Dataset Information

S-nitrosylated cysteine residues identification in Staphylococcus aureus XN108

ABSTRACT: Staphylococcus aureus is a major human pathogen that causes diverse severe infections. The emergence of multi-drug resistance has caused S. aureus infection a global concern, especially resistance to vancomycin, a drug of last resort. A growing body of research focuses on the resistance mechanisms and antibiotic discovery. S-nitrosylation, a posttranslational modification on cysteine thiol mediated by Nitric oxide (NO) has been found to drive a large part of the ubiquitous influence of NO on mediating cellular functions. Several gram-positive microorganisms, including S. aureus, possess a bacterial NO synthase (bNOS) to generate NO endogenously. bNOS was reported to play an important role in protecting bacteria against a wide spectrum of antibiotics, but the precise underlying mechanism remains elusive. Here, S-nitrosylation patterns were analyzed in a clinically isolated vancomycin-intermediate staphylococcus aureus strain XN108 by liquid chromatography-mass spectrometry (LC-MS)/MS. The MS data of samples XN_1 and XN_2 were integrated and analyzed.

ORGANISM(S): Staphylococcus Aureus

SUBMITTER: Baolin Sun

PROVIDER: PXD041143 | iProX | Mon Mar 27 00:00:00 BST 2023

REPOSITORIES: iProX

ACCESS DATA

Publications

Transcription tuned by S-nitrosylation underlies a mechanism for Staphylococcus aureus to circumvent vancomycin killing.

Shu Xueqin X Shi Yingying Y Huang Yi Y Yu Dan D Sun Baolin B

Nature communications 20230421 1

Treatment of Staphylococcus aureus infections is a constant challenge due to emerging resistance to vancomycin, a last-resort drug. S-nitrosylation, the covalent attachment of a nitric oxide (NO) group to a cysteine thiol, mediates redox-based signaling for eukaryotic cellular functions. However, its role in bacteria is largely unknown. Here, proteomic analysis revealed that S-nitrosylation is a prominent growth feature of vancomycin-intermediate S. aureus. Deletion of NO synthase (NOS) or remov ...[more]

PMID: 37085493

Similar Datasets

Project description:The GntR-like protein NorG has been shown to affect Staphylococcus aureus genes involved in the resistance to quinolones and beta-lactams such as those encoding the NorB and AbcA transporters. To identify the target genes regulated by NorG, we carried out transcriptional profiling assays using S. aureus RN6390 and its isogenic norG::cat mutant. Our data showed that NorG positively affected the transcription of global regulators mgrA, arlS, and sarZ. The three putative drug efflux pump genes most positively affected by NorG were the NorB efflux pump (5.1-fold), the MmpL-like protein SACOL2566 (5.2-fold), and the BcrA-like drug transporter SACOL2525 (5.7-fold). The S. aureus predicted MmpL protein showed 53% homology with the MmpL lipid transporter of Mycobacterium tuberculosis, and the putative SACOL2525 protein showed 87% homology with the bacitracin drug transporter BcrA of Staphylococcus hominis. Two pump genes most negatively affected by NorG were NorC (4-fold) and AbcA (6-fold). Other categories of genes such as those participating in amino acid, inorganic ion, or nucleotide transporters and metabolism, were also affected by NorG. Real-time RT-PCR assays for mgrA, arlS, sarZ, norB, norC, abcA, mmpL, and bcrA-like were carried out to verify microarray data and showed the same level of up- or down regulation by NorG. The norG mutant showed a twofold increase in the resistance to norfloxacin and rhodamine, both substrates of the NorC transporter, which is consistent with the resistance phenotype conferred by overexpression of norC on a plasmid. These data indicate that NorG has broad regulatory function in S. aureus. The goal of this study was to define the transcriptional response of S. aureus norG mutant cells. To do so, commercially available S. aureus Affymetrix GeneChips (Santa Clara, CA) were used to compare the expression properties of wild type (ISP794) and isogenic norG (QT11) mutant cells. S. aureus strains ISP794 and QT11 were grown to mid exponential phase growth, lysed , total bacterial RNA was extracted, labeled and hybridized to commerically available S. aureus Affymetrix GeneChips. In total three biological replicates were compared for each strain background.

Project description:Heinemann2005 - Genome-scale reconstruction of Staphylococcus aureus (iMH551) This model is described in the article: In silico genome-scale reconstruction and validation of the Staphylococcus aureus metabolic network. Heinemann M, Kümmel A, Ruinatscha R, Panke S. Biotechnol. Bioeng. 2005 Dec; 92(7): 850-864 Abstract: A genome-scale metabolic model of the Gram-positive, facultative anaerobic opportunistic pathogen Staphylococcus aureus N315 was constructed based on current genomic data, literature, and physiological information. The model comprises 774 metabolic processes representing approximately 23% of all protein-coding regions. The model was extensively validated against experimental observations and it correctly predicted main physiological properties of the wild-type strain, such as aerobic and anaerobic respiration and fermentation. Due to the frequent involvement of S. aureus in hospital-acquired bacterial infections combined with its increasing antibiotic resistance, we also investigated the clinically relevant phenotype of small colony variants and found that the model predictions agreed with recent findings of proteome analyses. This indicates that the model is useful in assisting future experiments to elucidate the interrelationship of bacterial metabolism and resistance. To help directing future studies for novel chemotherapeutic targets, we conducted a large-scale in silico gene deletion study that identified 158 essential intracellular reactions. A more detailed analysis showed that the biosynthesis of glycans and lipids is rather rigid with respect to circumventing gene deletions, which should make these areas particularly interesting for antibiotic development. The combination of this stoichiometric model with transcriptomic and proteomic data should allow a new quality in the analysis of clinically relevant organisms and a more rationalized system-level search for novel drug targets. This model is hosted on BioModels Database and identified by: MODEL1507180072. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Dataset Information

S-nitrosylated cysteine residues identification in Staphylococcus aureus XN108

Publications

Transcription tuned by S-nitrosylation underlies a mechanism for Staphylococcus aureus to circumvent vancomycin killing.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets