ABSTRACT
The 3.1-Mb genome of an outbreak methicillin-resistant Staphylococcus aureus (MRSA) strain (TW20) contains evidence of recently acquired DNA, including two large regions (635 kb and 127 kb). The strain is resistant to a wide range of antibiotics, antiseptics, and heavy metals due to resistance genes encoded on mobile genetic elements and also mutations in housekeeping genes.
Subject(s)
Drug Resistance, Multiple, Bacterial/genetics , Genome, Bacterial/genetics , Methicillin-Resistant Staphylococcus aureus/genetics , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents, Local/pharmacology , Metals, Heavy/toxicity , Methicillin-Resistant Staphylococcus aureus/drug effects , Models, Genetic , Molecular Sequence DataABSTRACT
Multilocus sequence typing (MLST) and multi-strain microarray analysis have shown that most human Staphylococcus aureus strains belong to ten dominant clonal complexes (CCs) or lineages, each with unique surface architecture. Meticillin-resistant S. aureus (MRSA) strains currently belong to six of these lineages (CC1, CC5, CC8, CC22, CC30 and CC45), each of which has independently acquired mobile genetic elements (MGEs) carrying antibiotic resistance genes. MLST and microarrays are expensive and time consuming methods for routine determination of S. aureus lineage. A restriction-modification (RM) test has now been developed that is rapid, simple, inexpensive and accurately determines lineage of hospital-acquired MRSA. The RM test is based on three PCRs for hsdS gene variants, as hsdS genes likely control the independent evolution of S. aureus lineages. The RM test correctly identified 102 MRSA isolates as belonging to one of the six lineages/CCs. Real-time MRSA typing can be used to identify and track changes in local MRSA outbreaks, and provide support for targeting infection control strategies. Simple and accurate typing methods will also support large scale epidemiological studies, and could lead to greater understanding of the carriage, spread and virulence of different MRSA lineages.
Subject(s)
Cross Infection/microbiology , Deoxyribonucleases, Type I Site-Specific/genetics , Methicillin Resistance , Polymerase Chain Reaction/methods , Staphylococcal Infections/microbiology , Staphylococcus aureus/classification , DNA Restriction-Modification Enzymes/genetics , DNA, Bacterial/genetics , Humans , Molecular Epidemiology/methods , Sensitivity and Specificity , Staphylococcus aureus/drug effects , Staphylococcus aureus/genetics , Staphylococcus aureus/isolation & purificationABSTRACT
BACKGROUND: Patients in intensive care units are at high risk of developing methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. We report an epidemiological and bacterial genomic analysis of a 2-year outbreak in an intensive care unit of a variant of MRSA sequence type 239 (hereafter designated TW). METHODS: A cohort study was conducted to compare risk factors for MRSA bacteremia in patients who acquired TW versus patients who acquired non-TW strains of MRSA. Genetic analysis of TW was performed using multilocus sequence typing and microarray analysis. RESULTS: Patients who acquired TW were more likely than patients who acquired non-TW strains of MRSA to have MRSA isolated from blood samples (47% vs. 13%; P<.001) and to have MRSA-positive vascular access device-sample cultures (59% vs. 26%; P<.001), but less likely to have MRSA isolated from screening swab samples (30% vs. 71%; P<.001). This increased rate of TW bacteremia was confined to the first week after acquisition of TW infection. Using Cox regression analysis, the adjusted hazard ratio for bacteremia with TW was 4.5 times that of non-TW strains of MRSA (95% confidence interval, 2.25-9.00; P<.001). Microarray analysis revealed that TW had accumulated all detectable mobile genetic elements that were variably expressed by other epidemic strains of MRSA sequence type 239 in the United Kingdom. CONCLUSIONS: To our knowledge, this is the first report to provide direct evidence that strains of MRSA can differ in their ability to cause bacteremia. Further genetic and in vitro analysis of the TW strain may provide insight into the mechanism of vascular access device-related bacteremia in the intensive care unit environment.
