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Title: Heterogeneity of VanA phenotype glycopeptide-resistant enterococci in Scotland
Author: Brown, Alan Reid
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2001
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The aim of this study was to investigate the epidemiology of VanA GRE in Scotland, and to determine the degree of diversity amongst the Tn1546-related elements conferring resistance. GRE were collected over a five-year period from eight hospitals across Scotland. Fifty-five GRE isolates were collected in total, 48 of which were found to be vanA-positive. In addition, a five-month survey of enterococcal epidemiology was performed, during which time 94 enterococcal isolates were collected, two of which were found to be vanA-positive. The Tn1546-related elements, responsible for conferring resistance in the 48 nosocomial VanA GRE, were assessed for diversity. Whilst complete characterisation was not possible for all VanA elements, the majority could be assigned to one of ten different Tn1546-types on the basis of insertion and deletion events. Different Tn1546-types varied in their geographical distribution. The insertion sequence IS1542 and an IS1216V-related element were identified within the orf2-vanR and vanX-vanY intergenic regions respectively. Further variation, at least partly attributable to the presence of an IS1216V-rel;ated element, was common within the orf1/orf2 regions of the transposon. A hybrid promote located upstream of vanR was identified, being generated by the insertion of IS1542 immediately adjacent to the native -10 (TATAAT) box of the vanR promoter. This hybrid promoter is thought to be responsible for low-level constitutive expression of the glycopeptide resistance genes that was seen in those isolates harbouring the IS1542 insertion within the VanA transposon. This hybrid promoter supplements, rather than replaces, the normal inducible expression from the native vanR promoter that follows glycopeptide exposure. A media-dependent increase in the level of teicoplanin resistance was seen in those strains showing the hybrid promoter. Whilst it is thought that this increase is attributable to the hybrid promoter, the exact mechanism is unclear.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available