{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T17:03:01Z","timestamp":1781715781099,"version":"3.54.5"},"reference-count":48,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T00:00:00Z","timestamp":1720483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo","award":["1171397"],"award-info":[{"award-number":["1171397"]}]},{"name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo","award":["DI-02-24\/REG"],"award-info":[{"award-number":["DI-02-24\/REG"]}]},{"name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo","award":["NCN17_093"],"award-info":[{"award-number":["NCN17_093"]}]},{"name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo","award":["1220584"],"award-info":[{"award-number":["1220584"]}]},{"name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo","award":["1221610"],"award-info":[{"award-number":["1221610"]}]},{"name":"ANID","award":["1171397"],"award-info":[{"award-number":["1171397"]}]},{"name":"ANID","award":["DI-02-24\/REG"],"award-info":[{"award-number":["DI-02-24\/REG"]}]},{"name":"ANID","award":["NCN17_093"],"award-info":[{"award-number":["NCN17_093"]}]},{"name":"ANID","award":["1220584"],"award-info":[{"award-number":["1220584"]}]},{"name":"ANID","award":["1221610"],"award-info":[{"award-number":["1221610"]}]},{"name":"Millennium Science Initiative Program","award":["1171397"],"award-info":[{"award-number":["1171397"]}]},{"name":"Millennium Science Initiative Program","award":["DI-02-24\/REG"],"award-info":[{"award-number":["DI-02-24\/REG"]}]},{"name":"Millennium Science Initiative Program","award":["NCN17_093"],"award-info":[{"award-number":["NCN17_093"]}]},{"name":"Millennium Science Initiative Program","award":["1220584"],"award-info":[{"award-number":["1220584"]}]},{"name":"Millennium Science Initiative Program","award":["1221610"],"award-info":[{"award-number":["1221610"]}]},{"name":"FONDECYT","award":["1171397"],"award-info":[{"award-number":["1171397"]}]},{"name":"FONDECYT","award":["DI-02-24\/REG"],"award-info":[{"award-number":["DI-02-24\/REG"]}]},{"name":"FONDECYT","award":["NCN17_093"],"award-info":[{"award-number":["NCN17_093"]}]},{"name":"FONDECYT","award":["1220584"],"award-info":[{"award-number":["1220584"]}]},{"name":"FONDECYT","award":["1221610"],"award-info":[{"award-number":["1221610"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Clostridioides difficile is a Gram-positive pathogen known for its toxin production and spore formation. It is primarily responsible for most cases of antibiotic-associated diarrhea. Bacterial persisters are a small subset of the population that exhibits transient tolerance to bactericidal substances, and they are of significant medical concern due to their association with the emergence of antibiotic resistance and difficult-to-treat chronic or recurrent infections. Vancomycin, the predominant antibiotic utilized in the management of C. difficile infection, is extensively applied in the realm of clinical practice. Previous studies have demonstrated a persister-like phenotype with treatments involving this antibiotic. However, the mechanism in C. difficile remains largely unknown, primarily due to the challenge of isolating this small population at any given time. To better characterize C. difficile persister cells, we present a study that enables the enrichment and characterization of persister cells from bacterial cultures in both the exponential and stationary phases. Moreover, we could differentiate between triggered (induced using antibiotics such as vancomycin) and spontaneous (stochastic) persister cells. Additionally, we observed the involvement of toxin-antitoxin systems and Clp proteases in persister cell formation.<\/jats:p>","DOI":"10.3390\/microorganisms12071394","type":"journal-article","created":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T13:22:36Z","timestamp":1720531356000},"page":"1394","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Characterization of Clostridioides difficile Persister Cells and Their Role in Antibiotic Tolerance"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5950-974X","authenticated-orcid":false,"given":"Osvaldo","family":"Inostroza","sequence":"first","affiliation":[{"name":"Microbiota-Host Interactions and Clostridia Research Group, Departamento de Ciencias Biol\u00f3gicas, Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago 8370186, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9374-0707","authenticated-orcid":false,"given":"Juan A.","family":"Fuentes","sequence":"additional","affiliation":[{"name":"Laboratorio de Gen\u00e9tica y Patog\u00e9nesis Bacteriana, Departamento de Ciencias Biol\u00f3gicas, Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago 8370186, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulina","family":"Y\u00e1\u00f1ez","sequence":"additional","affiliation":[{"name":"Microbiota-Host Interactions and Clostridia Research Group, Departamento de Ciencias Biol\u00f3gicas, Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago 8370186, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Espinoza","sequence":"additional","affiliation":[{"name":"Microbiota-Host Interactions