{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T23:20:04Z","timestamp":1789600804152,"version":"build-2803163510"},"reference-count":42,"publisher":"Microbiology Society","issue":"9","license":[{"start":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T00:00:00Z","timestamp":1725408000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"crossref","award":["FT180100123"],"award-info":[{"award-number":["FT180100123"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,9,4]]},"abstract":"<jats:p>\n                  <jats:italic>Klebsiella pneumoniae<\/jats:italic> is a pathogen of major concern in the global rise of antimicrobial resistance and has been implicated as a reservoir for the transfer of resistance genes between species. The upregulation of efflux pumps is a particularly concerning mechanism of resistance acquisition as, in many instances, a single point mutation can simultaneously provide resistance to a range of antimicrobials and biocides. The current study investigated mutations in <jats:italic>oqxR<\/jats:italic>, which encodes a negative regulator of the RND-family efflux pump genes, <jats:italic>oqxAB<\/jats:italic>, natively found in the chromosome of <jats:italic>K. pneumoniae<\/jats:italic>. Resistant mutants in four <jats:italic>K. pneumoniae<\/jats:italic> strains (KP6870155, NTUH-K2044, SGH10, and ATCC43816) were selected from single exposures to 30 \u00b5g\/mL chloramphenicol and 12 mutants were selected for whole genome sequencing to identify mutations associated with resistance. Resistant mutants generated by single exposures to chloramphenicol, tetracycline, or ciprofloxacin at \u22654 X MIC were replica plated onto all three antibiotics to observe simultaneous cross-resistance to all compounds, indicative of a multidrug resistance phenotype. A variety of novel mutations, including single point mutations, deletions, and insertions, were found to disrupt <jats:italic>oqxR<\/jats:italic> leading to significant and simultaneous increases in resistance to chloramphenicol, tetracycline, and ciprofloxacin. The <jats:italic>oqxAB<\/jats:italic>-<jats:italic>oqxR<\/jats:italic> locus has been mobilized and dispersed on plasmids in many Enterobacteriaceae species and the diversity of these loci was examined to evaluate the evolutionary pressures acting on these genes. Comparison of the promoter regions of <jats:italic>oqxR<\/jats:italic> in plasmid-borne copies of the <jats:italic>oqxR-oqxAB<\/jats:italic> operon indicated that some constructs may produce truncated versions of the <jats:italic>oqxR<\/jats:italic> transcript, which may impact on <jats:italic>oqxAB<\/jats:italic> regulation and expression. In some instances, co-carriage of chromosomal and plasmid encoded <jats:italic>oqxAB-oqxR<\/jats:italic> was found in <jats:italic>K. pneumoniae<\/jats:italic>, implying that there is selective pressure to maintain and expand the efflux pump. Given that OqxR is a repressor of <jats:italic>oqxAB<\/jats:italic>, any mutation affecting its expression or function can lead to multidrug resistance. This is in contrast to antibiotic target site mutations that must occur in limited sequence space to be effective and not impact the fitness of the cell. Therefore, <jats:italic>oqxR<\/jats:italic> may act as a simple genetic switch to facilitate resistance via OqxAB mediated efflux.<\/jats:p>","DOI":"10.1099\/mic.0.001499","type":"journal-article","created":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T13:18:12Z","timestamp":1725455892000},"source":"Crossref","is-referenced-by-count":6,"title":["Mutations in the efflux regulator gene oqxR provide a simple genetic switch for antimicrobial resistance in Klebsiella pneumoniae"],"prefix":"10.1099","volume":"170","author":[{"given":"Catherine J.","family":"Dawson","sequence":"first","affiliation":[{"name":"University of Newcastle, Newcastle, Australia"},{"name":"ARC Centre of Excellence in Synthetic Biology, Macquarie University, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelia","family":"Bartczak","sequence":"additional","affiliation":[{"name":"ARC Centre of Excellence in Synthetic Biology, Macquarie University, Sydney, Australia"},{"name":"University of Newcastle, Newcastle, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2031-9679","authenticated-orcid":false,"given":"Karl A.","family":"Hassan","sequence":"additional","affiliation":[{"name":"ARC Centre of Excellence in Synthetic Biology, Macquarie University, Sydney, Australia"},{"name":"University of Newcastle, Newcastle, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"345","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)02724-0"},{"key":"R2","article-title":"Antimicrobial resistance surveillance in Europe 2022 - 2020 data. 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