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Phasevarions mediate epigenetic regulation of antimicrobial susceptibility in Neisseria meningitidis

Antimicrob Agents Chemother. 2014 Jul;58(7):4219-21. doi: 10.1128/AAC.00004-14. Epub 2014 Apr 28.

Abstract

Phase variation is a common feature of host-adapted bacterial pathogens such as Neisseria meningitidis. Recently, we reported that this rapid on/off switching of gene expression occurs in DNA methyltransferases, altering expression in multiple genes via changes in global methylation. In the current study, we compared MIC values of strains with ModA11, ModA12, and ModD1 phasevarions, revealing MIC differences due to ModA11 and ModA12 switching, with a ModA11_OFF strain showing 4-fold reduced susceptibilities to ceftazidime and ciprofloxacin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Ceftazidime / pharmacology
  • Ciprofloxacin / pharmacology
  • DNA (Cytosine-5-)-Methyltransferases / genetics*
  • DNA Methylation / genetics
  • DNA, Bacterial / genetics
  • Drug Resistance, Multiple, Bacterial / genetics*
  • Epigenesis, Genetic
  • Gene Expression Regulation, Bacterial / genetics
  • Microbial Sensitivity Tests
  • Neisseria meningitidis / drug effects*
  • Neisseria meningitidis / genetics*
  • Neisseria meningitidis / metabolism

Substances

  • Anti-Bacterial Agents
  • DNA, Bacterial
  • Ciprofloxacin
  • Ceftazidime
  • DNA (Cytosine-5-)-Methyltransferases