{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T19:32:08Z","timestamp":1785785528920,"version":"3.56.0"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T00:00:00Z","timestamp":1745971200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:p><jats:italic>Proteus mirabilis<\/jats:italic>, an important zoonotic opportunistic pathogen, is widely found in nature and the intestinal tracts of animals, which can cause diarrhea, pneumonia, urinary tract infections, and other symptoms in domestic animals including sheep, pigs, cattle and chickens. In this study, necropsy of a deceased critically endangered Malayan pangolin revealed lobar pneumonia in the lungs and hepatocyte necrosis with hepatic cord disintegration in the liver. A strain of <jats:italic>Proteus mirabilis<\/jats:italic> (PM2022) was isolated from the affected lungs and liver. This bacterium exhibited multidrug resistance, being susceptible only to cefoxitin and amikacin. Whole-genome sequencing identified 26 antibiotic resistance genes, including <jats:italic>CTX-M-65<\/jats:italic>, <jats:italic>FosA3<\/jats:italic>, which mediate resistance to five classes of antibiotics, such as penicillins and quinolones. Additionally, 20 virulence factors (including the T6SS secretion system, hemolysins HpmA\/B, among others) were detected. Mouse experiments confirmed its high pathogenicity (LD<jats:sub>50<\/jats:sub> =\u202f1.45\u202f\u00d7\u202f10<jats:sup>9<\/jats:sup> CFU\/mL). Based on experimental and genomic testing results, the initial symptoms of <jats:italic>Proteus mirabilis<\/jats:italic> infection in pangolins manifest in the lungs, liver, and intestines, and the use of penicillins and quinolones should be avoided during treatment. This study offers clinical guidance for diagnosing and treating <jats:italic>P. mirabilis<\/jats:italic> infections in pangolins, informing evidence-based antimicrobial strategies.<\/jats:p>","DOI":"10.3389\/fvets.2025.1552499","type":"journal-article","created":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T05:42:50Z","timestamp":1745991770000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Multidrug-resistant Proteus mirabilis in a critically endangered Malayan pangolin: clinical and genomic insights"],"prefix":"10.3389","volume":"12","author":[{"given":"Ziqiao","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuyu","family":"An","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shasha","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haikuo","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Hua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,30]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"e02962","DOI":"10.1016\/j.gecco.2024.e02962","article-title":"Mapping the distribution of the Sunda pangolin (Manis javanica) within natural forest in Sabah, Malaysian Borneo","volume":"52","author":"Panjang","year":"2024","journal-title":"Glob Ecol Conserv"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"271","DOI":"10.3724\/SP.J.1141.2012.03271","article-title":"Allometry of scales in Chinese pangolins (Manis pentadactyla) and Malayan pangolins (Manis javanica) and application in judicial expertise","volume":"33","author":"Zhou","year":"2012","journal-title":"Zool Res"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1002\/pan3.10150","article-title":"Knowledge and attitudes about the use of pangolin scale products in traditional Chinese medicine (TCM) within China","volume":"2","author":"Wang","year":"2020","journal-title":"People Nat"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"99","DOI":"10.3897\/zookeys.507.6970","article-title":"Captive breeding of pangolins: current status, problems and future prospects","volume":"507","author":"Hua","year":"2015","journal-title":"Zookeys"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1083\/jcb.31.3.585","article-title":"Basal bodies of bacterial flagella in Proteus mirabilis. I. Electron microscopy of sectioned material","volume":"31","author":"Van Iterson","year":"1966","journal-title":"J Cell Biol"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1007\/s42770-019-00086-2","article-title":"Genotypic and phenotypic profiles of virulence factors and antimicrobial resistance of Proteus mirabilis isolated from chicken carcasses: potential zoonotic risk","volume":"50","author":"Sanches","year":"2019","journal-title":"Braz J Microbiol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"109","DOI":"10.3969\/j.issn.1005-7021.2019.01.017","article-title":"Research progress on virulence factors of Proteus mirabilis","volume":"39","author":"Chen","year":"2019","journal-title":"J Microbiol"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"916","DOI":"10.13344\/j.microbiol.china.200480","article-title":"Research progress in transmission of multidrug resistance mediated by genomic islands in Proteus mirabilis","volume":"48","author":"Li","year":"2021","journal-title":"Microbiol China"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1111\/1749-4877.12510","article-title":"Multidrug-resistant Proteus mirabilis isolates carrying blaOXA-1 and blaNDM-1 from wildlife in China: increasing public health risk","volume":"16","author":"Kang","year":"2021","journal-title":"Integr