عنوان

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

TLets659260

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

[Thesis]

Jones, Lim Stephen

Cardiff University

2015

Thesis (Ph.D.)

2015

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.

QR Microbiology ; RA0421 Public health. Hygiene. Preventive Medicine

Jones, Lim Stephen

Cardiff University

p

[Thesis]

276903

a

Y