Rearrangement of a large novel Pseudomonas aeruginosa gene island in strains isolated from a patient developing ventilator-associated pneumonia.
Bacterial gene islands add to the genetic repertoire of opportunistic pathogens. Here, we perform comparative analyses of three Pseudomonas aeruginosa strains isolated sequentially over a 3-week period from a patient with ventilator-associated pneumonia (VAP) who received clindamycin and piperacillin-tazobactam as part of their treatment regime. While all three strains appeared to be clonal by standard pulsed-field gel electrophoresis, whole-genome sequencing revealed subtle alterations in the chromosomal organization of the last two strains; specifically, an inversion event within a novel 124-kb gene island (PAGI 12) composed of 137 open reading frames [ORFs]. Predicted ORFs in the island included metabolism and virulence genes. Overexpression of a gene island-borne putative β-lactamase gene was observed following piperacillin-tazobactam exposure and only in those strains that had undergone the inversion event, indicating altered gene regulation following genomic remodeling. Examination of a separate cohort of 76 patients with VAP for integration at this tRNA(lys) recombination site demonstrated that patients exhibiting evidence of integration at this site had significantly higher 28-day mortality. These findings provide evidence that P. aeruginosa can integrate, rapidly remodel, and express exogenous genes, which likely contributes to its fitness in a clinical setting.
Department of Anesthesia and Perioperative Care, University of California-San Francisco, San Francisco, California, USA.
G
G
Singh
Division of Gastroenterology, Department of Medicine, University of California-San Francisco, San Francisco, California, USA.
R
R
Srinivasan
Joint Genome Institute, Walnut Creek, California, USA Lawrence Berkeley National Laboratory, Berkeley, California, USA.
J
J
Cheng
Joint Genome Institute, Walnut Creek, California, USA Lawrence Berkeley National Laboratory, Berkeley, California, USA.
Z
Z
Peng
Division of Gastroenterology, Department of Medicine, University of California-San Francisco, San Francisco, California, USA.
K
K
Fujimura
Department of Anesthesia and Perioperative Care, University of California-San Francisco, San Francisco, California, USA.
M S
MS
Baek
Department of Anesthesia and Perioperative Care, University of California-San Francisco, San Francisco, California, USA.
A R
AR
Panzer
Joint Genome Institute, Walnut Creek, California, USA.
S G
SG
Tringe
Joint Genome Institute, Walnut Creek, California, USA.
F
F
Chen
Joint Genome Institute, Walnut Creek, California, USA.
R
R
Sorek
Joint Genome Institute, Walnut Creek, California, USA.
L
L
Weng
Joint Genome Institute, Walnut Creek, California, USA.
J
J
Bristow
Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
J P
JP
Wiener-Kronish
Division of Gastroenterology, Department of Medicine, University of California-San Francisco, San Francisco, California, USA susan.lynch@ucsf.edu.
S V
SV
Lynch
D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D002981:Clindamycin / Q000627:therapeutic use; D004269:DNA, Bacterial / Q000235:genetics; D016521:Electrophoresis, Gel, Pulsed-Field; D015321:Gene Rearrangement; D014644:Genetic Variation; D016680:Genome, Bacterial; D044404:Genomic Islands; D006801:Humans; D008137:Longitudinal Studies; D058889:Molecular Typing; D010397:Penicillanic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D010878:Piperacillin / Q000627:therapeutic use; D000077725:Piperacillin, Tazobactam Drug Combination; D053717:Pneumonia, Ventilator-Associated / Q000188:drug therapy / Q000382:microbiology*; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D017422:Sequence Analysis, DNA
D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D000077725:Piperacillin, Tazobactam Drug Combination; D002981:Clindamycin; D010397:Penicillanic Acid; D010878:Piperacillin