and Clostridia Research Group, Departamento de Ciencias Biol\u00f3gicas, Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago 8370186, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Fica","sequence":"additional","affiliation":[{"name":"Microbiota-Host Interactions and Clostridia Research Group, Departamento de Ciencias Biol\u00f3gicas, Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago 8370186, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila","family":"Queralt\u00f3","sequence":"additional","affiliation":[{"name":"Microbiota-Host Interactions and Clostridia Research Group, Departamento de Ciencias Biol\u00f3gicas, Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago 8370186, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Microbiota-Host Interactions and Clostridia Research Group, Departamento de Ciencias Biol\u00f3gicas, Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago 8370186, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isidora","family":"Flores","sequence":"additional","affiliation":[{"name":"Microbiota-Host Interactions and Clostridia Research Group, Departamento de Ciencias Biol\u00f3gicas, Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago 8370186, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Microbiota-Host Interactions and Clostridia Research Group, Departamento de Ciencias Biol\u00f3gicas, Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago 8370186, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge A.","family":"Soto","sequence":"additional","affiliation":[{"name":"Millennium Institute on Immunology and Immunotherapy, Departamento de Ciencias Biol\u00f3gicas, Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago 8370186, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3554-0894","authenticated-orcid":false,"given":"Iv\u00e1n L.","family":"Calder\u00f3n","sequence":"additional","affiliation":[{"name":"Laboratorio de RNAs Bacterianos, Departamento de Ciencias Biol\u00f3gicas, Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago 8370186, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Gil","sequence":"additional","affiliation":[{"name":"Microbiota-Host Interactions and Clostridia Research Group, Departamento de Ciencias Biol\u00f3gicas, Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago 8370186, Chile"},{"name":"ANID-Millennium Science Initiative Program-Millennium Nucleus in the Biology of the Intestinal Microbiota, Santiago 8370186, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Zhu, D., Sorg, J.A., and Sun, X. (2018). Clostridioides difficile Biology: Sporulation, Germination, and Corresponding Therapies for C. difficile Infection. Front. Cell. Infect. Microbiol., 8.","DOI":"10.3389\/fcimb.2018.00029"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"237","DOI":"10.7861\/clinmedicine.18-3-237","article-title":"Clostridium difficile infection and antibiotic-associated diarrhoea","volume":"18","author":"Mullish","year":"2018","journal-title":"Clin. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1503\/cmaj.1031189","article-title":"Clostridium difficile-associated diarrhea in adults","volume":"171","author":"Poutanen","year":"2004","journal-title":"CMAJ Can. Med. Assoc. J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/mSphere.00045-15","article-title":"Antibiotic-Induced Alterations of the Gut Microbiota Alter Secondary Bile Acid Production and Allow for Clostridium difficile Spore Germination and Outgrowth in the Large Intestine","volume":"1","author":"Theriot","year":"2016","journal-title":"mSphere"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Edwards, A.N., Karim, S.T., Pascual, R.A., Jowhar, L.M., Anderson, S.E., and McBride, S.M. (2016). Chemical and Stress Resistances of Clostridium difficile Spores and Vegetative Cells. Front. Microbiol., 7.","DOI":"10.3389\/fmicb.2016.01698"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Ahmed, H., and Joshi, L.T. (2023). Clostridioides difficile spores tolerate disinfection with sodium hypochlorite disinfectant and remain viable within surgical scrubs and gown fabrics. Microbiology, 169.","DOI":"10.1099\/mic.0.001418"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S194","DOI":"10.1093\/infdis\/jiaa408","article-title":"Mechanisms of Colonization Resistance against Clostridioides difficile","volume":"223","author":"Pike","year":"2021","journal-title":"J. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Larsen, I.S., Chenaux, M., Collins, F.W., Mandic, A., Hansen, L.B., Lauridsen, C.A., Haller, R.F., Elvig-J\u00f8rgensen, S., Horwell, E., and Christiansen, J. (2023). Bacillus velezensis DSM 33864 reduces Clostridioides difficile colonization without disturbing commensal gut microbiota composition. