Bacillithiol: a key protective thiol in Staphylococcus aureus

Expert Rev Anti Infect Ther. 2015;13(9):1089-107. doi: 10.1586/14787210.2015.1064309. Epub 2015 Jul 16.

Abstract

Bacillithiol is a low-molecular-weight thiol analogous to glutathione and is found in several Firmicutes, including Staphylococcus aureus. Since its discovery in 2009, bacillithiol has been a topic of interest because it has been found to contribute to resistance during oxidative stress and detoxification of electrophiles, such as the antibiotic fosfomycin, in S. aureus. The rapid increase in resistance of methicillin-resistant Staphylococcus aureus (MRSA) to available therapeutic agents is a great health concern, and many research efforts are focused on identifying new drugs and targets to combat this organism. This review describes the discovery of bacillithiol, studies that have elucidated the physiological roles of this molecule in S. aureus and other Bacilli, and the contribution of bacillithiol to S. aureus fitness during pathogenesis. Additionally, the bacillithiol biosynthesis pathway is evaluated as a novel drug target that can be utilized in combination with existing therapies to treat S. aureus infections.

Keywords: Staphylococcus aureus; bacillithiol; bacillithiol conjugate amidase; drug resistance; fosfomycin; oxidative stress; pathogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use
  • Cysteine / analogs & derivatives*
  • Cysteine / chemistry
  • Cysteine / pharmacology
  • Cysteine / therapeutic use
  • Glucosamine / analogs & derivatives*
  • Glucosamine / chemistry
  • Glucosamine / pharmacology
  • Glucosamine / therapeutic use
  • Humans
  • Methicillin-Resistant Staphylococcus aureus / drug effects
  • Methicillin-Resistant Staphylococcus aureus / physiology
  • Phylogeny
  • Staphylococcal Infections / diagnosis
  • Staphylococcal Infections / drug therapy
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / physiology
  • Sulfhydryl Compounds / chemistry
  • Sulfhydryl Compounds / pharmacology
  • Sulfhydryl Compounds / therapeutic use

Substances

  • Anti-Bacterial Agents
  • Sulfhydryl Compounds
  • bacillithiol
  • Cysteine
  • Glucosamine