Comparative proteomics profiling reveals down-regulation of Staphylococcus aureus virulence in achieving intermediate vancomycin resistance

Xin Ee Tan, Hui Min Neoh, Mee Lee Looi, Toh Leong Tan, Salasawati Hussin, Longzhu Cui, Keiichi Hiramatsu, A. Rahman A. Jamal

Research output: Contribution to journalArticle

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Abstract

Aims: VraSR and GraSR were shown to be important in conferring intermediate vancomycin resistance in VISA. Nevertheless, the exact mechanism modulated by these systems leading to the development of VISA remains unclear. We employed a proteomic approach to determine the VraS and GraR regulons and subsequently derive the possible vancomycin resistance regulatory pathway(s) in the Mu50 lineage of Staphylococcus aureus. Methodology and results: Staphylococcus aureus strains Mu50Ω, Mu50Ω-vraSm and Mu50Ω-vraSm-graRm are isogenic strains with ascending levels of vancomycin resistance. Total proteins were extracted from the 3 strains and trypsin digested prior to protein isolation and identification by LC-ESI MS/MS and PLGS 2.4. Expression profiles of resulting proteins were analyzed using Progenesis LC/MS software. Differential expression profiles revealed 3 regulons, each controlled by VraS (Mu50Ω-vraSm vs Mu50Ω), GraR (Mu50Ω-vraSm-graRm vs Mu50Ω-vraSm) and VraS-GraR (Mu50Ω-vraSm-graRm vs Mu50Ω), respectively. The regulon down-regulated by VraS in Mu50Ω-vraSm were proteins associated with virulence (MgrA, Rot, and SarA), while GraR up-regulated resistance-associated proteins (TpiA, ArcB and IsaA) in Mu50Ω-vraSm-graRm. The VraS-GraR regulon mediated both up-regulation of resistance-associated proteins (ArgF, ArcB, VraR and SerS) and down-regulation of virulence-associated protein GapB. Conclusion, significance and impact of study: Down-regulation of virulence- in concert with up-regulation of resistance-associated proteins appears to be integral for development of intermediate-vancomycin resistance in the Mu50 lineage of S. aureus.

Original languageEnglish
Pages (from-to)498-505
Number of pages8
JournalMalaysian Journal of Microbiology
Volume12
Issue number6
Publication statusPublished - 2016

Fingerprint

Vancomycin Resistance
Proteomics
Virulence
Staphylococcus aureus
Down-Regulation
Regulon
Proteins
Up-Regulation
Trypsin
Software

Keywords

  • Proteomics profiling
  • Staphylococcus aureus
  • Vancomycin-intermediate
  • Virulence

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

Comparative proteomics profiling reveals down-regulation of Staphylococcus aureus virulence in achieving intermediate vancomycin resistance. / Tan, Xin Ee; Neoh, Hui Min; Looi, Mee Lee; Tan, Toh Leong; Hussin, Salasawati; Cui, Longzhu; Hiramatsu, Keiichi; A. Jamal, A. Rahman.

In: Malaysian Journal of Microbiology, Vol. 12, No. 6, 2016, p. 498-505.

Research output: Contribution to journalArticle

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AU - Tan, Xin Ee

AU - Neoh, Hui Min

AU - Looi, Mee Lee

AU - Tan, Toh Leong

AU - Hussin, Salasawati

AU - Cui, Longzhu

AU - Hiramatsu, Keiichi

AU - A. Jamal, A. Rahman

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AB - Aims: VraSR and GraSR were shown to be important in conferring intermediate vancomycin resistance in VISA. Nevertheless, the exact mechanism modulated by these systems leading to the development of VISA remains unclear. We employed a proteomic approach to determine the VraS and GraR regulons and subsequently derive the possible vancomycin resistance regulatory pathway(s) in the Mu50 lineage of Staphylococcus aureus. Methodology and results: Staphylococcus aureus strains Mu50Ω, Mu50Ω-vraSm and Mu50Ω-vraSm-graRm are isogenic strains with ascending levels of vancomycin resistance. Total proteins were extracted from the 3 strains and trypsin digested prior to protein isolation and identification by LC-ESI MS/MS and PLGS 2.4. Expression profiles of resulting proteins were analyzed using Progenesis LC/MS software. Differential expression profiles revealed 3 regulons, each controlled by VraS (Mu50Ω-vraSm vs Mu50Ω), GraR (Mu50Ω-vraSm-graRm vs Mu50Ω-vraSm) and VraS-GraR (Mu50Ω-vraSm-graRm vs Mu50Ω), respectively. The regulon down-regulated by VraS in Mu50Ω-vraSm were proteins associated with virulence (MgrA, Rot, and SarA), while GraR up-regulated resistance-associated proteins (TpiA, ArcB and IsaA) in Mu50Ω-vraSm-graRm. The VraS-GraR regulon mediated both up-regulation of resistance-associated proteins (ArgF, ArcB, VraR and SerS) and down-regulation of virulence-associated protein GapB. Conclusion, significance and impact of study: Down-regulation of virulence- in concert with up-regulation of resistance-associated proteins appears to be integral for development of intermediate-vancomycin resistance in the Mu50 lineage of S. aureus.

KW - Proteomics profiling

KW - Staphylococcus aureus

KW - Vancomycin-intermediate

KW - Virulence

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