Dataset Information

Staphylococcus aureus membrane vesicles confer resistance to antimicrobial fatty acids

ABSTRACT: S. aureus is a common commensal inhabitant of skin and nares of healthy individuals. In these environments, S. aureus overcomes colonisation barriers deployed by the innate immune system, which include long chain unsaturated free fatty acids with known potent anti-staphylococcal activity. S. aureus resistance mechanisms to these antimicrobial fatty acids (AFAs) remain elusive. However, it is well-documented that AFAs target S. aureus membrane, and increase its fluidity. This is associated with a drastic change in secreted proteins. The most abundantly secreted proteins in response to AFAs were recently identified to be components of S. aureus membrane vesicles (MVs), as revealed by proteomics analyses. Here, we demonstrate that MVs are decoys that trap AFAs. Importantly, MV release and composition are modulated by AFAs to promote bacterial survival.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Staphylococcus Aureus

SUBMITTER: Nicolas Nalpas

LAB HEAD: Prof. Dr. Andreas Peschel

PROVIDER: PXD018809 | Pride | 2021-09-09

REPOSITORIES: Pride

ACCESS DATA

Publications

Staphylococcus aureus Releases Proinflammatory Membrane Vesicles To Resist Antimicrobial Fatty Acids.

Kengmo Tchoupa Arnaud A Peschel Andreas A

mSphere 20200930 5

Staphylococcus aureus is a major pathogen, which colonizes one in three otherwise healthy humans. This significant spread of S. aureus is largely due to its ability to circumvent innate immune responses, including antimicrobial fatty acids (AFAs) on the skin and in nasal secretions. In response to AFAs, S. aureus swiftly induces resistance mechanisms, which have yet to be completely elucidated. Here, we identify membrane vesicle (MV) release as a resistance strategy used by ...[more]

PMID: 32999082

Similar Datasets

Project description:Subinhibitory concentrations of the neuroleptic drug thioridazine (TDZ) are well-known to enhance the killing of methicillin-resistant S. aureus (MRSA) by Î²-lactam antibiotics, however, the mechanism underlying the synergy between TDZ and Î²-lactams is not fully understood. In the present study we have examined the effect of a subinhibitory concentration of TDZ on antimicrobial resistance, the global transcriptome, and the cell wall composition of MRSA USA300. We show that TDZ is able to sensitize the bacteria to several classes of antimicrobials targeting the late stages of peptidoglycan synthesis. Furthermore, our microarray analysis demonstrates that TDZ modulates the expression of genes encoding membrane and surface proteins, transporters, and enzymes involved in amino acid biosynthesis. Interestingly, resemblance between the transcriptional profile of TDZ treatment and the transcriptomic response of S. aureus to known inhibitors of cell wall synthesis suggests that TDZ disturbs peptidoglycan biosynthesis at a stage that precedes transpeptidation. In support of this notion, dramatic changes in the muropeptide profile of USA300 were observed following growth in the presence of TDZ, indicating that TDZ can interfere with the formation of the pentaglycine branches. Strikingly, the addition of glycine to the growth medium relieved the effect of TDZ on the muropeptide profile. Furthermore, exogenous glycine offered a modest protective effect against TDZ-induced Î²-lactam sensitivity. We propose that TDZ exposure leads to a shortage of intracellular amino acids, including glycine, which is required for the production of normal peptidoglycan precursors with pentaglycine branches, the correct substrate of S. aureus penicillin-binding proteins. Collectively, this work demonstrates that TDZ has a major impact on the cell wall biosynthesis pathway in S. aureus and provides new insights into how MRSA may be sensitized towards Î²-lactam antibiotics. Staphylococcus aureus USA300 was grown to early exponential phase and treated with TDZ (16 Âµg/ml) alone or in combination with DCX (0.125 Âµg/ml) for 30 min. Changes in global gene expression were analyzed using the untreated culture as control. Hybridizations were performed in triplicate using RNA isolated from independent cultures.

Dataset Information

Staphylococcus aureus membrane vesicles confer resistance to antimicrobial fatty acids

Publications

Staphylococcus aureus Releases Proinflammatory Membrane Vesicles To Resist Antimicrobial Fatty Acids.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure