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Title: Why are methicillin-resistant staphylococcus aureau (MRSA) not fully drug-resistant?
Author: Budd, Emma Louise
Awarding Body: St George's, University of London
Current Institution: St George's, University of London
Date of Award: 2012
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Staphylococcus aureus is an opportunistic pathogen in UK hospitals and MRSA is a major concern due to burgeoning multi-drug resistance. However these resistance genotypes have not accumulated into one fully-resistant MRSA clone. MRSA from St. George's Healthcare NHS trust (SGHT) over a period of ten years were investigated. Antibiotic resistance phenotypes, genotypes and lineage types of infective MRSA isolates, incidence of MRSA, records of antibiotic prescribing both before and after a change in antibiotic stewardship and implementation dates of infection control interventions were combined. These data established that a decline in MRSA incidence correlated with a decrease in prescription of fluoroquinolones and cephalosporins at SGHT and no other recorded infection control intervention. CC22 MRSA became the dominant lineage of MRSA at SGHT from 2006 onwards, this coincided with the sudden acquisition of new antibiotic resistances by this lineage and the ability to gain and lose these resistances in subsequent years. These changes did not correlate with a change in antibiotic stewardship and could not be associated with any other infection control intervention. No MRSA were fully drug resistant, the majority were multi-drug resistant. However resistance did not accumulate within any lineage over time. Antibiotic resistance genes in MRSA are often carried on mobile genetic elements (MGEs). Resistance genotypes of infective MRSA suggested that carriage of resistance genes differs between lineages. Barriers to horizontal gene transfer (HGT) between lineages such as restriction-modification systems have been previously characterised using laboratory isolates of S. aureus and restriction-deficient mutants. The effect of these barriers on the spread of naturally occurring MGEs between clinical MRSA has 3 • not been measured. The efficiency of barriers to HGT between clinical MRSA lineages was assessed by developing an in vitro model conjugation. A conjugative gentamicin resistance plasmid was transferred at high frequency within a lineage, but at low frequency between lineages. Barriers to HGT were also assessed by attempting to develop an in vitro model of transduction. Phage from isolated from local water sources were used to transfer antibiotic resistance genes within and between lineages of clinical MRSA by generalised transduction. Transduction was detected between clinical MRSA of different lineages at low frequency, however transductions were broadly unsuccessful. Further investigation is warranted as generalised transduction appears to be an important mechanism by which antibiotic resistance genes are exchanged among MRSA. The presence of efficient barriers to HGT in clinical MRSA contributes to our understanding of why antibiotic resistance has not been able to accumulate in MRSA and why we have not seen a fully drug resistant S. aureus. ", •
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available