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Published on: June 1, 2010

Spontaneous pmrA mutants of Salmonella typhimurium LT2 define a new two-component regulatory system with a possible

K L Roland1, L E Martin, C R Esther

  • 1Department of Microbiology and Immunology, Emory University, Atlanta, Georgia 30322.

Journal of Bacteriology
|July 1, 1993
PubMed

Insights

Spontaneous mutations in Salmonella typhimurium increased resistance to neutrophil antibacterial proteins and polymyxin B. The pmrA mutation identified a novel two-component regulatory system, PmrA-PmrB, crucial for bacterial defense.

Area of Science:

  • Microbiology
  • Bacterial genetics
  • Antimicrobial resistance

Background:

  • Salmonella typhimurium possesses resistance mechanisms against host defense peptides.
  • Cationic antibacterial proteins and polymyxin B are critical components of the innate immune system.

Purpose of the Study:

  • To identify and characterize spontaneous mutations in Salmonella typhimurium conferring resistance to cationic antibacterial proteins and polymyxin B.
  • To elucidate the genetic basis of this increased resistance.

Main Methods:

  • Isolation and mapping of spontaneous mutations in Salmonella typhimurium LT2.
  • Cloning and DNA sequencing of the mutated genes.
  • Comparative sequence analysis to identify genetic alterations.

Main Results:

  • A mutation, pmrA505, was identified, conferring a 1,000-fold increase in polymyxin B resistance and 2- to 4-fold increase in resistance to neutrophil proteins.
  • DNA sequencing revealed three open reading frames (ORFs); ORF2 and ORF3 showed homology to the OmpR-EnvZ two-component regulatory system.
  • The pmrA505 mutation was localized to ORF2, designated PmrA, involving a single G-A transition.
  • ORF3 was designated PmrB, a histidine kinase-sensor protein.

Conclusions:

  • A novel two-component regulatory system, PmrA-PmrB, is involved in Salmonella typhimurium resistance to antimicrobial peptides.
  • The PmrA-PmrB system represents a potential target for antimicrobial drug development.

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