ABSTRACT
It is known that multiple genome-wide transcriptional changes often accompany the development of antimicrobial resistance and occur in response to challenge with antimicrobial agents. We now show that inactivation of the staphylococcal accessory gene regulator sarA, which controls at least tens of genes in Staphylococcus aureus, leads to dramatic reductions in vancomycin and ciprofloxacin resistance in vancomycin-intermediate and ciprofloxacin-resistant strains of S. aureus. This is particularly evident when judged by antimicrobial-gradient plate analysis or population analysis profiles. Whilst the intact sarA cistron is required for full vancomycin resistance expression by vancomycin-intermediate S. aureus (VISA), sarA expression as determined by quantitative real-time polymerase chain reaction was found to be VISA strain-dependent. Reductions in vancomycin resistance expression levels following sarA inactivation do not necessarily include an alteration in autolysis. Expression of sarR, the negative regulator of sarA, was downregulated in two VISA mutants, and transcription of the alternative sigma factor sigB was downregulated in one VISA strain. This study contributes to a growing body of evidence demonstrating the importance of loci previously identified to control virulence in the regulation of clinically relevant antibiotic resistance mechanisms.
Subject(s)
Anti-Bacterial Agents/pharmacology , Bacterial Proteins/metabolism , Ciprofloxacin/pharmacology , Drug Resistance, Bacterial , Staphylococcus aureus/drug effects , Staphylococcus aureus/physiology , Vancomycin/pharmacology , Bacterial Proteins/genetics , Gene Deletion , Gene Expression Profiling , Gene Expression Regulation, Bacterial , Microbial Sensitivity Tests , Staphylococcus aureus/genetics , Vancomycin ResistanceABSTRACT
A survey of 152 methicillin-resistant Staphylococcus aureus (MRSA) strains from medical centers in Las Cruces, NM, and El Paso, TX, revealed the presence of spa types 2 and 24 (clone USA100) and spa type 1 (clone USA300-0114). Las Cruces MRSA displayed relatively high vancomycin MICs, and one hetero-vancomycin-intermediate S. aureus strain was identified.
Subject(s)
Drug Resistance, Multiple, Bacterial , Methicillin Resistance , Staphylococcal Infections/microbiology , Staphylococcus aureus/drug effects , Vancomycin Resistance , Anti-Bacterial Agents/pharmacology , Cluster Analysis , Colony Count, Microbial , DNA Fingerprinting , DNA, Bacterial/genetics , Electrophoresis, Gel, Pulsed-Field , Hospitals , Humans , Microbial Viability , New Mexico , Staphylococcus aureus/classification , Staphylococcus aureus/isolation & purification , Staphylococcus aureus/physiology , TexasABSTRACT
Seventy-one percent of 76 methicillin-resistant Staphylococcus aureus (MRSA) strains isolated from two medical centers in El Paso, Texas, represent three similar pulsed-field gel electrophoresis types. Overall, six pulsed-field types were identified represented by multilocus sequence/staphylococcal chromosomal cassette DNA mec (SCCmec) types: ST5-MRSA-II; ST36-MRSA-II; ST8 (untypeable SCCmec); and a newly described clonal cluster 8 strain, ST507-MRSA-IV. This study demonstrates the presence of multiple-antibiotic-resistant epidemic MRSA clones in El Paso.
