{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T12:03:15Z","timestamp":1791460995986,"version":"4.3.4"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013919","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:00:00Z","timestamp":1770336000000}}],"reference-count":53,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015691","name":"Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI143704"],"award-info":[{"award-number":["R01AI143704"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01GM130971"],"award-info":[{"award-number":["R01GM130971"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R35GM148351"],"award-info":[{"award-number":["R35GM148351"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Antibiotic tolerance is the ability of bacteria to survive normally lethal doses of antibiotics for extended time periods. Clinically significant Enterobacterales, for example, can exhibit high tolerance to the last-resort antibiotic meropenem. Meropenem tolerance is associated with formation of cell wall-deficient spheroplasts that readily recover to rod shape and normal growth upon removal of the antibiotic. Both the true prevalence of tolerance, and genetic mechanisms underlying it, remain poorly understood. Here, we find that meropenem tolerance is widespread among clinical Enterobacterales. Using forward genetics, we uncover tolerance factors in a hypertolerant isolate of the ESKAPE pathogen\n                    <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                    . We find that multiple mechanisms contribute to tolerance, and that cell envelope stress responses (PhoPQ, CpxPRA, Rcs phosphorelay\u00a0and OmpR\/EnvZ) collectively promote spheroplast stability and recovery, while the lytic transglycosylase MltB counteracts it. Our data indicate that tolerance is widespread among clinical isolates, and that outer membrane maintenance is a key factor promoting survival of tolerant\n                    <jats:italic>K. pneumoniae.<\/jats:italic>\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1013919","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T18:44:56Z","timestamp":1769798696000},"page":"e1013919","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Prevalence and mechanisms of high-level carbapenem antibiotic tolerance in clinical isolates of Klebsiella pneumoniae"],"prefix":"10.1371","volume":"22","author":[{"given":"Trevor","family":"Cross","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Facundo","family":"Torres","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Nikulin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail P.","family":"McGee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leena","family":"Jalees","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhea","family":"Balakrishnan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tolani","family":"Aliyu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars 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