Zool"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.UTI-0017-2013","article-title":"Proteus mirabilis and urinary tract infections","volume":"3","author":"Schaffer","year":"2015","journal-title":"Microbiol Spectr"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"2562","DOI":"10.1002\/vms3.926","article-title":"Pyoderma caused by Proteus mirabilis in sheep","volume":"8","author":"Abdollahi","year":"2022","journal-title":"Vet Med Sci"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"952982","DOI":"10.3389\/fmicb.2022.952982","article-title":"Genomic investigation of Proteus mirabilis isolates recovered from pig farms in Zhejiang Province, China","volume":"13","author":"Qu","year":"2022","journal-title":"Front Microbiol"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1292\/jvms.15-0636","article-title":"Necrotizing suppurative nephritis in a Japanese black feedlot steer due to Proteus mirabilis infection","volume":"79","author":"Abe","year":"2017","journal-title":"J Vet Med Sci"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"629","DOI":"10.12101\/j.issn.1004-390X(n).201910011","article-title":"Isolation, identification and drug resistance analysis of Proteus mirabilis from dairy cow","volume":"35","author":"Chen","year":"2020","journal-title":"J Yunnan Agric Univ"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1353","DOI":"10.1007\/s42770-020-00240-1","article-title":"Proteus mirabilis causing cellulitis in broiler chickens","volume":"51","author":"Sanches","year":"2020","journal-title":"Braz J Microbiol"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"69","DOI":"10.16656\/j.issn.1673-4696.2018.0011","article-title":"Isolation, identification, and phylogenetic analysis of Proteus mirabilis from South China tiger","volume":"48","author":"Fan","year":"2018","journal-title":"Chin Vet Sci"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.19711\/j.cnki.issn2310-1490.2020.04.023","article-title":"A case of Klebsiella pneumoniae and Proteus mirabilis infection in giant panda (Ailuropoda melanoleuca)","volume":"41","author":"Chen","year":"2020","journal-title":"Chin J Wildlife"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"20","DOI":"10.3969\/j.issn.1002-5235.2021.03.002","article-title":"Proteus mirabilis causes acute diarrhea in red pandas","volume":"5","author":"Xiu","year":"2005","journal-title":"Fujian J Anim Husb Vet Med"},{"key":"ref19","first-page":"102","article-title":"Isolation, cultivation, and identification of bacteria from the intestine of dead Malayan pangolins","volume":"37","author":"He","year":"2021","journal-title":"Guangxi J Anim Husb Vet Med"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.jcpa.2021.03.003","article-title":"Pyelonephritis and cystic endometrial hyperplasia in a captive Sunda pangolin (Manis javanica)","volume":"184","author":"Chong","year":"2021","journal-title":"J Comp Pathol"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"657","DOI":"10.12375\/ysdwxb.20230321","article-title":"Isolation, identification, and biological characteristics analysis of one Proteus mirabilis strain from wild Manis javanica","volume":"44","author":"Liu","year":"2023","journal-title":"Chin J Wildlife"},{"key":"ref22","volume-title":"Molecular cloning: a laboratory manual","author":"Sambrook","year":"2001"},{"key":"ref23","volume-title":"Performance standards for antimicrobial susceptibility testing","year":"2023"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"714","DOI":"10.1021\/es60130a004","article-title":"Trimmed spearman-Karber method for estimating median lethal concentrations in toxicity bioassays","volume":"11","author":"Hamilton","year":"1977","journal-title":"Environ Sci Technol"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1038\/nrg2626","article-title":"Sequencing technologies-the next generation","volume":"11","author":"Metzker","year":"2010","journal-title":"Nat Rev Genet"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1111\/j.1469-0691.2011.03570.x","article-title":"Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance","volume":"18","author":"Magiorakos","year":"2012","journal-title":"Clin Microbiol Infect"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"589","DOI":"10.3389\/fvets.2020.00589","article-title":"Biological characteristics and genetic analysis of a highly pathogenic Proteus Mirabilis strain isolated from dogs in China","volume":"7","author":"Hu","year":"2020","journal-title":"Front Vet Sci"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"D912","DOI":"10.1093\/nar\/gkab1107","article-title":"VFDB 2022: a general classification scheme for bacterial virulence factors","volume":"50","author":"Liu","year":"2022","journal-title":"Nucleic Acids Res"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"102","DOI":"10.16303\/j.cnki.1005-4545.2020.01.18","article-title":"Isolation and identification of bacteria from pangolin Malay with multiple bacteria infection and toxicity test in mice","volume":"40","author":"Zhang","year":"2020","journal-title":"Chin J Vet Sci"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"72","DOI":"10.3969\/j.issn.1673-1182.2023.09.013","article-title":"Isolation, identification, pathogenicity, and