Defining the Pseudomonas aeruginosa SOS response and its role in the global response to the antibiotic ciprofloxacin.
Pseudomonas aeruginosa infections can be virtually impossible to eradicate, and the evolution of resistance during antibiotic therapy is a significant concern. In this study, we use DNA microarrays to characterize the global transcriptional response of P. aeruginosa to clinical-like doses of the antibiotic ciprofloxacin and also to determine the component that is regulated by LexA cleavage and the SOS response. We find that genes involved in virtually every facet of metabolism are down-regulated in response to ciprofloxacin. The LexA-controlled SOS regulon identified by microarray analysis includes only 15 genes but does include several genes that encode proteins involved in recombination and replication, including two inducible polymerases known to play a role in mutation and the evolution of antibiotic resistance in other organisms. The data suggest that the inhibition of LexA cleavage during therapy might help combat this pathogen by decreasing its ability to adapt and evolve resistance.
Cirz
Ryan T
RT
Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA.
O'Neill
Bryan M
BM
Hammond
Jennifer A
JA
Head
Steven R
SR
Romesberg
Floyd E
FE
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D002939:Ciprofloxacin / Q000494:pharmacology*; D004259:DNA-Directed DNA Polymerase / Q000235:genetics; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D020411:Oligonucleotide Array Sequence Analysis; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000235:genetics*; D012329:RNA, Bacterial / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D045522:Recombinases / Q000235:genetics; D018085:Regulon; D013014:SOS Response, Genetics / Q000235:genetics*; D012697:Serine Endopeptidases / Q000235:genetics; D000099160:LexA Repressor Protein
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002939:Ciprofloxacin; D004259:DNA-Directed DNA Polymerase; D012329:RNA, Bacterial; D012333:RNA, Messenger; D045522:Recombinases; D012697:Serine Endopeptidases; D000099160:LexA Repressor Protein