The ABC-Type Efflux Pump MacAB Protects Salmonella enterica serovar Typhimurium from Oxidative Stress
Open Access
- 31 December 2013
- journal article
- Published by American Society for Microbiology in mBio
- Vol. 4 (6), e00630-13
- https://doi.org/10.1128/mbio.00630-13
Abstract
Multidrug efflux pumps are integral membrane proteins known to actively excrete antibiotics. The macrolide-specific pump MacAB, the only ABC-type drug efflux pump in Salmonella, has previously been linked to virulence in mice. The molecular mechanism of this link between macAB and infection is unclear. We demonstrate that macAB plays a role in the detoxification of reactive oxygen species (ROS), compounds that salmonellae are exposed to at various stages of infection. macAB is induced upon exposure to H2O2 and is critical for survival of Salmonella enterica serovar Typhimurium in the presence of peroxide. Furthermore, we determined that macAB is required for intracellular replication inside J774.A1 murine macrophages but is not required for survival in ROS-deficient J774.D9 macrophages. macAB mutants also had reduced survival in the intestine in the mouse colitis model, a model characterized by a strong neutrophilic intestinal infiltrate where bacteria may experience the cytotoxic actions of ROS. Using an Amplex red-coupled assay, macAB mutants appear to be unable to induce protection against exogenous H2O2 in vitro, in contrast to the isogenic wild type. In mixed cultures, the presence of the wild-type organism, or media preconditioned by the growth of the wild-type organism, was sufficient to rescue the macAB mutant from peroxide-mediated killing. Our data indicate that the MacAB drug efflux pump has functions beyond resistance to antibiotics and plays a role in the protection of Salmonella against oxidative stress. Intriguingly, our data also suggest the presence of a soluble anti-H2O2 compound secreted by Salmonella cells through a MacAB-dependent mechanism.This publication has 95 references indexed in Scilit:
- Effect of Transcriptional Activators SoxS, RobA, and RamA on Expression of Multidrug Efflux Pump AcrAB-TolC in Enterobacter cloacaeAntimicrobial Agents and Chemotherapy, 2012
- Enteric Commensal Bacteria Induce Extracellular Signal-regulated Kinase Pathway Signaling via Formyl Peptide Receptor-dependent Redox Modulation of Dual Specific Phosphatase 3Journal of Biological Chemistry, 2011
- Nitric Oxide Protects Bacteria from Aminoglycosides by Blocking the Energy-Dependent Phases of Drug UptakeAntimicrobial Agents and Chemotherapy, 2011
- Oxidative Stress Induction of the MexXY Multidrug Efflux Genes and Promotion of Aminoglycoside Resistance Development in Pseudomonas aeruginosaAntimicrobial Agents and Chemotherapy, 2011
- The SoxRS response of Escherichia coli is directly activated by redox‐cycling drugs rather than by superoxideMolecular Microbiology, 2011
- Correlation of the expression of acrB and the regulatory genes marA, soxS and ramA with antimicrobial resistance in clinical isolates of Klebsiella pneumoniae endemic to New York CityJournal of Antimicrobial Chemotherapy, 2009
- The Pseudomonas aeruginosa multidrug efflux regulator MexR uses an oxidation-sensing mechanismProceedings of the National Academy of Sciences of the United States of America, 2008
- AcrAB Multidrug Efflux Pump Regulation in Salmonella enterica serovar Typhimurium by RamA in Response to Environmental SignalsOnline Journal of Public Health Informatics, 2008
- During infection of epithelial cells Salmonella enterica serovar Typhimurium undergoes a time-dependent transcriptional adaptation that results in simultaneous expression of three type 3 secretion systemsCellular Microbiology, 2008
- Antimicrobial reactive oxygen and nitrogen species: concepts and controversiesNature Reviews Microbiology, 2004