- 作者: Hsin-Yao Cheng; Yi-Fong Chen; Hwei-Ling Peng
- 作者服務機構: Department of Biological Science and Technology, National Chiao-Tung University, Hsin Chu, Taiwan, Republic of China
- 中文摘要: --
- 英文摘要:
Background: The cationic peptide antibiotic polymyxin has recently been reevaluated in the
treatment of severe infections caused by gram negative bacteria.
Methods: In this study, the genetic determinants for capsular polysaccharide level and
lipopolysaccharide modification involved in polymyxin B resistance of the
opportunistic pathogen Klebsiella pneumoniae 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 pmr genes
involved in polymyxin B resistance was also demonstrated by DNA EMSA, twohybrid
analysis and in vitro phosphor-transfer assay.
Results: Deletion of the rcsB, which encoded an activator for the production of capsular
polysaccharide, had a minor effect on K. pneumoniae resistance to polymyxin B. On
the other hand, deletion of ugd or pmrF gene resulted in a drastic reduction of the
resistance. The polymyxin B resistance was shown to be regulated by the twocomponent
response regulators PhoP and PmrA at low magnesium and high iron,
respectively. Similar to the control identified in Salmonella, expression of pmrD in K.
pneumoniae 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 pmr for the resistance to polymyxin B.
Conclusions: The study reports a role of the capsular polysaccharide level and the pmr genes for K.
pneumoniae resistance to polymyxin B. The PmrD connector-mediated pathway in
governing the regulation of pmr expression was demonstrated. In comparison to the pmr regulation in Salmonella, PhoP in K. pneumoniae plays a major regulatory role in
polymyxin B resistance. - 中文關鍵字: --
- 英文關鍵字: --