Genetic diversity of predominant nosocomial meticillin-resistant Staphylococcus aureus lineages in the United Kingdom

Desai, Darshana (2014). Genetic diversity of predominant nosocomial meticillin-resistant Staphylococcus aureus lineages in the United Kingdom. PhD thesis The Open University.



Meticillin-resistant Staphylococcus aureus (MRSA) is one of the major human pathogens and is a common cause of hospital-associated infection in immunocompromised patients and individuals with open wounds. However, infections affecting the healthy and young have increased in the past few decades and are a rising clinical concern. Understanding the genetic diversity of S.aureus can therefore result in a better understanding of the pathogenesis, spread and evolution of S.aureus, which in turn can lead to the development of effective infection control measures. In the present study, molecular methods were utilised to investigate differences in the distribution and variability of bacterial genes present between successful and unsuccessful lineages of MRSA. Lineages were assigned based on multilocus sequence typing (MLST) clonal complexes and successful lineages were defined as those lineages that have given rise to multiple epidemic MRSA done. In addition to well-established molecular methods such as MLST and staphylococcal cassette chromosome mec typing, a novel fluorescent amplified fragment length polymorphism assay was developed to identify regions of genetic heterogeneity between and within lineages. These differences were attributed to lineage-specific sequence variation and differences in the distribution of mobile genetic elements (MGEs) between lineages. These genetic differences were investigated in relation to functional differences within the bacterium, to explore the,role of cell functions encoded by these regions in the emergence and prevalence (or spread) of dominant genetic lineages. This study indicates a combination of factors play a role in the success of major MRSA lineages. The genetic diversity amongst core regions and MGEs appear to alter antimicrobial resistance and virulence factors that are vital to their success, as they enable the rapid adaption of lineages to their environment.

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