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-42128-8"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"16","DOI":"10.5009\/gnl18071","article-title":"Recurrent Clostridium difficile Infection: Risk Factors, Treatment, and Prevention","volume":"13","author":"Song","year":"2019","journal-title":"Gut Liver"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"469","DOI":"10.2217\/fmb-2017-0203","article-title":"Clostridioides (Clostridium) difficile infection: Current and alternative therapeutic strategies","volume":"13","author":"Gil","year":"2018","journal-title":"Future Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e1029","DOI":"10.1093\/cid\/ciab549","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_12","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1002\/pro.3819","article-title":"Molecular mechanisms of vancomycin resistance","volume":"29","author":"Stogios","year":"2020","journal-title":"Protein Sci."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Normington, C., Moura, I.B., Bryant, J.A., Ewin, D.J., Clark, E.V., Kettle, M.J., Harris, H.C., Spittal, W., Davis, G., and Henn, M.R. (2021). Biofilms harbour Clostridioides difficile, serving as a reservoir for recurrent infection. npj Biofilms Microbiomes, 7.","DOI":"10.1038\/s41522-021-00184-w"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Soavelomandroso, A.P., Gaudin, F., Hoys, S., Nicolas, V., Vedantam, G., Janoir, C., and Bouttier, S. (2017). Biofilm Structures in a Mono-Associated Mouse Model of Clostridium difficile Infection. Front. Microbiol., 8.","DOI":"10.3389\/fmicb.2017.02086"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.jgar.2023.05.004","article-title":"The chaperone ClpC participates in sporulation, motility, biofilm, and toxin production of Clostridioides difficile","volume":"33","author":"Ortega","year":"2023","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"ref_16","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_17","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1146\/annurev.micro.112408.134306","article-title":"Persister cells","volume":"64","author":"Lewis","year":"2010","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1007\/s10541-005-0111-6","article-title":"Persister cells and the riddle of biofilm survival","volume":"70","author":"Lewis","year":"2005","journal-title":"Biochemistry. Biokhimiia"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1126\/science.1244705","article-title":"Internalization of Salmonella by macrophages induces formation of nonreplicating persisters","volume":"343","author":"Helaine","year":"2014","journal-title":"Science"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1126\/science.aat7148","article-title":"Salmonella persisters undermine host immune defenses during antibiotic treatment","volume":"362","author":"Stapels","year":"2018","journal-title":"Science"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Ca\u00f1as-Duarte, S.J., Restrepo, S., and Pedraza, J.M. (2014). Novel Protocol for Persister Cells Isolation. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0088660"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1534\/genetics.104.035352","article-title":"Bacterial persistence: A model of survival in changing environments","volume":"169","author":"Kussell","year":"2005","journal-title":"Genetics"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Willenborg, J., Willms, D., Bertram, R., Goethe, R., and Valentin-Weigand, P. (2014). Characterization of multi-drug tolerant persister cells in Streptococcus suis. BMC Microbiol., 14.","DOI":"10.1186\/1471-2180-14-120"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/978-1-4939-2854-5_7","article-title":"Quantitative Measurements of Type I and Type II Persisters Using ScanLag","volume":"1333","author":"Balaban","year":"2016","journal-title":"Methods Mol. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Balaban, N.Q., Healine, S., Lewis, K., Ackermann, M., Aldridge, B., Andersson, D.I., Brynildsen, M.P., Bumann, D., Camilli, A., and Collins, J.J. (2019). Publisher Correction: Definitions and guidelines for research on antibiotic persistence. Nat. Rev. Microbiol., 17.","DOI":"10.1038\/s41579-019-0207-4"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Kaus, G.M., Snyder, L.F., M\u00fch, U., Flores, M.J., Popham, D.L., and Ellermeier, C.D. (2020). Lysozyme Resistance in Clostridioides difficile Is Dependent on Two Peptidoglycan Deacetylases. J. Bacteriol., 202.","DOI":"10.1128\/JB.00421-20"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4191","DOI":"10.1074\/jbc.M113.510511","article-title":"MazF-induced growth inhibition and persister generation in Escherichia coli","volume":"289","author":"Tripathi","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1016\/S1097-2765(03)00402-7","article-title":"MazF Cleaves Cellular mRNAs Specifically at ACA to Block Protein Synthesis in Escherichia coli","volume":"12","author":"Zhang","year":"2003","journal-title":"Mol. Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1128\/JB.06628-11","article-title":"RelE-mediated dormancy is enhanced at high cell density in Escherichia coli","volume":"194","author":"Tashiro","year":"2012","journal-title":"J. Bacteriol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Zhao, Y., McAnulty, M.J., and Wood, T.K. (2016). Toxin YafQ Reduces Escherichia coli Growth at Low Temperatures. