{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T11:37:30Z","timestamp":1789213050188,"version":"build-2803163510"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T00:00:00Z","timestamp":1764720000000},"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. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The rise of antimicrobial resistance (AMR) in\n                      <jats:italic>Salmonella enterica<\/jats:italic>\n                      serovar Typhi poses a serious threat to global enteric fever control. In particular, the emergence of resistance to third-generation cephalosporins and azithromycin critically undermines available treatment options. Sustained genomic surveillance of high-risk\n                      <jats:italic>S<\/jats:italic>\n                      . Typhi lineages and resistance determinants is essential for informing antibiotic policy and optimizing typhoid conjugate vaccine (TCV) introduction in endemic regions. In this study, we report a multicenter outbreak of carbapenem-resistant\n                      <jats:italic>S<\/jats:italic>\n                      . Typhi in India and investigate its genomic epidemiology, resistance mechanisms, and evolutionary origins.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A total of 31 carbapenem-resistant\n                      <jats:italic>S<\/jats:italic>\n                      . Typhi isolates collected from multiple tertiary care hospitals were subjected to phenotypic antimicrobial susceptibility testing and whole-genome sequencing (WGS). Short-read WGS data were used to analyze core-genome SNPs, infer phylogenetic relationships, and investigate AMR determinants. Two representative isolates underwent long-read Oxford Nanopore sequencing for plasmid reconstruction and comparative genomic analysis with Enterobacterales.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Antimicrobial susceptibility testing of isolates revealed resistance to ampicillin, ciprofloxacin, ceftriaxone, and carbapenems while retaining susceptibility to chloramphenicol, cotrimoxazole, and azithromycin. The genomic analysis identified the presence of two plasmids: IncFIB(K) harboring\n                      <jats:italic>bla<\/jats:italic>\n                      <jats:sub>CTX-M-15<\/jats:sub>\n                      ,\n                      <jats:italic>qnrS1<\/jats:italic>\n                      ,\n                      <jats:italic>tetA<\/jats:italic>\n                      , and IncX3, carrying the\n                      <jats:italic>bla<\/jats:italic>\n                      <jats:sub>NDM-5<\/jats:sub>\n                      gene. Phylogenetic analysis classified the isolates within a novel genotype, 4.3.1.1.1, belonging to genotype 4.3.1.1 (H58 lineage I). Notably, plasmid comparison revealed high similarity to resistance plasmids circulating in co-endemic\n                      <jats:italic>Escherichia coli<\/jats:italic>\n                      and\n                      <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                      , indicating recent horizontal gene transfer.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This is the first documented outbreak of\n                      <jats:italic>bla<\/jats:italic>\n                      <jats:sub>NDM<\/jats:sub>\n                      -mediated carbapenem-resistant\n                      <jats:italic>S<\/jats:italic>\n                      . Typhi, highlighting a new stage in the evolution of drug-resistant typhoid. The acquisition of high-risk plasmids by\n                      <jats:italic>S<\/jats:italic>\n                      . Typhi and their integration into successful epidemic lineages underscores the urgent need for strengthened genomic surveillance and inter-species AMR tracking. Our findings have direct implications for treatment guidelines, TCV implementation strategies, and efforts to prevent global dissemination of carbapenem-resistant\n                      <jats:italic>S<\/jats:italic>\n                      . Typhi.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2025.1685068","type":"journal-article","created":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T06:39:19Z","timestamp":1764743959000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Emergence of carbapenem-resistant Salmonella Typhi harboring blaNDM-5 in India: genomic evidence from a multicenter study"],"prefix":"10.3389","volume":"16","author":[{"given":"Tharani Priya","family":"Thirumoorthy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jobin John","family":"Jacob","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monisha Priya","family":"Teekaraman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Mahantesh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhavana","family":"Jagannatha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suhani","family":"Manasa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Savitha","family":"Nagaraj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayanthi","family":"Savio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyadarshini A.","family":"Padaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Sudarsana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashalatha","family":"Nair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sukanya","family":"Verma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raman","family":"Gaikwad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Divya","family":"Joshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasant C.","family":"Nagvekar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Rodrigues","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavithra Sathya","family":"Narayanan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aravind","family":"Velmurugan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. 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