Dataset Information

Analysis of cell wall and cytoplasmic proteomes of a vancomcyin intermediate resistant Staphylococcus aureus strain (HIP5827) and its derivatives (VP32 and P100)

ABSTRACT: Not available

INSTRUMENT(S): instrument model

ORGANISM(S): Staphylococcus Aureus

SUBMITTER: Attila Csordas

PROVIDER: PRD000503 | Pride | 2012-07-26

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	PRIDE_Exp_Complete_Ac_18209.pride.mgf.gz	Mgf
	PRIDE_Exp_Complete_Ac_18209.pride.mztab.gz	Mztab
	PRIDE_Exp_Complete_Ac_18209.xml.gz	Xml
	PRIDE_Exp_Complete_Ac_18210.pride.mgf.gz	Mgf
	PRIDE_Exp_Complete_Ac_18210.pride.mztab.gz	Mztab

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Publications

Proteomic profiling of cell envelope-associated proteins from Staphylococcus aureus.

Gatlin Christine L CL Pieper Rembert R Huang Shih-Ting ST Mongodin Emmanuel E Gebregeorgis Elizabeth E Parmar Prashanth P PP Clark David J DJ Alami Hamid H Papazisi Leka L Fleischmann Robert D RD Gill Steven R SR Peterson Scott N SN

Proteomics 20060301 5

The emergence of highly virulent community acquired Staphylococcus aureus and continued progression of resistance to multiple antimicrobials, including methicillin and vancomycin, marks the reemergence of S. aureus as a serious health care threat. Investigation of proteins localized to the cell surface could help to elucidate mechanisms of virulence and antibiotic resistance in S. aureus. In this study, proteomic profiling methods were developed to solubilize, display, and evaluate abundance lev ...[more]

PMID: 16470658

Similar Datasets

Project description:Resistance to antibiotics is an increasing problem and necessitates novel antibacterial therapies. The polyketide antibiotics cervimycin A to D are natural products of Streptomyces tendae HKI 0179 with promising activity against multidrug-resistant staphylococci and vancomycin-resistant enterococci. To initiate mode of action studies, we selected cervimycin C- and D-resistant (CmR) Staphylococcus aureus strains. Genome sequencing of CmR mutants revealed amino acid exchanges in the essential histidine kinase WalK, the Clp protease proteolytic subunit ClpP or the Clp ATPase ClpC, and the heat shock protein DnaK. Interestingly, all characterized CmR mutants harbored a combination of mutations in walK and clpP or clpC. In vitro and in vivo analyses showed that the mutations in the Clp proteins abolished ClpP or ClpC activity, and the deletion of clpP rendered S. aureus but not all Bacillus subtilis strains cervimycin-resistant. The essential gene walK was the second mutational hotspot in the CmR S. aureus strains, which decreased WalK activity in vitro and generated a vancomycin-intermediate resistant phenotype, with a thickened cell wall, a lower growth rate, and reduced cell lysis. Transcriptomic and proteomic analyses revealed massive alterations in the CmR strains compared to the parent strain S. aureus SG511, with major shifts in the heat shock regulon, the metal ion homeostasis, and the carbohydrate metabolism. Taken together, mutations in the heat shock genes clpP, clpC, and dnaK, and the walK kinase gene in CmR mutants induced a vancomycin-intermediate resistant phenotype in S. aureus, suggesting cell wall metabolism or the Clp protease system as primary target of cervimycin. IMPORTANCE Staphylococcus aureus is a frequent cause of infections in both the community and hospital setting. Resistance development of S. aureus to various antibiotics is a severe problem for the treatment of this pathogen worldwide. New powerful antimicrobial agents against Gram-positives are needed, since antibiotics like vancomycin fail to cure vancomycin-intermediate resistant S. aureus (VISA) and vancomycin-resistant enterococci (VRE) infections. One candidate substance with promising activity against these organisms is cervimycin, which is an antibiotic complex with a yet unknown mode of action. In our study, we provide first insights into the mode of action of cervimycins. By characterizing cervimycin-resistant S. aureus strains, we revealed the Clp system and the essential kinase WalK as mutational hotspots for cervimycin resistance in S. aureus. It further emerged that cervimycin-resistant S. aureus strains show a VISA phenotype, indicating a role of cervimycin in perturbing the bacterial cell envelope.