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0161577"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1111\/1462-2920.12567","article-title":"Toxin YafQ increases persister cell formation by reducing indole signalling","volume":"17","author":"Hu","year":"2015","journal-title":"Environ. Microbiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2396","DOI":"10.1093\/jac\/dky186","article-title":"Effect of antibiotic treatment on the formation of non-spore Clostridium difficile persister-like cells","volume":"73","author":"Inostroza","year":"2018","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"\u00c1lvarez, R., Ortega-Fuentes, C., Queralt\u00f3, C., Inostroza, O., D\u00edaz-Y\u00e1\u00f1ez, F., Gonz\u00e1lez, R., Calder\u00f3n, I.L., Fuentes, J.A., Paredes-Sabja, D., and Gil, F. (2020). Evaluation of functionality of type II toxin-antitoxin systems of Clostridioides difficile R20291. Microbiol. Res., 239.","DOI":"10.1016\/j.micres.2020.126539"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4398","DOI":"10.1128\/AAC.00372-13","article-title":"Establishment of a method to rapidly assay bacterial persister metabolism","volume":"57","author":"Orman","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Pe\u00f1aloza, D., Acu\u00f1a, L.G., Barros, M.J., N\u00fa\u00f1ez, P., Montt, F., Gil, F., Fuentes, J.A., and Calder\u00f3n, I.L. (2021). The Small RNA RyhB Homologs from Salmonella Typhimurium Restrain the Intracellular Growth and Modulate the SPI-1 Gene Expression within RAW264.7 Macrophages. Microorganisms, 9.","DOI":"10.3390\/microorganisms9030635"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0378-1097(03)00856-5","article-title":"Persister cells and tolerance to antimicrobials","volume":"230","author":"Keren","year":"2004","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s12275-019-8629-2","article-title":"Ribosome dependence of persister cell formation and resuscitation","volume":"57","author":"Wood","year":"2019","journal-title":"J. Microbiol."},{"key":"ref_38","first-page":"23","article-title":"Recent advances in the understanding of antibiotic resistance in Clostridium difficile infection","volume":"3","author":"Spigaglia","year":"2016","journal-title":"Ther. Adv. Infect. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.ijid.2020.11.004","article-title":"Fidaxomicin versus metronidazole, vancomycin and their combination for initial episode, first recurrence and severe Clostridioides difficile infection\u2014An observational cohort study","volume":"103","author":"Polivkova","year":"2021","journal-title":"Int. J. Infect. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Chowdhury, N., Kwan, B.W., and Wood, T.K. (2016). Persistence Increases in the Absence of the Alarmone Guanosine Tetraphosphate by Reducing Cell Growth. Sci. Rep., 6.","DOI":"10.1038\/srep20519"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.tim.2014.04.003","article-title":"Clostridium difficile spore biology: Sporulation, germination, and spore structural proteins","volume":"22","author":"Shen","year":"2014","journal-title":"Trends Microbiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"10701","DOI":"10.1093\/nar\/gks864","article-title":"Global transcriptional control by glucose and carbon regulator CcpA in Clostridium difficile","volume":"40","author":"Antunes","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Li, J., and Zhao, X. (2020). Effects of quorum sensing on the biofilm formation and viable but non-culturable state. Food Res. Int., 137.","DOI":"10.1016\/j.foodres.2020.109742"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"397","DOI":"10.4161\/gmic.25862","article-title":"Biofilm formation by Clostridium difficile","volume":"4","author":"Dapa","year":"2013","journal-title":"Gut Microbes"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1038\/nchembio.2044","article-title":"Toxin-antitoxin systems in bacterial growth arrest and persistence","volume":"12","author":"Page","year":"2016","journal-title":"Nat. Chem. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Mohiuddin, S.G., Massahi, A., and Orman, M.A. (2022). lon Deletion Impairs Persister Cell Resuscitation in Escherichia coli. mBio, 13.","DOI":"10.1128\/mbio.02187-21"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1111\/j.1365-2958.2009.06969.x","article-title":"Three new RelE-homologous mRNA interferases of Escherichia coli differentially induced by environmental stresses","volume":"75","author":"Gerdes","year":"2010","journal-title":"Mol. Microbiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1099\/jmm.0.000304","article-title":"Effect of clpP and clpC deletion on persister cell number in Staphylococcus aureus","volume":"65","author":"Springer","year":"2016","journal-title":"J. Med. Microbiol."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/12\/7\/1394\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:12:16Z","timestamp":1760109136000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/12\/7\/1394"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,9]]},"references-count":48,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["microorganisms12071394"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms12071394","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,9]]}}}