Molecular characterization of the PhoPQ-PmrD-PmrAB mediated pathway regulating polymyxin B resistance in <it>Klebsiella pneumoniae </it>CG43
<p>Abstract</p> <p>Background</p> <p>The cationic peptide antibiotic polymyxin has recently been reevaluated in the treatment of severe infections caused by gram negative bacteria.</p> <p>Methods</p> <p>In this study, the genetic determinants for...
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| Format: | Article |
| Language: | English |
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BMC
2010-07-01
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| Series: | Journal of Biomedical Science |
| Online Access: | http://www.jbiomedsci.com/content/17/1/60 |
| _version_ | 1819044025736364032 |
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| author | Peng Hwei-Ling Chen Yi-Fong Cheng Hsin-Yao |
| author_facet | Peng Hwei-Ling Chen Yi-Fong Cheng Hsin-Yao |
| author_sort | Peng Hwei-Ling |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>The cationic peptide antibiotic polymyxin has recently been reevaluated in the treatment of severe infections caused by gram negative bacteria.</p> <p>Methods</p> <p>In this study, the genetic determinants for capsular polysaccharide level and lipopolysaccharide modification involved in polymyxin B resistance of the opportunistic pathogen <it>Klebsiella pneumoniae </it>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 <it>pmr </it>genes involved in polymyxin B resistance was also demonstrated by DNA EMSA, two-hybrid analysis and <it>in vitro </it>phosphor-transfer assay.</p> <p>Results</p> <p>Deletion of the <it>rcsB</it>, which encoded an activator for the production of capsular polysaccharide, had a minor effect on <it>K. pneumoniae </it>resistance to polymyxin B. On the other hand, deletion of <it>ugd </it>or <it>pmrF </it>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 <it>Salmonella</it>, expression of <it>pmrD </it>in <it>K. pneumoniae </it>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 <it>pmr </it>for the resistance to polymyxin B.</p> <p>Conclusions</p> <p>The study reports a role of the capsular polysaccharide level and the <it>pmr </it>genes for <it>K. pneumoniae </it>resistance to polymyxin B. The PmrD connector-mediated pathway in governing the regulation of <it>pmr </it>expression was demonstrated. In comparison to the <it>pmr </it>regulation in <it>Salmonella</it>, PhoP in <it>K. pneumoniae </it>plays a major regulatory role in polymyxin B resistance.</p> |
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| issn | 1021-7770 1423-0127 |
| language | English |
| last_indexed | 2024-12-21T10:06:07Z |
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| spelling | doaj.art-b22d8e2cdfbe418e8e3bb937b55f1aa32022-12-21T19:07:50ZengBMCJournal of Biomedical Science1021-77701423-01272010-07-011716010.1186/1423-0127-17-60Molecular characterization of the PhoPQ-PmrD-PmrAB mediated pathway regulating polymyxin B resistance in <it>Klebsiella pneumoniae </it>CG43Peng Hwei-LingChen Yi-FongCheng Hsin-Yao<p>Abstract</p> <p>Background</p> <p>The cationic peptide antibiotic polymyxin has recently been reevaluated in the treatment of severe infections caused by gram negative bacteria.</p> <p>Methods</p> <p>In this study, the genetic determinants for capsular polysaccharide level and lipopolysaccharide modification involved in polymyxin B resistance of the opportunistic pathogen <it>Klebsiella pneumoniae </it>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 <it>pmr </it>genes involved in polymyxin B resistance was also demonstrated by DNA EMSA, two-hybrid analysis and <it>in vitro </it>phosphor-transfer assay.</p> <p>Results</p> <p>Deletion of the <it>rcsB</it>, which encoded an activator for the production of capsular polysaccharide, had a minor effect on <it>K. pneumoniae </it>resistance to polymyxin B. On the other hand, deletion of <it>ugd </it>or <it>pmrF </it>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 <it>Salmonella</it>, expression of <it>pmrD </it>in <it>K. pneumoniae </it>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 <it>pmr </it>for the resistance to polymyxin B.</p> <p>Conclusions</p> <p>The study reports a role of the capsular polysaccharide level and the <it>pmr </it>genes for <it>K. pneumoniae </it>resistance to polymyxin B. The PmrD connector-mediated pathway in governing the regulation of <it>pmr </it>expression was demonstrated. In comparison to the <it>pmr </it>regulation in <it>Salmonella</it>, PhoP in <it>K. pneumoniae </it>plays a major regulatory role in polymyxin B resistance.</p>http://www.jbiomedsci.com/content/17/1/60 |
| spellingShingle | Peng Hwei-Ling Chen Yi-Fong Cheng Hsin-Yao Molecular characterization of the PhoPQ-PmrD-PmrAB mediated pathway regulating polymyxin B resistance in <it>Klebsiella pneumoniae </it>CG43 Journal of Biomedical Science |
| title | Molecular characterization of the PhoPQ-PmrD-PmrAB mediated pathway regulating polymyxin B resistance in <it>Klebsiella pneumoniae </it>CG43 |
| title_full | Molecular characterization of the PhoPQ-PmrD-PmrAB mediated pathway regulating polymyxin B resistance in <it>Klebsiella pneumoniae </it>CG43 |
| title_fullStr | Molecular characterization of the PhoPQ-PmrD-PmrAB mediated pathway regulating polymyxin B resistance in <it>Klebsiella pneumoniae </it>CG43 |
| title_full_unstemmed | Molecular characterization of the PhoPQ-PmrD-PmrAB mediated pathway regulating polymyxin B resistance in <it>Klebsiella pneumoniae </it>CG43 |
| title_short | Molecular characterization of the PhoPQ-PmrD-PmrAB mediated pathway regulating polymyxin B resistance in <it>Klebsiella pneumoniae </it>CG43 |
| title_sort | molecular characterization of the phopq pmrd pmrab mediated pathway regulating polymyxin b resistance in it klebsiella pneumoniae it cg43 |
| url | http://www.jbiomedsci.com/content/17/1/60 |
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