drug resistance of Proteus mirabilis diarrhea in raccoon dogs","volume":"44","author":"Shi","year":"2023","journal-title":"J Domest Anim Ecol"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"e0241321","DOI":"10.1128\/jcm.02413-21","article-title":"The brief case: Proteus mirabilis causing Coraliform Lithiasis and bacteremia in an elderly catheterized patient","volume":"60","author":"Maldonado-Barrueco","year":"2022","journal-title":"J Clin Microbiol"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"1799","DOI":"10.1093\/jac\/dkz107","article-title":"Characterization of a blaIMP-4-carrying plasmid from Enterobacter cloacae of swine origin","volume":"74","author":"Zhu","year":"2019","journal-title":"J Antimicrob Chemother"},{"key":"ref33","first-page":"252","article-title":"Clinical significance of Proteus mirabilis bacteriuria in dogs, risk factors and antimicrobial susceptibility","volume":"84","author":"Dec\u00f4me","year":"2020","journal-title":"Can J Vet Res"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"3030","DOI":"10.16431\/j.cnki.1671-7236.2024.07.028","article-title":"Whole genome sequencing and virulence and drug resistance analysis of a strain of Proteus mirabilis derived from peacock","volume":"51","author":"Jiao","year":"2024","journal-title":"China Anim Husb Vet Med"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"2569","DOI":"10.13344\/j.microbiol.china.230006","article-title":"Whole-genome sequencing, virulence, and drug resistance of a bovine-derived strain of Salmonella enterica subsp. enterica serovar Dublin","volume":"50","author":"Li","year":"2023","journal-title":"Microbiol China"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"127768","DOI":"10.1016\/j.chemosphere.2020.127768","article-title":"Distribution characteristics and potential risks of heavy metals and antimicrobial resistant Escherichia coli in dairy farm wastewater in Tai\u2019an, China","volume":"262","author":"Liu","year":"2021","journal-title":"Chemosphere"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1016\/j.psj.2019.10.044","article-title":"Prevalence and characteristics of multidrug-resistant mcr-1-positive Escherichia coli isolates from broiler chickens in Tai\u2019an","volume":"99","author":"Song","year":"2020","journal-title":"China"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.cmi.2016.11.012","article-title":"The role of whole genome sequencing in antimicrobial susceptibility testing of bacteria: report from the EUCAST subcommittee","volume":"23","author":"Ellington","year":"2017","journal-title":"Clin Microbiol Infect"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"e0005019","DOI":"10.1128\/CMR.00050-19","article-title":"Evolutionary pathways and trajectories in antibiotic resistance","volume":"34","author":"Baquero","year":"2021","journal-title":"Clin Microbiol Rev"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"1234","DOI":"10.16656\/j.issn.1673-4696.2017.10.005","article-title":"Isolation, identification, and toxicity test of Proteus mirabilis from swine","volume":"47","author":"Ma","year":"2017","journal-title":"Chin Vet Sci"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"1","DOI":"10.13344\/j.microbiol.china.240699","article-title":"Isolation, identification, and characterization of sika deer-derived Proteus mirabilis","author":"Cao","year":"2024","journal-title":"Microbiol China"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"e2104813118","DOI":"10.1073\/pnas.2104813118","article-title":"Sensing of intracellular hcp levels controls T6SS expression in Vibrio cholerae","volume":"118","author":"Manera","year":"2021","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1007\/s11427-022-2172-x","article-title":"SecReT6 update: a comprehensive resource of bacterial type VI secretion systems","volume":"66","author":"Zhang","year":"2023","journal-title":"Sci China Life Sci"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"1206","DOI":"10.1128\/jb.172.3.1206-1216.1990","article-title":"Nucleotide sequencing of the Proteus mirabilis calcium-independent hemolysin genes (hpmA and hpmB) reveals sequence similarity with the Serratia marcescens hemolysin genes (shlA and shlB)","volume":"172","author":"Uphoff","year":"1990","journal-title":"J Bacteriol"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"5159","DOI":"10.1128\/IAI.72.9.5159-5167.2004","article-title":"Proteus mirabilis ZapA metalloprotease degrades a broad spectrum of substrates, including antimicrobial peptides","volume":"72","author":"Belas","year":"2004","journal-title":"Infect Immun"}],"container-title":["Frontiers in Veterinary Science"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2025.1552499\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T05:43:03Z","timestamp":1745991783000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2025.1552499\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,30]]},"references-count":45,"alternative-id":["10.3389\/fvets.2025.1552499"],"URL":"https:\/\/doi.org\/10.3389\/fvets.2025.1552499","relation":{},"ISSN":["2297-1769"],"issn-type":[{"value":"2297-1769","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,30]]},"article-number":"1552499"}}