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those that are resistant to meropenem but susceptible to ertapenem, adding further complexity to the clinical landscape. This study investigates the emergence of ertapenem-resistant, meropenem-susceptible (ErMs) Escherichia coli and Klebsiella pneumoniae CRE across five hospitals in San Antonio, Texas, USA, from 2012 to 2018. The majority of the CRE isolates were non-carbapenemase producers (NCP; 54%; 41\/76); 56% of all NCP isolates had an ErMs phenotype. Among ErMs strains, E. coli comprised the majority (72%). ErMs strains carrying blaCTX-M had, on average, 9-fold higher copies of blaCTX-M than CP-ErMs strains as well as approximately 4-fold more copies than blaCTX-M-positive but ertapenem- and meropenem-susceptible (EsMs) strains (3.7 vs. 0.9, p &lt; 0.001). Notably, carbapenem hydrolysis was observed to be mediated by strains harboring blaCTX-M with and without a carbapenemase(s). ErMs also carried more mobile genetic elements, particularly IS26 composite transposons, than EsMs (37 vs. 0.2, p &lt; 0.0001). MGE- ISVsa5 was uniquely more abundant in ErMs than either EsMs or ErMr strains, with over 30 more average ISVsa5 counts than both phenotype groups (p &lt; 0.0001). Immunoblot analysis demonstrated the absence of OmpC expression in NCP-ErMs E. coli, with 92% of strains lacking full contig coverage of ompC. Overall, our findings characterize both collaborative and independent efforts between blaCTX-M and OmpC in ErMs strains, indicating the need to reappraise the term \u201cnon-carbapenemase (NCP)\u201d, particularly for strains highly expressing blaCTX-M. To improve outcomes for CRE-infected patients, future efforts should focus on mechanisms underlying the emerging ErMs subphenotype of CRE strains to develop technologies for its rapid detection and provide targeted therapeutic strategies.<\/jats:p>","DOI":"10.3390\/antibiotics13020185","type":"journal-article","created":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T04:18:22Z","timestamp":1707884302000},"page":"185","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Diverse Role of blaCTX-M and Porins in Mediating Ertapenem Resistance among Carbapenem-Resistant Enterobacterales"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0020-0216","authenticated-orcid":false,"given":"Cody A.","family":"Black","sequence":"first","affiliation":[{"name":"College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA"},{"name":"Joe R. and Teresa Lozano Long School of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond","family":"Benavides","sequence":"additional","affiliation":[{"name":"College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA"},{"name":"Joe R. and Teresa Lozano Long School of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah M.","family":"Bandy","sequence":"additional","affiliation":[{"name":"College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA"},{"name":"Joe R. and Teresa Lozano Long School of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven D.","family":"Dallas","sequence":"additional","affiliation":[{"name":"Joe R. and Teresa Lozano Long School of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA"},{"name":"Department of Pathology and Laboratory Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA"},{"name":"University Health System, San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard","family":"Gawrys","sequence":"additional","affiliation":[{"name":"College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA"},{"name":"Joe R. and Teresa Lozano Long School of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA"},{"name":"University Health System, San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wonhee","family":"So","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvaro G.","family":"Moreira","sequence":"additional","affiliation":[{"name":"Joe R. and Teresa Lozano Long School of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA"},{"name":"Veterans Administration Research Center for AIDS and HIV-1 Infection and Center for Personalized Medicine, South Texas Veterans Health Care System, San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Aguilar","sequence":"additional","affiliation":[{"name":"College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA"},{"name":"Joe R. and Teresa Lozano Long School of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA"},{"name":"University Health System, San Antonio, TX 78229, 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Texas at Austin, Austin, TX 78712, USA"},{"name":"Joe R. and Teresa Lozano Long School of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0692-4787","authenticated-orcid":false,"given":"Christopher R.","family":"Frei","sequence":"additional","affiliation":[{"name":"College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA"},{"name":"Joe R. and Teresa Lozano Long School of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA"},{"name":"University Health System, San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jim M.","family":"Koeller","sequence":"additional","affiliation":[{"name":"College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA"},{"name":"Joe R. and Teresa Lozano Long School of Medicine, The University 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