{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T06:25:28Z","timestamp":1793773528161,"version":"4.6.1"},"reference-count":35,"publisher":"National Academy of Sciences","issue":"33","license":[{"start":{"date-parts":[[2023,8,7]],"date-time":"2023-08-07T00:00:00Z","timestamp":1691366400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["BT\/PR38173\/MED\/97\/474\/2020"],"award-info":[{"award-number":["BT\/PR38173\/MED\/97\/474\/2020"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,8,15]]},"abstract":"\n Microbes evolve rapidly by modifying their genomes through mutations or through the horizontal acquisition of mobile genetic elements (MGEs) linked with fitness traits such as antimicrobial resistance (AMR), virulence, and metabolic functions. We conducted a multicentric study in India and collected different clinical samples for decoding the genome sequences of bacterial pathogens associated with sepsis, urinary tract infections, and respiratory infections to understand the functional potency associated with AMR and its dynamics. Genomic analysis identified several acquired AMR genes (ARGs) that have a pathogen-specific signature. We observed that\n \n bla\n CTX-M-15<\/jats:sub>\n <\/jats:italic>\n ,\n \n bla\n CMY-42<\/jats:sub>\n <\/jats:italic>\n ,\n bla<\/jats:italic>\n NDM-5<\/jats:sub>\n , and\n aadA<\/jats:italic>\n (2) were prevalent in\n Escherichia coli<\/jats:italic>\n , and\n bla<\/jats:italic>\n TEM-1B<\/jats:sub>\n ,\n bla<\/jats:italic>\n OXA-232<\/jats:sub>\n ,\n bla<\/jats:italic>\n NDM-1<\/jats:sub>\n ,\n rmtB<\/jats:italic>\n , and\n rmtC<\/jats:italic>\n were dominant in\n Klebsiella pneumoniae<\/jats:italic>\n . In contrast,\n Pseudomonas aeruginosa<\/jats:italic>\n and\n Acinetobacter baumannii<\/jats:italic>\n harbored\n \n bla\n VEB<\/jats:sub>\n <\/jats:italic>\n ,\n \n bla\n VIM-2<\/jats:sub>\n <\/jats:italic>\n ,\n aph(<\/jats:italic>\n 3\u2019),\n strA\/B<\/jats:italic>\n ,\n \n bla\n OXA-23<\/jats:sub>\n <\/jats:italic>\n ,\n aph<\/jats:italic>\n (3\u2032) variants, and\n amrA<\/jats:italic>\n , respectively. Regardless of the type of ARG, the MGEs linked with ARGs were also pathogen-specific. The sequence type of these pathogens was identified as high-risk international clones, with only a few lineages being predominant and region-specific. Whole-cell proteome analysis of extensively drug-resistant\n K. pneumoniae<\/jats:italic>\n ,\n A. baumannii, E. coli,<\/jats:italic>\n and\n P. aeruginosa<\/jats:italic>\n strains revealed differential abundances of resistance-associated proteins in the presence and absence of different classes of antibiotics. The pathogen-specific resistance signatures and differential abundance of AMR-associated proteins identified in this study should add value to AMR diagnostics and the choice of appropriate drug combinations for successful antimicrobial therapy.\n <\/jats:p>","DOI":"10.1073\/pnas.2305465120","type":"journal-article","created":{"date-parts":[[2023,8,7]],"date-time":"2023-08-07T15:11:27Z","timestamp":1691421087000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":46,"title":["Antimicrobial resistance heterogeneity among multidrug-resistant Gram-negative pathogens: Phenotypic, genotypic, and proteomic analysis"],"prefix":"10.1073","volume":"120","author":[{"given":"Tanshi","family":"Mehrotra","sequence":"first","affiliation":[{"name":"Infection and Immunology Division, Functional Genomics Laboratory, Centre for Microbial Research, Translational Health Science and Technology Institute, Faridabad 121001, 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India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradipta","family":"Jana","sequence":"additional","affiliation":[{"name":"Infection and Immunology Division, Functional Genomics Laboratory, Centre for Microbial Research, Translational Health Science and Technology Institute, Faridabad 121001, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prabhakar","family":"Babele","sequence":"additional","affiliation":[{"name":"Infection and Immunology Division, Functional Genomics Laboratory, Centre for Microbial Research, Translational Health Science and Technology Institute, Faridabad 121001, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepjyoti","family":"Paul","sequence":"additional","affiliation":[{"name":"Infection and Immunology Division, Functional Genomics Laboratory, Centre for Microbial Research, Translational Health Science and Technology Institute, Faridabad 121001, 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Jeeva","family":"Sankar","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, All India Institute of Medical Sciences, New Delhi 110029, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishnamohan","family":"Atmakuri","sequence":"additional","affiliation":[{"name":"Infection and Immunology Division, Functional Genomics Laboratory, Centre for Microbial Research, Translational Health Science and Technology Institute, Faridabad 121001, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramesh","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, All India Institute of Medical Sciences, New Delhi 110029, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajni","family":"Gaind","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi 110029, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mamatha","family":"Ballal","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal 576104, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nagamani","family":"Kammili","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Pathogen Biology Division, Gandhi Medical College and Hospital, Secunderabad 500003, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rupak K.","family":"Bhadra","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Immunology Division, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology, Kolkata 700 032, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thandavarayan","family":"Ramamurthy","sequence":"additional","affiliation":[{"name":"Infection and Immunology Division, Functional Genomics Laboratory, Centre for Microbial Research, Translational Health Science and Technology Institute, Faridabad 121001, India"},{"name":"Division of Bacteriology, Indian Council of Medical Research-National Institute of Cholera and Enteric Diseases, Kolkata 700010, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. 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