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Distinct virulent network between healthcare- and community-associated Staphylococcus aureus based on proteomic analysis.

ABSTRACT: 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.

SUBMITTER: He L

PROVIDER: S-EPMC5757299 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Distinct virulent network between healthcare- and community-associated <i>Staphylococcus aureus</i> based on proteomic analysis.

He Lei L Meng Hongwei H Liu Qian Q Hu Mo M Wang Yanan Y Chen Xiaoying X Liu Xiaoyun X Li Min M

Clinical proteomics 20180108

<h4>Background</h4><i>Staphylococcus aureus</i> (<i>S. aureus</i> 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, <i>etc</i>. 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 ...[more]

PMID: 29321722

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Project description:Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) USA300 has spread rapidly across North America, and CA-MRSA is also increasing in Australia. However, the dominant Australian CA-MRSA strain, ST93-IV [2B] appears distantly related to USA300 despite strikingly similar clinical and epidemiological profiles. Here, we compared the virulence of a recent Australian ST93 isolate (JKD6159) to other MRSA, including USA300, and found that JKD6159 was the most virulent in a mouse skin infection model. We fully sequenced the genome of JKD6159 and confirmed that JKD6159 is a distinct clone with 7616 single nucleotide polymorphisms (SNPs) distinguishing this strain from all other S. aureus genomes. Despite its high virulence there were surprisingly few virulence determinants. However, genes encoding ?-hemolysin, Panton-Valentine leukocidin (PVL) and ?-type phenol soluble modulins were present. Genome comparisons revealed 32 additional CDS in JKD6159 but none appeared to encode new virulence factors, suggesting that this clone's enhanced pathogenicity could lie within subtler genome changes, such as SNPs within regulatory genes. To investigate the role of accessory genome elements in CA-MRSA epidemiology, we next sequenced three additional Australian non-ST93 CA-MRSA strains and compared them with JKD6159, 19 completed S. aureus genomes and 59 additional S. aureus genomes for which unassembled genome sequence data was publicly available (82 genomes in total). These comparisons showed that despite its distinctive genotype, JKD6159 and other CA-MRSA clones (including USA300) share a conserved repertoire of three notable accessory elements (SSCmecIV, PVL prophage, and pMW2). This study demonstrates that the genetically distinct ST93 CA-MRSA from Australia is highly virulent. Our comparisons of geographically and genetically diverse CA-MRSA genomes suggest that apparent convergent evolution in CA-MRSA may be better explained by the rapid dissemination of a highly conserved accessory genome from a common source.

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Project description:Sequence type (ST) 59 is an epidemic lineage of community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA) isolates. Taiwanese CA-MRSA isolates belong to ST59 and can be grouped into 2 distinct clones, a virulent Taiwan clone and a commensal Asian-Pacific clone. The Taiwan clone carries the Panton-Valentine leukocidin (PVL) genes and the staphylococcal chromosomal cassette mec (SCCmec) VT, and is frequently isolated from patients with severe disease. The Asian-Pacific clone is PVL-negative, carries SCCmec IV, and a frequent colonizer of healthy children. Isolates of both clones were characterized by their ability to adhere to respiratory A549 cells, cytotoxicity to human neutrophils, and nasal colonization of a murine and murine sepsis models. Genome variation was determined by polymerase chain reaction of selected virulence factors and by multi-strain whole genome microarray. Additionally, the expression of selected factors was compared between the 2 clones. The Taiwan clone showed a much higher cytotoxicity to the human neutrophils and caused more severe septic infections with a high mortality rate in the murine model. The clones were indistinguishable in their adhesion to A549 cells and persistence of murine nasal colonization. The microarray data revealed that the Taiwan clone had lost the ø3-prophage that integrates into the ?-hemolysin gene and includes staphylokinase- and enterotoxin P-encoding genes, but had retained the genes for human immune evasion, scn and chps. Production of the virulence factors did not differ significantly in the 2 clonal groups, although more ?-toxin was expressed in Taiwan clone isolates from pneumonia patients. In conclusion, the Taiwan CA-MRSA clone was distinguished by enhanced virulence in both humans and an animal infection model. The evolutionary acquisition of PVL, the higher expression of ?-toxin, and possibly the loss of a large portion of the ?-hemolysin-converting prophage likely contribute to its higher pathogenic potential than the Asian-Pacific clone.

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Distinct virulent network between healthcare- and community-associated Staphylococcus aureus based on proteomic analysis.

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Distinct virulent network between healthcare- and community-associated <i>Staphylococcus aureus</i> based on proteomic analysis.

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