Mobile genetic elements associated with blaNDM-1 in Acinetobacter spp. and vibrio cholerae.

Jones, Lim Stephen 2015. Mobile genetic elements associated with blaNDM-1 in Acinetobacter spp. and vibrio cholerae. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

NDM-producing bacteria are associated with extensive antimicrobial resistance (AMR). This thesis reports on detailed molecular analysis, including whole genome sequencing, of Acinetobacter spp. and Vibrio cholerae isolates. A study of clinical Acinetobacter baumannii isolates from India, demonstrated spread of a single strain containing blaNDM-1 but with evidence of significant genetic plasticity between isolates. A novel plasmid, pNDM-32, was fully characterised in isolate CHI-32. This contained multiple AMR genes including blaNDM-1 and the aminoglycoside methyltransferase gene armA. A repAci10 replicase gene was identified but no conjugation machinery and the plasmid could not be transferred in conjugation experiments. A single isolate of Acinetobacter bereziniae from India contained plasmid, pNDM-40-1, harbouring blaNDM-1, which was closely related to plasmids from NDM-producing Acinetobacter spp. isolated in China, and was readily transferred into Escherichia coli and Acinetobacter pittii by conjugation. Five blaNDM-1 positive Acinetobacter spp. isolated from a faecal screening study in Pakistan also included three, clonal, Acinetobacter haemolyticus isolates harbouring a similar plasmid. Three environmental V. cholerae strains from India and a blood isolate from a traveller returning to the UK from India were found to include three distantly related strains. 2 isolates of a single strain contained an IncA/C plasmid, pNDM-116-17, harbouring AMR genes including blaNDM-1. In one isolate pNDM-116-17 had become integrated into a chromosomal region containing a SXT-like element. In the other isolates blaNDM-1 and other AMR determinants were localised to a large plasmid, pNDM-116-14, with a novel replicase and a full complement of conjugative transfer genes, and a novel genomic island, SGI-NDM-1. Most previous studies have focused on Enterobacteriaceae. Thecurrent work contributes to an understanding of the full extent of the genetic diversity of blaNDM-1 contexts, and their dissemination. Such knowledge should help to infer factors which contribute to the spread of AMR in bacterial pathogens.

Item Type:	Thesis (PhD)
Date Type:	Completion
Status:	Unpublished
Schools:	Medicine
Subjects:	Q Science > QR Microbiology R Medicine > RA Public aspects of medicine > RA0421 Public health. Hygiene. Preventive Medicine
Date of First Compliant Deposit:	30 March 2016
Last Modified:	22 Aug 2022 15:29
URI:	https://orca.cardiff.ac.uk/id/eprint/74109

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