ABSTRACT
Reduced vancomycin susceptibility in Staphylococcus aureus can cause serious problems relating to treatment failure and persistent infection. We investigated vancomycin susceptibility, genetic relationships and transcriptional changes of the accessory gene regulator (agr) in vancomycin-intermediate S. aureus (VISA) strains isolated from South Korea compared with vancomycin-susceptible S. aureus (VSSA) strains. Molecular characterization, population analysis profiling, agr sequencing and transcriptional profiling of RNAIII by real-time RT-PCR were performed. Of 16 VISA strains tested, eight exhibited ST5, agr II and type II SCCmec. The others exhibited ST239, agr I and type III SCCmec. A point mutation in AgrA (Asp8Gly or Ile238Lys) was found in only five VISA strains; no mutations were detected in the other strains. However, RNAIII levels markedly decreased in all VISA strains (mean of 1.39-fold change) compared with the VSSA strains (31.51-fold change) in late-exponential phases (P<0.0001). The downregulation of RNAIII could be an important genetic event in the VISA strains, regardless of the presence or absence of the agr mutation.
Subject(s)
Bacterial Proteins/biosynthesis , Bacterial Proteins/genetics , Gene Expression Regulation, Bacterial , Mutation, Missense , Staphylococcus aureus/drug effects , Staphylococcus aureus/physiology , Trans-Activators/biosynthesis , Trans-Activators/genetics , Vancomycin Resistance , Anti-Bacterial Agents/pharmacology , DNA, Bacterial/chemistry , DNA, Bacterial/genetics , Down-Regulation , Gene Expression Profiling , Humans , Microbial Sensitivity Tests , Molecular Sequence Data , Molecular Typing , Republic of Korea , Sequence Analysis, DNA , Staphylococcal Infections/microbiology , Staphylococcus aureus/genetics , Staphylococcus aureus/isolation & purification , Vancomycin/pharmacologyABSTRACT
We report a 52-yr-old Korean woman with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) whose diagnosis was confirmed by skin biopsy and the presence of a novel mutation in the NOTCH3 gene. The patient's clinical features were rather unusual in that 1) clinical presentations were only two episodes of stroke and mild dementia unaccompanied by mood disturbances or migraine, and 2) there was no family history. Brain MRI showed T2 hyperintensities in both temporal pole areas in line with the recent suggestion by O'Sullivan et al. that the abnormality could be a radiologic marker of CADASIL. FDG-PET also showed a hypometabolism in the temporal pole areas with an abnormal finding on MRI in addition to the hypometabolism in cortical and subcortical regions. We could learn from this case that CADASIL may be included in the differential diagnoses in patients with vascular dementia associated with a small vessel disease, even in the absence of a family history, especially when there are no known stroke risk factors and when the MRI shows T2 hyperintensity in the temporal pole regions.
