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Regulation of polymyxin resistance and adaptation to low-Mg2+ environments

E A Groisman1, J Kayser, F C Soncini

  • 1Howard Hughes Medical Institute and Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA. groisman@borcim.wustl.edu

Journal of Bacteriology
|November 26, 1997
PubMed

Insights

Salmonella typhimurium

Area of Science:

  • Microbiology
  • Bacterial Pathogenesis
  • Molecular Biology

Background:

  • The PmrA-PmrB two-component system in Salmonella typhimurium regulates resistance to polymyxin B and neutrophil antimicrobial proteins.
  • Modifications to lipopolysaccharide (LPS) by PmrA reduce negative charge, enhancing bacterial survival against cationic antimicrobial peptides.
  • These LPS modifications are linked to bacterial adaptation in low magnesium (Mg2+) environments.

Purpose of the Study:

  • To identify PmrA-activated genes essential for polymyxin resistance in Salmonella typhimurium.
  • To investigate the role of LPS modifications in bacterial adaptation to low Mg2+ and acidic conditions.
  • To understand how Salmonella typhimurium evades host antimicrobial defenses.

Main Methods:

  • Genetic analysis to identify PmrA-activated loci required for polymyxin resistance.
  • Phenotypic characterization of bacterial growth and survival under varying Mg2+ concentrations and pH.
  • Assessment of bacterial resistance to polymyxin B and host antimicrobial proteins.

Main Results:

  • Three PmrA-activated loci were identified as crucial for polymyxin resistance.
  • LPS modifications conferring polymyxin resistance are also vital for growth in low Mg2+ conditions.
  • Growth in mildly acidic pH and low Mg2+ concentrations significantly enhances polymyxin resistance in wild-type Salmonella.
  • These conditions promote PmrA-activated gene expression, increasing resistance to host antimicrobial proteins.

Conclusions:

  • The PmrA-PmrB system orchestrates LPS modifications for polymyxin resistance and Mg2+ homeostasis.
  • Salmonella typhimurium utilizes LPS as a Mg2+ reservoir, modifying its surface charge to survive in nutrient-limited and hostile environments.
  • These findings highlight a key mechanism for bacterial evasion of host immune responses.

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