{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T03:41:53Z","timestamp":1794368513768,"version":"4.9.0"},"posted":{"date-parts":[[2025,11,22]]},"group-title":"Microbiology","reference-count":92,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T00:00:00Z","timestamp":1763769600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01 DK123158"],"award-info":[{"award-number":["R01 DK123158"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01 DK140371"],"award-info":[{"award-number":["R01 DK140371"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"crossref","award":["24PRE1195538"],"award-info":[{"award-number":["24PRE1195538"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Urinary tract infections (UTIs) impose a large healthcare burden, with escalating antimicrobial resistance (AMR) and treatment failure.\n                  <jats:italic>Proteus mirabilis<\/jats:italic>\n                  is an under-characterized and challenging UTI pathogen due to intrinsic resistances and biofilm formation. To understand\n                  <jats:italic>P. mirabilis<\/jats:italic>\n                  population genomics, we combined pangenome analysis,\n                  <jats:italic>in silico<\/jats:italic>\n                  AMR predication, and phenotypic antimicrobial susceptibility testing (AST) across 1,027\n                  <jats:italic>P. mirabilis<\/jats:italic>\n                  genomes derived from human urine specimens. This revealed a mosaic pangenome driven by extensive accessory genome plasticity. Multilocus sequence typing (MLST) identified 213 MLSTs with only 7% having \u226510 genomes, highlighting strain diversity. AMR gene profiles were largely lineage specific, with 25% of genomes harboring resistances for &gt;6 antimicrobial subclasses. ST135 was identified as a highly MDR lineage, with 95% of genomes carrying \u226516 resistance genes. Mobile genetic element (MGE) analysis of 22 clinical isolates with complete, reference level genomes revealed that Tn7 transposons, IS26-mediated genomic islands, and class 1 integrons act as vehicles for high AMR gene dissemination, including IS26-mediated gene stacking within a\n                  <jats:italic>Proteus mirabilis<\/jats:italic>\n                  Genomic Resistance Island 1 (\n                  <jats:italic>PmGRI1)<\/jats:italic>\n                  in ST135 isolates. While presence of genes like\n                  <jats:italic>aph(3\u2019)-la<\/jats:italic>\n                  reliably predicted kanamycin resistance, discordance for antibiotics such as trimethoprim-sulfamethoxazole and chloramphenicol revealed that AMR gene stacking, regulatory context, and intrinsic mechanisms, like efflux pumps, modulate phenotypic outcomes. In summary, our study provides a comprehensive and phenotypic resolution of\n                  <jats:italic>P. mirabilis<\/jats:italic>\n                  AMR, establishing that resistance architecture is lineage structured, MGE-driven, and phenotypically non-deterministic. We emphasize the need to shift towards standardized, genome-informed surveillance framework to translate into diagnostic and therapeutic strategies.\n                <\/jats:p>","DOI":"10.1101\/2025.11.21.689858","type":"posted-content","created":{"date-parts":[[2025,11,23]],"date-time":"2025-11-23T01:40:17Z","timestamp":1763862017000},"source":"Crossref","is-referenced-by-count":5,"title":["Pangenome Analysis of\n                  <i>Proteus mirabilis<\/i>\n                  Reveals Lineage-Specific Antimicrobial Resistance Profiles and Discordant Genotype-Phenotype Correlations"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1488-1569","authenticated-orcid":false,"given":"Namrata","family":"Deka","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY, 14203, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aimee L.","family":"Brauer","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY, 14203, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Connerton","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY, 14203, NY, USA"},{"name":"School of Nursing, Niagara University, Buffalo, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2949-7818","authenticated-orcid":false,"given":"Blake M.","family":"Hanson","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, UTHealth Houston School of Public Health"},{"name":"Center for Infectious Diseases, UTHealth Houston School of Public Health"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0079-3261","authenticated-orcid":false,"given":"Jennifer N.","family":"Walker","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, McGovern Medical School, The University of Texas Health Science Center at Houston, Texas, USA"},{"name":"Department of Epidemiology, UTHealth Houston School of Public Health"},{"name":"Center for Infectious Diseases, UTHealth Houston School of Public Health"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2165-2759","authenticated-orcid":false,"given":"Chelsie E.","family":"Armbruster","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY, 14203, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041020200838000_2025.11.21.689858v3.1","doi-asserted-by":"crossref","first-page":"888205","DOI":"10.3389\/fpubh.2022.888205","article-title":"Disease burden and long-term trends of urinary tract infections: A worldwide report","volume":"10","year":"2022","journal-title":"Front Public Health"},{"key":"2026041020200838000_2025.11.21.689858v3.2","doi-asserted-by":"publisher","DOI":"10.1007\/s00345-021-03913-0"},{"key":"2026041020200838000_2025.11.21.689858v3.3","doi-asserted-by":"crossref","unstructured":"Biondo, C ., New Insights into the Pathogenesis and Treatment of Urinary Tract Infections. 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