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Title: The role of international 'high-risk clones' in the emergence of metallo-β-lactamase-producing Pseudomonas aeruginosa in the UK
Author: Wright, Laura L.
ISNI:       0000 0004 5915 6878
Awarding Body: University of East Anglia
Current Institution: University of East Anglia
Date of Award: 2015
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Pseudomonas aeruginosa is a Gram-negative bacterium responsible for a wide range of opportunistic hospital-acquired infections. However metallo-β-lactamases (MBLs) encoding resistance to carbapenems and other β-lactam antibiotics – which are important agents for the treatment of P. aeruginosa infections – are increasingly reported in the species worldwide. This study aimed to characterise a comprehensive collection of MBL-producing P. aeruginosa referred to the UK national reference laboratory from 267 patients between 2003 and 2012. VIM-type MBLs predominated (91%) but a few IMP- and NDM-type enzymes were also identified. Diverse types were identified amongst these isolates using nine-locus variable number tandem-repeat (VNTR) analysis, but the majority (85%) belonged to six major complexes, corresponding to sequence types (STs) 111, 233, 235, 357,654/964 and 773, respectively, by multi-locus sequence typing (MLST). These are all‘high-risk clones’ frequently reported internationally as hosts of MBLs. blaVIM- and blaIMP-MBL genes were carried in diverse class 1 integron structures; the six most common integron structures (I-VI) carried blaVIM-2 (n=5) or blaVIM-6 (n=1) genes; four were associated with single STs (I, ST111; III, ST773; IV, ST654/964; V,ST357) while two integrons types (II,VI) were seen in multiple STs. Five of these six integrons were located on the P. aeruginosa chromosome, while one (VI) was located on a plasmid. VIM-encoding genomic islands were characterised in representatives of STs 111, 233 and 235 using whole genome sequencing (WGS) methods. SNP analysis achieved greater discrimination among MBL-producing representatives of STs 111 and 235. CRISPR-Cas bacterial defence systems were absent from all sequenced representatives of STs 111 and 235 but were present in single representatives of STs 233, 357, 654 and 773. Overall, ‘high-risk clones’ are important in the spread of MBL-producing P. aeruginosa in the UK. Future work should focus on further elucidating the reasons for the success of these clones, to better understand how to limit the spread of these multi-drug resistant organisms.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available