The Staphylococcus aureus Response to Unsaturated Long Chain Free Fatty Acids: Survival Mechanisms and Virulence Implications
Open Access
- 2 February 2009
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 4 (2), e4344
- https://doi.org/10.1371/journal.pone.0004344
Abstract
Staphylococcus aureus is an important human commensal and opportunistic pathogen responsible for a wide range of infections. Long chain unsaturated free fatty acids represent a barrier to colonisation and infection by S. aureus and act as an antimicrobial component of the innate immune system where they are found on epithelial surfaces and in abscesses. Despite many contradictory reports, the precise anti-staphylococcal mode of action of free fatty acids remains undetermined. In this study, transcriptional (microarrays and qRT-PCR) and translational (proteomics) analyses were applied to ascertain the response of S. aureus to a range of free fatty acids. An increase in expression of the σB and CtsR stress response regulons was observed. This included increased expression of genes associated with staphyloxanthin synthesis, which has been linked to membrane stabilisation. Similarly, up-regulation of genes involved in capsule formation was recorded as were significant changes in the expression of genes associated with peptidoglycan synthesis and regulation. Overall, alterations were recorded predominantly in pathways involved in cellular energetics. In addition, sensitivity to linoleic acid of a range of defined (sigB, arcA, sasF, sarA, agr, crtM) and transposon-derived mutants (vraE, SAR2632) was determined. Taken together, these data indicate a common mode of action for long chain unsaturated fatty acids that involves disruption of the cell membrane, leading to interference with energy production within the bacterial cell. Contrary to data reported for other strains, the clinically important EMRSA-16 strain MRSA252 used in this study showed an increase in expression of the important virulence regulator RNAIII following all of the treatment conditions tested. An adaptive response by S. aureus of reducing cell surface hydrophobicity was also observed. Two fatty acid sensitive mutants created during this study were also shown to diplay altered pathogenesis as assessed by a murine arthritis model. Differences in the prevalence and clinical importance of S. aureus strains might partly be explained by their responses to antimicrobial fatty acids.Keywords
This publication has 108 references indexed in Scilit:
- Mode of action of human β-defensin 3 against Staphylococcus aureus and transcriptional analysis of responses to defensin challengeInternational Journal of Medical Microbiology, 2008
- Mutated Response Regulator graR Is Responsible for Phenotypic Conversion of Staphylococcus aureus from Heterogeneous Vancomycin-Intermediate Resistance to Vancomycin-Intermediate ResistanceAntimicrobial Agents and Chemotherapy, 2008
- Characterization of Monolaurin Resistance in Enterococcus faecalisApplied and Environmental Microbiology, 2007
- The cidA murein hydrolase regulator contributes to DNA release and biofilm development in Staphylococcus aureusProceedings of the National Academy of Sciences of the United States of America, 2007
- SarA Is a Repressor of hla (α-Hemolysin) Transcription in Staphylococcus aureus : Its Apparent Role as an Activator of hla in the Prototype Strain NCTC 8325 Depends on Reduced Expression of sarSJournal of Bacteriology, 2006
- Reporter Metabolite Analysis of Transcriptional Profiles of a Staphylococcus aureus Strain with Normal Phenotype and Its Isogenic hemB Mutant Displaying the Small-Colony-Variant PhenotypeJournal of Bacteriology, 2006
- Staphyloxanthin Plays a Role in the Fitness of Staphylococcus aureus and Its Ability To Cope with Oxidative StressInfection and Immunity, 2006
- Contributions of sigB and sarA to distinct multiple antimicrobial resistance mechanisms of Staphylococcus aureusInternational Journal of Antimicrobial Agents, 2006
- Metabolic Fate and Selective Utilization of Major Fatty Acids in Human Sebaceous GlandJournal of Investigative Dermatology, 2002
- Improved staining of proteins in polyacrylamide gels including isoelectric focusing gels with clear background at nanogram sensitivity using Coomassie Brilliant Blue G‐250 and R‐250Electrophoresis, 1988