Dataset Information

Genetic pathway in acquisition and loss of vancomycin resistance in a methicillin resistant Staphylococcus aureus (MRSA) strain of clonal type USA300.

ABSTRACT: An isolate of the methicillin-resistant Staphylococcus aureus (MRSA) clone USA300 with reduced susceptibility to vancomycin (SG-R) (i.e, vancomycin-intermediate S. aureus, VISA) and its susceptible "parental" strain (SG-S) were recovered from a patient at the end and at the beginning of an unsuccessful vancomycin therapy. The VISA phenotype was unstable in vitro generating a susceptible revertant strain (SG-rev). The availability of these 3 isogenic strains allowed us to explore genetic correlates of antibiotic resistance as it emerged in vivo. Compared to the susceptible isolate, both the VISA and revertant strains carried the same point mutations in yycH, vraG, yvqF and lspA genes and a substantial deletion within an intergenic region. The revertant strain carried a single additional frameshift mutation in vraS which is part of two component regulatory system VraSR. VISA isolate SG-R showed complex alterations in phenotype: decreased susceptibility to other antibiotics, slow autolysis, abnormal cell division and increased thickness of cell wall. There was also altered expression of 239 genes including down-regulation of major virulence determinants. All phenotypic properties and gene expression profile returned to parental levels in the revertant strain. Introduction of wild type yvqF on a multicopy plasmid into the VISA strain caused loss of resistance along with loss of all the associated phenotypic changes. Introduction of the wild type vraSR into the revertant strain caused recovery of VISA type resistance. The yvqF/vraSR operon seems to function as an on/off switch: mutation in yvqF in strain SG-R turns on the vraSR system, which leads to increase in vancomycin resistance and down-regulation of virulence determinants. Mutation in vraS in the revertant strain turns off this regulatory system accompanied by loss of resistance and normal expression of virulence genes. Down-regulation of virulence genes may provide VISA strains with a "stealth" strategy to evade detection by the host immune system.

SUBMITTER: Gardete S

PROVIDER: S-EPMC3271070 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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Publications

Genetic pathway in acquisition and loss of vancomycin resistance in a methicillin resistant Staphylococcus aureus (MRSA) strain of clonal type USA300.

Gardete Susana S Kim Choonkeun C Hartmann Boris M BM Mwangi Michael M Roux Christelle M CM Dunman Paul M PM Chambers Henry F HF Tomasz Alexander A

PLoS pathogens 20120202 2

An isolate of the methicillin-resistant Staphylococcus aureus (MRSA) clone USA300 with reduced susceptibility to vancomycin (SG-R) (i.e, vancomycin-intermediate S. aureus, VISA) and its susceptible "parental" strain (SG-S) were recovered from a patient at the end and at the beginning of an unsuccessful vancomycin therapy. The VISA phenotype was unstable in vitro generating a susceptible revertant strain (SG-rev). The availability of these 3 isogenic strains allowed us to explore genetic correlat ...[more]

PMID: 22319446

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Project description:Although methicillin (meticillin)-resistant Staphylococcus aureus (MRSA) strains with reduced susceptibility to vancomycin (RVS-MRSA; including vancomycin-intermediate S. aureus [VISA] and heterogeneous VISA [hVISA]) have been linked with vancomycin treatment failure, it is unclear whether they are more pathogenic than vancomycin-susceptible MRSA (VS-MRSA). We prospectively assessed patients with clinical MRSA isolates during a 10-month period to determine clinical status (infection versus colonization) and therapeutic outcome before correlating these findings with the results of detailed in vitro assessment of vancomycin susceptibility, including population analysis profile (PAP) testing. hVISA and VISA were defined by standard PAP criteria (area-under-the-curve ratio compared to that of the reference hVISA strain Mu3 [>or=0.9]) and routine CLSI criteria (vancomycin MIC, 4 to 8 microg/ml), respectively. Among the 117 patients assessed, 58 had RVS-MRSA isolates (56 hVISA and 2 VISA) and 59 had VS-MRSA isolates; the patient demographics and comorbidities were similar. RVS-MRSA was associated with a lower rate of infection than VS-MRSA (29/58 versus 46/59; P = 0.003), including a lower rate of bacteremia (3/58 versus 20/59, respectively; P < 0.001). The cure rates in RVS-MRSA and VS-MRSA groups were not statistically different (16/26 versus 31/42; P = 0.43), but the post hoc assessment of treatment regimes and study size made detailed conclusions difficult. The results of the macro method Etest correlated well with the PAP results (sensitivity, 98.3%, and specificity, 91.5%), but broth microdilution and our preliminary RVS-MRSA detection method correlated poorly. All isolates were susceptible to linezolid and daptomycin. These data suggest that detailed prospective laboratory identification of RVS-MRSA isolates may be of limited value and that, instead, such in vitro investigation should be reserved for isolates from patients who are failing appropriate anti-MRSA therapy.

Dataset Information

Genetic pathway in acquisition and loss of vancomycin resistance in a methicillin resistant Staphylococcus aureus (MRSA) strain of clonal type USA300.

Publications

Genetic pathway in acquisition and loss of vancomycin resistance in a methicillin resistant Staphylococcus aureus (MRSA) strain of clonal type USA300.

Similar Datasets

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