":["175743"],"award-info":[{"award-number":["175743"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Antimicrobial resistance to treatments for Clostridioides difficile infection (CDI) poses a significant threat to global health. C. difficile is widely thought to be susceptible to oral vancomycin, which is increasingly the mainstay of CDI treatment. However, clinical labs do not conduct C. difficile susceptibility testing, presenting a challenge to detecting the emergence and impact of resistance. In this systematic review, we describe gene determinants and associated clinical and laboratory mechanisms of vancomycin resistance in C. difficile, including drug-binding site alterations, efflux pumps, RNA polymerase mutations, and biofilm formation. Additional research is needed to further characterize these mechanisms and understand their clinical impact.<\/jats:p>","DOI":"10.3390\/antibiotics11020258","type":"journal-article","created":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T20:26:41Z","timestamp":1645043201000},"page":"258","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Genetic Mechanisms of Vancomycin Resistance in Clostridioides difficile: A Systematic Review"],"prefix":"10.3390","volume":"11","author":[{"given":"Taryn A.","family":"Eubank","sequence":"first","affiliation":[{"name":"Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, TX 77204, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne J.","family":"Gonzales-Luna","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, TX 77204, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian G.","family":"Hurdle","sequence":"additional","affiliation":[{"name":"Center of Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, TX A&M Health Science Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2063-7503","authenticated-orcid":false,"given":"Kevin W.","family":"Garey","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, TX 77204, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1732","DOI":"10.1056\/NEJMoa1801550","article-title":"Changes in Prevalence of Health Care-Associated Infections in U.S. Hospitals","volume":"379","author":"Magill","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_2","unstructured":"(2022, January 13). Antibiotic Resistance Threats in the United States, Available online: https;\/\/www.cdc.gov\/drugresistance\/pdf\/threats-report\/2019-ar-threats-report-508.pdf."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Gonzales, M., Pepin, J., Frost, E.H., Carrier, J.C., Sirard, S., Fortier, L.C., and Valiquette, L. (2010). Faecal pharmacokinetics of orally administered vancomycin in patients with suspected Clostridium difficile infection. BMC Infect. Dis., 10.","DOI":"10.1186\/1471-2334-10-363"},{"key":"ref_4","unstructured":"European Committee on Antimicrobial Susceptibility Testing (2022, January 05). Breakpoint Tables for Interpretation of MICs and Zone Diameters. Version 12.0. Available online: https:\/\/www.eucast.org\/clinical_breakpoints\/."},{"key":"ref_5","unstructured":"(2022, January 13). CLSI M100-ED31: 2021 Performance Standards for Antimicrobial Susceptibility Testing, 31st Edition. Available online: http:\/\/em100.edaptivedocs.net\/GetDoc.aspx?doc=CLSI%20M100%20ED31:2021&scope=user."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"ofab365","DOI":"10.1093\/ofid\/ofab365","article-title":"Reduced Susceptibility to Metronidazole Is Associated With Initial Clinical Failure in Clostridioides difficile Infection","volume":"8","author":"Olaitan","year":"2021","journal-title":"Open Forum Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1093\/cid\/ciu313","article-title":"Vancomycin, Metronidazole, or Tolevamer for Clostridium difficile Infection: Results From Two Multinational, Randomized, Controlled Trials","volume":"59","author":"Johnson","year":"2014","journal-title":"Clin. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1093\/cid\/ciy149","article-title":"Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA)","volume":"66","author":"McDonald","year":"2018","journal-title":"Clin. Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1944","DOI":"10.1093\/cid\/ciaa484","article-title":"Impact of Revised Infectious Diseases Society of America and Society for Healthcare Epidemiology of America Clinical Practice Guidelines on the Treatment of Clostridium difficile Infections in the United States","volume":"72","author":"Clancy","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1056\/NEJMoa0910812","article-title":"Fidaxomicin versus vancomycin for Clostridium difficile infection","volume":"364","author":"Louie","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/S1473-3099(11)70374-7","article-title":"Fidaxomicin versus vancomycin for infection with Clostridium difficile in Europe, Canada, and the USA: A double-blind, non-inferiority, randomised controlled trial","volume":"12","author":"Cornely","year":"2012","journal-title":"Lancet Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1016\/j.jiac.2018.05.010","article-title":"Efficacy and safety of fidaxomicin for the treatment of Clostridioides (Clostridium) difficile infection in a randomized, double-blind, comparative Phase III study in Japan","volume":"24","author":"Mikamo","year":"2018","journal-title":"J. Infect. Chemother."