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Coinfections are common in cats, but no coinfection studies have investigated the\n              <jats:italic>in vitro<\/jats:italic>\n              dynamics between feline viral and bacterial pathogens. In this study, we performed co-culture and invasion assays to investigate the ability of common feline bacterial respiratory pathogens,\n              <jats:italic>Chlamydia felis<\/jats:italic>\n              and\n              <jats:italic>Mycoplasma felis<\/jats:italic>\n              , to replicate in and invade into Crandell\u2013Rees feline kidney cells. We subsequently investigated how coinfection of these feline cells with each bacterium (\n              <jats:italic>C. felis<\/jats:italic>\n              or\n              <jats:italic>M. felis<\/jats:italic>\n              ) and the common feline viral pathogen, felid alphaherpesvirus 1 (FHV-1), affects replication of each agent in this cell culture system. We also investigated the metabolic impact of each co-pathogen using metabolomic analysis of infected and coinfected cells.\n              <jats:italic>C. felis<\/jats:italic>\n              was able to invade and replicate in CRFKs, while\n              <jats:italic>M. felis<\/jats:italic>\n              had little capacity to invade. During coinfection, FHV-1 replication was minimally affected by the presence of either bacterial pathogen, but bacterial replication kinetics were more affected, particularly in\n              <jats:italic>M. felis<\/jats:italic>\n              . Both\n              <jats:italic>C. felis<\/jats:italic>\n              and\n              <jats:italic>M. felis<\/jats:italic>\n              replicated to higher levels in the presence of a secondary pathogen. Coinfections resulted in reprogramming of the glycolysis pathway, the pentose phosphate pathway, and the tricarboxylic acid cycle. The distinct metabolic profiles of coinfected cells compared to those of cells infected with just one of these three pathogens, as well as the impact of coinfections on viral or bacterial load, suggest strong interactions between these three pathogens and possible synergistic mechanisms enhancing virulence that need further investigation.\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>In the natural world, respiratory pathogens coexist within their hosts, but their dynamics and interactions remain largely unexplored. Herpesviruses, mycoplasmas, and chlamydias are common and significant causes of acute and chronic respiratory and system disease in animals and people, and these diseases are increasingly found to be polymicrobial. This study investigates how coinfection of feline cells between three respiratory pathogens of cats impact each other as well as the host innate metabolic response to infection. Each of these pathogens have been implicated in the induction of feline upper respiratory tract disease in cats, which is the leading cause of euthanasia in shelters. Understanding how coinfection impacts co-pathogenesis and host responses is critical for improving disease management.<\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/msystems.00852-24","type":"journal-article","created":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T13:04:51Z","timestamp":1727183091000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":4,"title":["A \u201cplus one\u201d strategy impacts replication of felid alphaherpesvirus 1,\n            <i>Mycoplasma<\/i>\n            and\n            <i>Chlamydia,<\/i>\n            and the metabolism of coinfected feline cells"],"prefix":"10.1128","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3565-6400","authenticated-orcid":true,"given":"Sara M.","family":"Klose","sequence":"first","affiliation":[{"name":"Asia-Pacific Centre for Animal Health, Melbourne Veterinary School, University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7225-2632","authenticated-orcid":false,"given":"David P.","family":"De Souza","sequence":"additional","affiliation":[{"name":"Metabolomics Australia, Bio21 Institute, University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0400-9670","authenticated-orcid":false,"given":"Joanne M.","family":"Devlin","sequence":"additional","affiliation":[{"name":"Asia-Pacific Centre for Animal Health, Melbourne Veterinary School, University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1159-7394","authenticated-orcid":true,"given":"Rhys","family":"Bushell","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinical Sciences, Melbourne Veterinary School, University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0903-2469","authenticated-orcid":true,"given":"Glenn F.","family":"Browning","sequence":"additional","affiliation":[{"name":"Asia-Pacific Centre for Animal Health, Melbourne Veterinary School, University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6877-7383","authenticated-orcid":true,"given":"Paola K.","family":"Vaz","sequence":"additional","affiliation":[{"name":"Asia-Pacific Centre for Animal Health, Melbourne Veterinary School, University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1177\/1098612X16634387"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cvsm.2011.07.006"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1177\/1098612X18813248"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/jsap.13623"},{"key":"e_1_3_4_6_2","first-page":"181","article-title":"Prevalence of feline herpesvirus-1, feline calicivirus, Chlamydia felis, and Bordetella bronchiseptica in a population of shelter cats on Prince Edward Island","volume":"84","author":"Walter J","year":"2020","unstructured":"Walter J, Foley P, Yason C, Vanderstichel R, Muckle A. 2020. 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