Comparative Genomics of Pseudomonas Aeruginosa

This project is complete.

Goals

The major objective is comparative genomics of a clinical isolate ofPseudomonas aeruginosa that is resistant to quinolones and third-generation cephalosporins. Preliminary sequencing of resistance-associated genes and several other genes indicate that this strain is a taxonomic outlier, that differs greatly from the sequenced strains PAO1 and PA14, and practically at the limit of the definition of a species. The overall goals are to identify, from a genomic sequence, genes associated with resistance and virulence, and other islands or individual genes that are absent in the type strain PAO1 and the closely related strain PA14.

Rationale

Pseudomonas aeruginosa has been described as the first Gram-negative "superbug". The PA7 clinical isolate has a particularly interesting resistance profile. This strain is highly resistant to third generation cephalosporins (MIC for ceftazidime of 128 µg/ml), monobactams (MIC for aztreonam of 64 µg/ml), and fluoroquinolones (MIC for ciprofloxacin of 128 µg/ml). The strain is also resistant to piperacillin, carbenicillin, levofloxacin and chloramphenicol, but sensitive to carbapenems (MIC for imipenem of 2 µg/ml and for meropenem of 1 µg/ml). No integron was found in this strain, although integrons were present in other isolates from the same site. The sequence of the genes encoding DNA gyrase and topoisimerase IV reveals some point mutations described in the literature as having a role in fluoroquinolone resistance, but many more amino acid differences that may or may not be related to resistance. The same is true for genes involved in Beta-lactam resistance and in multidrug efflux.

The PA7 strain is one of a collection of 10 non-respiratory isolates (3 from Thailand; 7 including PA7 from the Malbran Institute in Buenos Aires, Argentina) that were collected for their unusual resistance patterns.

Pseudomonas aeruginosa PA7