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/S1473-3099(17)30751-X","article-title":"Extended-pulsed fidaxomicin versus vancomycin for Clostridium difficile infection in patients 60 years and older (EXTEND): A randomised, controlled, open-label, phase 3b\/4 trial","volume":"18","author":"Guery","year":"2018","journal-title":"Lancet Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1093\/cid\/ciab718","article-title":"Clinical Practice Guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 Focused Update Guidelines on Management of Clostridioides difficile Infection in Adults","volume":"73","author":"Johnson","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1093\/clinids\/22.5.813","article-title":"Comparison of vancomycin, teicoplanin, metronidazole, and fusidic acid for the treatment of Clostridium difficile-associated diarrhea","volume":"22","author":"Wenisch","year":"1996","journal-title":"Clin. Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1086\/519265","article-title":"A Comparison of Vancomycin and Metronidazole for the Treatment of Clostridium difficile-Associated Diarrhea, Stratified by Disease Severity","volume":"45","author":"Zar","year":"2007","journal-title":"Clin. Infect. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1086\/506349","article-title":"Tolevamer, a novel nonantibiotic polymer, compared with vancomycin in the treatment of mild to moderately severe Clostridium difficile-associated diarrhea","volume":"43","author":"Louie","year":"2006","journal-title":"Clin. Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1001\/archinte.1986.00360180083015","article-title":"Oral bacitracin vs vancomycin therapy for Clostridium difficile-induced diarrhea. A randomized double-blind trial","volume":"146","author":"Dudley","year":"1986","journal-title":"Arch. Intern. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"102385","DOI":"10.1016\/j.anaerobe.2021.102385","article-title":"Antimicrobial resistance progression in the United Kingdom: A temporal comparison of Clostridioides difficile antimicrobial susceptibilities","volume":"70","author":"Jon","year":"2021","journal-title":"Anaerobe"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.diagmicrobio.2015.05.015","article-title":"A national survey of the molecular epidemiology of Clostridium difficile in Israel: The dissemination of the ribotype 027 strain with reduced susceptibility to vancomycin and metronidazole","volume":"83","author":"Adler","year":"2015","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.3389\/fmicb.2018.01420","article-title":"Detection and Investigation of Eagle Effect Resistance to Vancomycin in Clostridium difficile With an ATP-Bioluminescence Assay","volume":"9","author":"Jarrad","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e02054-16","DOI":"10.1128\/AAC.02054-16","article-title":"A Clostridium difficile Lineage Endemic to Costa Rican Hospitals Is Multidrug Resistant by Acquisition of Chromosomal Mutations and Novel Mobile Genetic Elements","volume":"61","author":"Murillo","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1093\/jac\/dkz513","article-title":"Constitutive expression of the cryptic vanGCd operon promotes vancomycin resistance in Clostridioides difficile clinical isolates","volume":"75","author":"Shen","year":"2020","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.jgar.2020.01.007","article-title":"Genetic relatedness, Virulence factors and Antimicrobial Resistance of C. difficile strains from hospitalized patients in a multicentric study in Brazil","volume":"22","author":"Saldanha","year":"2020","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1093\/jac\/dkt302","article-title":"In vitro selection, via serial passage, of Clostridium difficile mutants with reduced susceptibility to fidaxomicin or vancomycin","volume":"69","author":"Leeds","year":"2014","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1053\/j.gastro.2020.10.046","article-title":"Plasmid Acquisition Alters Vancomycin Susceptibility in Clostridioides difficile","volume":"160","author":"Pu","year":"2021","journal-title":"Gastroenterology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"9982","DOI":"10.1038\/s41598-017-10155-x","article-title":"CD2068 potentially mediates multidrug efflux in Clostridium difficile","volume":"7","author":"Ngernsombat","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1128\/JB.01980-12","article-title":"Multiple factors modulate biofilm formation by the anaerobic pathogen Clostridium difficile","volume":"195","author":"Leuzzi","year":"2013","journal-title":"J. Bacteriol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Tijerina-Rodriguez, L., Villarreal-Trevino, L., Baines, S.D., Morfin-Otero, R., Camacho-Ortiz, A., Flores-Trevino, S., Maldonado-Garza, H., Rodriguez-Noriega, E., and Garza-Gonzalez, E. (2019). High sporulation and overexpression of virulence factors in biofilms and reduced susceptibility to vancomycin and linezolid in recurrent Clostridium [Clostridioides] difficile infection isolates. