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.
Subject(s)
Staphylococcus aureusABSTRACT
Hantaviruses belong to the genus Hantavirus and Hantaan, Seoul, Puumala, Belgrade and Sin Nombre viruses are the etiolgic agents of two serious hantaviral diseases of humans. The rodent hosts and the specific etiologic agents of haemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) are known and many reported cases occurred in Eurasia and Americas. Wild rodents trapped in 13 different areas of Korea from 1994 to 1998 were investigated against hantavirus infection. A total of 718 wild rodents and 10 species were trapped and found 630 (87.7%) of them were Apodemus agrarius. Indirect immunofluorescent antibody technique (IFAT) was performed for hantaviruses infections using different hantavirus antigens. Hantavirus antibodies were found in 68 (10.8%) out of 630 A. agrarius, 8 (42.1%) of 19 Rattus norvegicus. Among 68 lungs and other tissues of antibody positive A. agrarius, 5 (7.4%) were antigen positive. IFA titers of 5 positive A. agrarius sera showed higher titers against Puumala or Sin Nombre viruses than Hantaan virus. These results suggest that there may be are possibilities of existence of a noble hantavirus in Korean wild rodents.
Subject(s)
Animals , Humans , Rats , Americas , Antibodies , Fever , Hantaan virus , Hantavirus Infections , Hantavirus Pulmonary Syndrome , Orthohantavirus , Hemorrhagic Fever with Renal Syndrome , Korea , Lung , Murinae , Rodentia , Seoul , Sin Nombre virusABSTRACT
No Abstract Available.