Haem toxicity provides a competitive advantage to the clinically relevant Staphylococcus aureus small colony variant phenotype

Microbiology (Reading). 2021 Apr;167(4):001044. doi: 10.1099/mic.0.001044.

Abstract

Microorganisms encounter toxicities inside the host. Many pathogens exist as subpopulations to maximize survivability. Subpopulations of Staphylococcus aureus include antibiotic-tolerant small colony variants (SCVs). These mutants often emerge following antibiotic treatment but can be present in infections prior to antibiotic exposure. We hypothesize that haem toxicity in the host selects for respiration-deficient S. aureus SCVs in the absence of antibiotics. We demonstrate that some but not all respiration-deficient SCV phenotypes are more protective than the haem detoxification system against transient haem exposure, indicating that haem toxicity in the host may contribute to the dominance of menaquinone-deficient and haem-deficient SCVs prior to antibiotic treatment.

Keywords: SCV; Small colony variants; Staphylococcus aureus; antibiotic tolerance; haem toxicity; respiration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Heme / metabolism*
  • Heme / toxicity
  • Humans
  • Phenotype
  • Staphylococcal Infections / metabolism*
  • Staphylococcal Infections / microbiology*
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / genetics
  • Staphylococcus aureus / growth & development*
  • Staphylococcus aureus / metabolism*
  • Vitamin K 2 / metabolism

Substances

  • Anti-Bacterial Agents
  • Vitamin K 2
  • Heme