Comparative proteomics profiling reveals down-regulation of Staphylococcus aureus virulence in achieving intermediate vancomycin resistance
- Author:
Xin-Ee Tan
;
Hui-min Neoh
;
Mee-Lee Loo
;
Toh Leong Tan
;
Salasawati Hussin
;
Longzhu Cui
;
Keiichi Hiramatsu
;
Rahman Jamal
- Publication Type:Journal Article
- Keywords:
vancomycin-intermediate;
Staphylococcus aureus;
virulence;
proteomics profiling
- MeSH:
Staphylococcus aureus
- From:Malaysian Journal of Microbiology
2016;12(6):498-505
- CountryMalaysia
- Language:English
-
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.
- Full text:P020170203382054579947.pdf
