{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T03:50:23Z","timestamp":1793764223623,"version":"4.6.1"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Biomed Sci"],"published-print":{"date-parts":[[2010,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>The cationic peptide antibiotic polymyxin has recently been reevaluated in the treatment of severe infections caused by gram negative bacteria.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>In this study, the genetic determinants for capsular polysaccharide level and lipopolysaccharide modification involved in polymyxin B resistance of the opportunistic pathogen <jats:italic>Klebsiella pneumoniae<\/jats:italic> were characterized. The expressional control of the genes responsible for the resistance was assessed by a LacZ reporter system. The PmrD connector-mediated regulation for the expression of <jats:italic>pmr<\/jats:italic> genes involved in polymyxin B resistance was also demonstrated by DNA EMSA, two-hybrid analysis and <jats:italic>in vitro<\/jats:italic> phosphor-transfer assay.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Deletion of the <jats:italic>rcsB<\/jats:italic>, which encoded an activator for the production of capsular polysaccharide, had a minor effect on <jats:italic>K. pneumoniae<\/jats:italic> resistance to polymyxin B. On the other hand, deletion of <jats:italic>ugd<\/jats:italic> or <jats:italic>pmrF<\/jats:italic> gene resulted in a drastic reduction of the resistance. The polymyxin B resistance was shown to be regulated by the two-component response regulators PhoP and PmrA at low magnesium and high iron, respectively. Similar to the control identified in <jats:italic>Salmonella<\/jats:italic>, expression of <jats:italic>pmrD<\/jats:italic> in <jats:italic>K. pneumoniae<\/jats:italic> was dependent on PhoP, the activated PmrD would then bind to PmrA to prolong the phosphorylation state of the PmrA, and eventually turn on the expression of <jats:italic>pmr<\/jats:italic> for the resistance to polymyxin B.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>The study reports a role of the capsular polysaccharide level and the <jats:italic>pmr<\/jats:italic> genes for <jats:italic>K. pneumoniae<\/jats:italic> resistance to polymyxin B. The PmrD connector-mediated pathway in governing the regulation of <jats:italic>pmr<\/jats:italic> expression was demonstrated. In comparison to the <jats:italic>pmr<\/jats:italic> regulation in <jats:italic>Salmonella<\/jats:italic>, PhoP in <jats:italic>K. pneumoniae<\/jats:italic> plays a major regulatory role in polymyxin B resistance.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1423-0127-17-60","type":"journal-article","created":{"date-parts":[[2010,7,24]],"date-time":"2010-07-24T18:13:44Z","timestamp":1279995224000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":153,"title":["Molecular characterization of the PhoPQ-PmrD-PmrAB mediated pathway regulating polymyxin B resistance in Klebsiella pneumoniae CG43"],"prefix":"10.1186","volume":"17","author":[{"given":"Hsin-Yao","family":"Cheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Fong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hwei-Ling","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2010,7,24]]},"reference":[{"key":"174_CR1","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1128\/CMR.11.4.589","volume":"11","author":"R Podschun","year":"1998","unstructured":"Podschun R, Ullmann U: Klebsiella spp. as nosocomial pathogens: epidemiology, taxonomy, typing methods, and pathogenicity factors. 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