{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:39:54Z","timestamp":1791319194082,"version":"4.3.1"},"reference-count":87,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T00:00:00Z","timestamp":1740441600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>The management of infectious diseases has proven to be a daunting task for clinicians worldwide, and the rapid development of antibiotic resistance among Gram-negative bacteria is making it even more challenging. The first-line therapy is empirical, and it most often comprises \u03b2-lactam antibiotics. Among Gram-negative bacteria, Proteus mirabilis, an important community and hospital pathogen associated primarily with urinary tract and wound infection, holds a special place. This review\u2019s aim was to collate and examine recent studies investigating \u03b2-lactam resistance phenotypes and mechanisms of Proteus species and the global significance of its \u03b2-lactam resistance evolution. Moreover, the genetic background of resistance traits and the role of mobile genetic elements in the dissemination of resistance genes were evaluated. P. mirabilis as the dominant pathogen develops resistance to expanded-spectrum cephalosporins (ESC) by producing extended-spectrum \u03b2-lactamases (ESBL) and plasmid-mediated AmpC \u03b2-lactamases (p-AmpC). \u03b2-lactamase-mediated resistance to carbapenems in Enterobacterales, including Proteus spp., is mostly due to expression of carbapenemases of class A (KPC); class B (metallo-\u03b2-lactamases or MBLs of IMP, VIM, or NDM series); or class D or carbapenem-hydrolyzing oxacillinases (CHDL). Previously, a dominant ESBL type in P. mirabilis was TEM-52; yet, lately, it has been replaced by CTX-M variants, particularly CTX-M-14. ESC resistance can also be mediated by p-AmpC, with CMY-16 as the dominant variant. Carbapenem resistance in Proteus spp. is a challenge due to its intrinsic resistance to colistin and tigecyclin. The first carbapenemases reported belonged to class B, most frequently VIM-1 and NDM-5. In Europe, predominantly France and Belgium, a clonal lineage positive for OXA-23 CHDL spreads rapidly undetected, due to its low-level resistance to carbapenems. The amazing capacity of Proteus spp. to accumulate a plethora of various resistance traits is leading to multidrug or extensively drug-resistant phenotypes.<\/jats:p>","DOI":"10.3390\/microorganisms13030508","type":"journal-article","created":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T12:01:17Z","timestamp":1740484877000},"page":"508","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Evolution of \u03b2-Lactam Antibiotic Resistance in Proteus Species: From Extended-Spectrum and Plasmid-Mediated AmpC \u03b2-Lactamases to Carbapenemases"],"prefix":"10.3390","volume":"13","author":[{"given":"Branka","family":"Bedeni\u0107","sequence":"first","affiliation":[{"name":"Biomedical Research Center \u0160alata, University of Zagreb School of Medicine, Department for Clinical Microbiology and Infection Prevention and Control, University Hospital Centre Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9462-2593","authenticated-orcid":false,"given":"Mladen","family":"Pospi\u0161il","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, University Hospital Centre Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Na\u0111","sequence":"additional","affiliation":[{"name":"University of Zagreb School of Medicine, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0529-8657","authenticated-orcid":false,"given":"Daniela","family":"Bandi\u0107 Pavlovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care, University of Zagreb School of Medicine, University Hospital Centre Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1128\/CMR.14.4.933-951.2001","article-title":"Extended-spectrum \u03b2-lactamases in the 21st Century: Characterization, Epidemiology, and Detection of This Important Resistance Threat","volume":"14","author":"Bradford","year":"2001","journal-title":"Clin. 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