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0220671"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Depardieu, F., Mejean, V., and Courvalin, P. (2015). Competition between VanU(G) repressor and VanR(G) activator leads to rheostatic control of vanG vancomycin resistance operon expression. PLoS Genet., 11.","DOI":"10.1371\/journal.pgen.1005170"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2459","DOI":"10.1007\/s10096-021-04311-5","article-title":"Antimicrobial resistance in Clostridioides difficile","volume":"40","author":"Knight","year":"2021","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.anaerobe.2018.06.013","article-title":"Examination of the Clostridioides (Clostridium) difficile VanZ ortholog, CD1240","volume":"53","author":"Woods","year":"2018","journal-title":"Anaerobe"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e00177-16","DOI":"10.1128\/mSphere.00177-16","article-title":"A Phenotypically Silent vanB2 Operon Carried on a Tn1549-Like Element in Clostridium difficile","volume":"1","author":"Knight","year":"2016","journal-title":"mSphere"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e00252-28","DOI":"10.1128\/mSystems.00252-18","article-title":"Independent Microevolution Mediated by Mobile Genetic Elements of Individual Clostridium difficile Isolates from Clade 4 Revealed by Whole-Genome Sequencing","volume":"4","author":"Wu","year":"2019","journal-title":"mSystems"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1111\/mmi.12299","article-title":"The functional vanGCd cluster of Clostridium difficile does not confer vancomycin resistance","volume":"89","author":"Ammam","year":"2013","journal-title":"Mol. Microbiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"22135","DOI":"10.1038\/s41598-020-79123-2","article-title":"Phylogenomic analysis of Clostridioides difficile ribotype 106 strains reveals novel genetic islands and emergent phenotypes","volume":"10","author":"Roxas","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s13099-017-0191-z","article-title":"Genome characterization of a novel binary toxin-positive strain of Clostridium difficile and comparison with the epidemic 027 and 078 strains","volume":"9","author":"Peng","year":"2017","journal-title":"Gut Pathog."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1139\/w2012-002","article-title":"Distribution of the vanG-like gene cluster in Clostridium difficile clinical isolates","volume":"58","author":"Ammam","year":"2012","journal-title":"Can. J. Microbiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1128\/JB.00680-09","article-title":"Analysis of the mobilization functions of the vancomycin resistance transposon Tn1549, a member of a new family of conjugative elements","volume":"192","author":"Tsvetkova","year":"2010","journal-title":"J. Bacteriol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"201","DOI":"10.2174\/1568005014606116","article-title":"E. coli MurG: A paradigm for a superfamily of glycosyltransferases","volume":"1","author":"Ha","year":"2001","journal-title":"Curr. Drug Targets Infect. Disord."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/978-981-13-7647-4_2","article-title":"ABC Family Transporters","volume":"1141","author":"Liu","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1007\/s00203-008-0385-3","article-title":"Detection and characterization of an ABC transporter in Clostridium hathewayi","volume":"190","author":"Rafii","year":"2008","journal-title":"Arch. Microbiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.anaerobe.2009.01.008","article-title":"Characterization of an ATP-binding cassette from Clostridium perfringens with homology to an ABC transporter from Clostridium hathewayi","volume":"15","author":"Rafii","year":"2009","journal-title":"Anaerobe"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1099\/mic.0.045997-0","article-title":"The dlt operon confers resistance to cationic antimicrobial peptides in Clostridium difficile","volume":"157","author":"McBride","year":"2011","journal-title":"Microbiology (Reading)"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1099\/jmm.0.000427","article-title":"Manual curation and reannotation of the genomes of Clostridium difficile 630Deltaerm and C. difficile 630","volume":"66","author":"Dannheim","year":"2017","journal-title":"J. Med. Microbiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1086\/596315","article-title":"High frequency of rifampin resistance identified in an epidemic Clostridium difficile clone from a large teaching hospital","volume":"48","author":"Curry","year":"2009","journal-title":"Clin. Infect. