Bacitracin sensing in Bacillus subtilis

Mol Microbiol. 2008 May;68(3):768-85. doi: 10.1111/j.1365-2958.2008.06194.x.

Abstract

The extracellular presence of antibiotics is a common threat in microbial life. Their sensitive detection and subsequent induction of appropriate resistance mechanisms is therefore a prerequisite for survival. The bacitracin stress response network of Bacillus subtilis consists of four signal-transducing systems, the two-component systems (TCS) BceRS, YvcPQ and LiaRS, and the extracytoplasmic function (ECF) sigma factor sigma(M). Here, we investigated the mechanism of bacitracin perception and the response hierarchy within this network. The BceRS-BceAB TCS/ABC transporter module is the most sensitive and efficient bacitracin resistance determinant. The ABC transporter BceAB not only acts as a bacitracin detoxification pump, but is also crucial for bacitracin sensing, indicative of a novel mechanism of stimulus perception, conserved in Firmicutes bacteria. The Bce system seems to respond to bacitracin directly (drug sensing), whereas the LiaRS TCS and sigma(M) respond only at higher concentrations and indirectly to bacitracin action (damage sensing). The YvcPQ-YvcRS system is subject to cross-activation via the paralogous Bce system, and is therefore only indirectly induced by bacitracin. The bacitracin stress response network is optimized to respond to antibiotic gradients in a way that maximizes the gain and minimizes the costs of this stress response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / chemistry
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism*
  • Adenosine Triphosphate / metabolism
  • Anti-Bacterial Agents / metabolism
  • Anti-Bacterial Agents / pharmacology*
  • Bacillus subtilis / drug effects*
  • Bacillus subtilis / genetics
  • Bacitracin / analogs & derivatives
  • Bacitracin / metabolism
  • Bacitracin / pharmacology*
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Biological Transport / drug effects
  • Drug Resistance, Bacterial
  • Gene Expression Regulation, Bacterial
  • Genes, Reporter
  • Genetic Complementation Test
  • Hydrolysis
  • Promoter Regions, Genetic
  • Protein Structure, Tertiary
  • Sequence Deletion
  • Signal Transduction / drug effects

Substances

  • ATP-Binding Cassette Transporters
  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Bacitracin
  • Adenosine Triphosphate