{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T06:58:52Z","timestamp":1778828332811,"version":"3.51.4"},"reference-count":70,"publisher":"Microbiology Society","issue":"12","license":[{"start":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T00:00:00Z","timestamp":1766102400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical Research Council","award":["MR\/V009885\/1"],"award-info":[{"award-number":["MR\/V009885\/1"]}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"crossref","award":["BB\/X01651X"],"award-info":[{"award-number":["BB\/X01651X"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,19]]},"abstract":"<jats:p>\n                    <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                    is a prominent opportunistic pathogen increasingly associated with multidrug resistance and virulence. One of the main mechanisms of antimicrobial resistance in\n                    <jats:italic>K. pneumoniae<\/jats:italic>\n                    is active efflux, primarily mediated by the resistance-nodulation-division (RND) family of pumps. AcrAB-TolC is the key RND efflux pump in\n                    <jats:italic>K. pneumoniae<\/jats:italic>\n                    , regulated by the transcriptional activator RamA and its repressor RamR. Although overexpression of AcrAB-TolC has been linked to drug resistance in various clinical strains, its physiological roles in\n                    <jats:italic>K. pneumoniae<\/jats:italic>\n                    remain insufficiently studied. In this study, we generated isogenic deletions of\n                    <jats:italic>acrB<\/jats:italic>\n                    and\n                    <jats:italic>ramR<\/jats:italic>\n                    in both the genetically tractable\n                    <jats:italic>K. pneumoniae<\/jats:italic>\n                    Ecl8 and the virulent ATCC 43816 strains. We examined the phenotype of the \u0394\n                    <jats:italic>acrB<\/jats:italic>\n                    and \u0394\n                    <jats:italic>ramR<\/jats:italic>\n                    mutants by assessing antimicrobial susceptibility, biofilm formation, growth under infection-related conditions and both\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    infection models. Loss of\n                    <jats:italic>acrB<\/jats:italic>\n                    increased susceptibility to drugs, decreased biofilm formation and reduced\n                    <jats:italic>in vitro<\/jats:italic>\n                    virulence in both Ecl8 and ATCC 43816. However, only in Ecl8 was the loss of AcrB found to diminish growth under infection-like conditions and decrease\n                    <jats:italic>in vivo<\/jats:italic>\n                    virulence in the\n                    <jats:italic>Galleria mellonella<\/jats:italic>\n                    infection model. In contrast, in ATCC 43816, it had no effect. Our findings suggest that AcrAB-TolC exhibits strain-specific physiological functions, highlighting its dual role in antimicrobial resistance and pathogenicity, and thereby broadening our understanding of efflux-mediated adaptations in\n                    <jats:italic>K. pneumoniae<\/jats:italic>\n                    . Exploring the broader functions of RND efflux pumps in\n                    <jats:italic>K. pneumoniae<\/jats:italic>\n                    can provide insights into the potential effects of targeting them with inhibitor molecules.\n                  <\/jats:p>","DOI":"10.1099\/mic.0.001647","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T12:17:22Z","timestamp":1766146642000},"source":"Crossref","is-referenced-by-count":1,"title":["Strain-dependent contribution of the AcrAB-TolC efflux pump to Klebsiella pneumoniae physiology"],"prefix":"10.1099","volume":"171","author":[{"given":"Kirandeep","family":"Bhogal","sequence":"first","affiliation":[{"name":"Department of Microbes, Infection and Microbiomes, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham, UK"},{"name":"Institute of Microbiology and Infection, University of Birmingham, Birmingham, 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xmlns:xhtml=\"http:\/\/www.w3.org\/1999\/xhtml\" xml:lang=\"en\"&gt;&lt;p&gt;This article is part of our &lt;span style=\"color: rgb(33, 51, 104);\"&gt;&lt;a href=\"\/content\/emerging-investigators-collection-2025-26\"&gt;Emerging Investigators collection&lt;\/a&gt;&lt;\/span&gt;.&lt;\/p&gt;&lt;p style=\"line-height: 1.2;\"&gt;&lt;img src=\"\/upload\/emerging\/ilyas_alav.png\" alt=\"photo of Ilyas Alav\" class=\"ImageBorder img-responsive eb-people fr-fic fr-dib\" style=\"width: 120px; float: left; margin: 0 10px 10px 0;\" \/&gt;&lt;span style=\"font-size: 12px; font-weight: normal;\"&gt;&lt;strong&gt;Ilyas Alav&lt;\/strong&gt; obtained his PhD in microbiology and infection from the University of Birmingham, where he researched RND efflux pump-mediated antibiotic resistance in Salmonella Typhimurium. As a postdoctoral fellow, he investigated plasmid transmission inhibitors in Enterobacterales and their mechanisms of action to limit the spread of antimicrobial resistance genes. Subsequently, he became a teaching fellow, during which time his research interest in multidrug efflux pumps rekindled, leading him to apply for funding to establish his own research team. He is currently a Wellcome Trust Fellow at the Sir William Dunn School of Pathology, University of Oxford. Currently, trainees within his team are investigating the molecular mechanisms of multidrug efflux pumps in bacterial virulence, using &lt;em&gt;Salmonella Typhimurium&lt;\/em&gt; as a model pathogen. His research aims to develop anti-virulence strategies by targeting efflux pumps to combat bacterial infections. Alongside his research, he is enthusiastic about teaching and supervising students and early-career researchers to support their professional development.&amp;#160;&lt;\/span&gt;&lt;\/p&gt;\n&lt;\/xhtml:span&gt;"],"short-title":[],"issued":{"date-parts":[[2025,12,19]]},"references-count":70,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12,19]]}},"URL":"https:\/\/doi.org\/10.1099\/mic.0.001647","relation":{},"ISSN":["1350-0872","1465-2080"],"issn-type":[{"value":"1350-0872","type":"print"},{"value":"1465-2080","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,19]]}}}