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1099\/jmm.0.029470-0","article-title":"Killing kinetics of fidaxomicin and its major metabolite, OP-1118, against Clostridium difficile","volume":"60","author":"Babakhani","year":"2011","journal-title":"J. Med. Microbiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"102387","DOI":"10.1016\/j.anaerobe.2021.102387","article-title":"Systems biology evaluation of refractory Clostridioides difficile infection including multiple failures of fecal microbiota transplantation","volume":"70","author":"Spinler","year":"2021","journal-title":"Anaerobe"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1128\/AAC.00039-06","article-title":"Genetic changes that correlate with reduced susceptibility to daptomycin in Staphylococcus aureus","volume":"50","author":"Friedman","year":"2006","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2680","DOI":"10.1128\/JCM.02144-10","article-title":"Impact of rpoB mutations on reduced vancomycin susceptibility in Staphylococcus aureus","volume":"49","author":"Watanabe","year":"2011","journal-title":"J. Clin. Microbiol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Meza-Torres, J., Auria, E., Dupuy, B., and Tremblay, Y.D.N. (2021). Wolf in Sheep\u2019s Clothing: Clostridioides difficile Biofilm as a Reservoir for Recurrent Infections. Microorganisms, 9.","DOI":"10.3390\/microorganisms9091922"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1078\/1438-4221-00196","article-title":"Mechanisms of antibiotic resistance in bacterial biofilms","volume":"292","author":"Stewart","year":"2002","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1093\/jac\/dks493","article-title":"The membrane as a target for controlling hypervirulent Clostridium difficile infections","volume":"68","author":"Wu","year":"2013","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1111\/j.1574-695X.2012.00962.x","article-title":"Biofilm-growing intestinal anaerobic bacteria","volume":"65","author":"Donelli","year":"2012","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Semenyuk, E.G., Laning, M.L., Foley, J., Johnston, P.F., Knight, K.L., Gerding, D.N., and Driks, A. (2014). Spore formation and toxin production in Clostridium difficile biofilms. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0087757"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"7174","DOI":"10.1128\/JB.00578-07","article-title":"Cwp84, a surface-associated protein of Clostridium difficile, is a cysteine protease with degrading activity on extracellular matrix proteins","volume":"189","author":"Janoir","year":"2007","journal-title":"J. Bacteriol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"34666","DOI":"10.1074\/jbc.M109.051177","article-title":"Cwp84, a surface-associated cysteine protease, plays a role in the maturation of the surface layer of Clostridium difficile","volume":"284","author":"Kirby","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2331","DOI":"10.1111\/j.1462-2920.2008.01658.x","article-title":"Roles of type IV pili, flagellum-mediated motility and extracellular DNA in the formation of mature multicellular structures in Pseudomonas aeruginosa biofilms","volume":"10","author":"Barken","year":"2008","journal-title":"Environ. Microbiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1046\/j.1365-2958.2001.02709.x","article-title":"The sporulation transcription factor Spo0A is required for biofilm development in Bacillus subtilis","volume":"42","author":"Hamon","year":"2001","journal-title":"Mol. Microbiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/nrmicro2960","article-title":"Sticking together: Building a biofilm the Bacillus subtilis way","volume":"11","author":"Vlamakis","year":"2013","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Zhao, X., Yu, Z., and Ding, T. (2020). Quorum-Sensing Regulation of Antimicrobial Resistance in Bacteria. Microorganisms, 8.","DOI":"10.3390\/microorganisms8030425"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"9903","DOI":"10.1038\/s41598-019-46143-6","article-title":"Clostridioides difficile LuxS mediates inter-bacterial interactions within biofilms","volume":"9","author":"Slater","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1038\/nrmicro1916","article-title":"Establishing bacterial communities by \u2018word of mouth\u2019: LuxS and autoinducer 2 in biofilm development","volume":"6","author":"Hardie","year":"2008","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1046\/j.1365-2958.1997.4251782.x","article-title":"Quorum sensing by peptide pheromones and two-component signal-transduction systems in Gram-positive bacteria","volume":"24","author":"Kleerebezem","year":"1997","journal-title":"Mol. Microbiol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Buehrle, D., and Clancy, C.J. (2021). Medicare Prescription Plans Limit Access to Recommended Drugs for Clostridioides difficile Infection. Clin. Infect. Dis., ciab898.","DOI":"10.1093\/cid\/ciab898"}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/11\/2\/258\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:21:06Z","timestamp":1760134866000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/11\/2\/258"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,16]]},"references-count":65,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["antibiotics11020258"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics11020258","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,16]]}}}