Dataset Information

Joint Genomic and Proteomic Analysis Identifies Meta-Trait Characteristics of Virulent and Non-virulent Staphylococcus aureus Strains.

ABSTRACT: Staphylococcus aureus is an opportunistic pathogen of humans and warm-blooded animals and presents a growing threat in terms of multi-drug resistance. Despite numerous studies, the basis of staphylococcal virulence and switching between commensal and pathogenic phenotypes is not fully understood. Using genomics, we show here that S. aureus strains exhibiting virulent (VIR) and non-virulent (NVIR) phenotypes in a chicken embryo infection model genetically fall into two separate groups, with the VIR group being much more cohesive than the NVIR group. Significantly, the genes encoding known staphylococcal virulence factors, such as clumping factors, are either found in different allelic variants in the genomes of NVIR strains (compared to VIR strains) or are inactive pseudogenes. Moreover, the pyruvate carboxylase and gamma-aminobutyrate permease genes, which were previously linked with virulence, are pseudogenized in NVIR strain ch22. Further, we use comprehensive proteomics tools to characterize strains that show opposing phenotypes in a chicken embryo virulence model. VIR strain CH21 had an elevated level of diapolycopene oxygenase involved in staphyloxanthin production (protection against free radicals) and expressed a higher level of immunoglobulin-binding protein Sbi on its surface compared to NVIR strain ch22. Furthermore, joint genomic and proteomic approaches linked the elevated production of superoxide dismutase and DNA-binding protein by NVIR strain ch22 with gene duplications.

SUBMITTER: Bonar EA

PROVIDER: S-EPMC6136393 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Joint Genomic and Proteomic Analysis Identifies Meta-Trait Characteristics of Virulent and Non-virulent Staphylococcus aureus Strains.

Bonar Emilia A EA Bukowski Michal M Hydzik Marcin M Jankowska Urszula U Kedracka-Krok Sylwia S Groborz Magdalena M Dubin Grzegorz G Akkerboom Viktoria V Miedzobrodzki Jacek J Sabat Artur J AJ Friedrich Alexander W AW Wladyka Benedykt B

Frontiers in cellular and infection microbiology 20180906

Staphylococcus aureus is an opportunistic pathogen of humans and warm-blooded animals and presents a growing threat in terms of multi-drug resistance. Despite numerous studies, the basis of staphylococcal virulence and switching between commensal and pathogenic phenotypes is not fully understood. Using genomics, we show here that S. aureus strains exhibiting virulent (VIR) and non-virulent (NVIR) phenotypes in a chicken embryo infection model genetically fall into two separate grou ...[more]

PMID: 30237986

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Project description:Background:Staphylococcus aureus (S. aureus or SA) is a leading cause of healthcare-associated (HA-) and community-associated (CA) infection. HA-SA isolates usually cause nosocomial pneumonia, bloodstream infections, catheter-related urinary tract infections, etc. On the other hand, CA-SA isolates usually cause highly fatal diseases, such as SSTIs as well as post influenza necrotic hemorrhagic pneumonia. The differences of the infection types are partially due to the unique characteristics between HA-SA and CA-SA isolates. For example, HA-SA isolates showed strong adherence to host epithelial cells, while CA-SA isolates displayed higher virulence due to the increased activity of the important quorum-sensing system accessory gene regulator (agr). Thus, the aim of this study was to characterize the proteomic difference between HA-SA and CA-SA lineage. Methods:In this study, the extracted peptides from those representative strains were analyzed by LC-MS/MS. The protein-protein interaction network was constructed by bioinformatics and their expressions were verified by RT-PCR and Western blot. Results:We demonstrated that Agr system (AgrA and AgrC) and its interactive factors (PhoP, SrrB, YycG, SarX, SigB and ClpP) based on the protein-protein interaction network were expressed significantly higher in the epidemic Chinese CA-SA lineage ST398 compared to HA-SA lineage ST239 by LC-MS/MS. We further verified the increased transcription of all these genes in ST398 by RT-PCR, suggesting that the higher expression of these genes/proteins probably play role in the acute infection of CA-SA. Moreover, surface-related proteins (FnbpA, SpA, Atl, ClfA, IsaA, IsaB, LtaS, SsaA and Cna) that are repressed by the Agr system have significantly higher expression in the epidemic Chinese HA-SA clone ST239 in comparison to CA-SA lineage ST398 by LC-MS/MS. Furthermore, we confirmed the significantly increased expression of two important adhesive proteins (Atl and ClfA) in ST239 by Western blot, which may contribute to the durative infection of HA-SA. Conclusion:The results suggest that the different proteomic profile, at least partially, contribute to the pathogenic differences between HA-SA and CA-SA.

Project description:BackgroundThe delta-toxin (δ-toxin) of Staphylococcus aureus is the only hemolysin shown to cause mast cell degranulation and is linked to atopic dermatitis, a chronic inflammatory skin disease. We sought to characterize variation in δ-toxin production across S. aureus strains and identify genetic loci potentially associated with differences between strains.MethodsA set of 124 S. aureus strains was genome-sequenced and δ-toxin levels in stationary phase supernatants determined by high performance liquid chromatography (HPLC). SNPs and kmers were associated with differences in toxin production using four genome-wide association study (GWAS) methods. Transposon mutations in candidate genes were tested for their δ-toxin levels. We constructed XGBoost models to predict toxin production based on genetic loci discovered to be potentially associated with the phenotype.ResultsThe S. aureus strain set encompassed 40 sequence types (STs) in 23 clonal complexes (CCs). δ-toxin production ranged from barely detectable levels to >90,000 units, with a median of >8,000 units. CC30 had significantly lower levels of toxin production than average while CC45 and CC121 were higher. MSSA (methicillin sensitive) strains had higher δ-toxin production than MRSA (methicillin resistant) strains. Through multiple GWAS approaches, 45 genes were found to be potentially associated with toxicity. Machine learning models using loci discovered through GWAS as features were able to predict δ-toxin production (as a high/low binary phenotype) with a precision of .875 and specificity of .990 but recall of .333. We discovered that mutants in the carA gene, encoding the small chain of carbamoyl phosphate synthase, completely abolished toxin production and toxicity in Caenorhabditis elegans.ConclusionsThe amount of stationary phase production of the toxin is a strain-specific phenotype likely affected by a complex interaction of number of genes with different levels of effect. We discovered new candidate genes that potentially play a role in modulating production. We report for the first time that the product of the carA gene is necessary for δ-toxin production in USA300. This work lays a foundation for future work on understanding toxin regulation in S. aureus and prediction of phenotypes from genomic sequences.

Dataset Information

Joint Genomic and Proteomic Analysis Identifies Meta-Trait Characteristics of Virulent and Non-virulent Staphylococcus aureus Strains.

Publications

Joint Genomic and Proteomic Analysis Identifies Meta-Trait Characteristics of Virulent and Non-virulent <i>Staphylococcus aureus</i> Strains.

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