Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

S. aureus gene expression following growth in media containing oleic acid

ABSTRACT: S. aureus response to exogenous fatty acid (oleic acid) Gene expression profiles were generated by microarray analysis of S. aureus cells grown in media without or with oleic aicd Comparison of expression profiles after growth of S. aureus in exogenous fatty acid S. aureus was grown in media with and without oleic acid to an OD600nm of 0.5, and RNA was extracted to look at the gobal gene expression.

ORGANISM(S): Staphylococcus aureus subsp. aureus RN4220

SUBMITTER: Matthew Frank

PROVIDER: E-GEOD-36231 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Membrane disruption by antimicrobial fatty acids releases low-molecular-weight proteins from Staphylococcus aureus.

Parsons Joshua B JB Yao Jiangwei J Frank Matthew W MW Jackson Pamela P Rock Charles O CO

Journal of bacteriology 20120727 19

The skin represents an important barrier for pathogens and is known to produce fatty acids that are toxic toward gram-positive bacteria. A screen of fatty acids as growth inhibitors of Staphylococcus aureus revealed structure-specific antibacterial activity. Fatty acids like oleate (18:1Δ9) were nontoxic, whereas palmitoleate (16:1Δ9) was a potent growth inhibitor. Cells treated with 16:1Δ9 exhibited rapid membrane depolarization, the disruption of all major branches of macromolecular synthesis, ...[more]

PMID: 22843840

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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

S. aureus gene expression following growth in media containing oleic acid

Publications

Membrane disruption by antimicrobial fatty acids releases low-molecular-weight proteins from Staphylococcus aureus.

Similar Datasets

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