The influence of human respiratory epithelia on Pseudomonas aeruginosa gene expression.
The opportunistic pathogen Pseudomonas aeruginosa can cause acute or chronic infections in humans. Little is known about the initial adaptation of P. aeruginosa to host tissues and the factors that determine whether a P. aeruginosa-epithelial cell interaction will manifest as an acute or a chronic infection. To gain insights into the initial phases of P. aeruginosa infections and to identify P. aeruginosa genes regulated in response to respiratory epithelia, we exposed P. aeruginosa to cultured primary differentiated human airway epithelia. We used a P. aeruginosa strain that causes acute damage to the epithelia and a mutant with defects in Type III secretion and in rhamnolipid synthesis. The mutant did not cause rapid damage to epithelia as did the wildtype. We compared the transcriptomes of the P. aeruginosa wildtype and the mutant to each other and to P. aeruginosa grown under other conditions, and we discovered overlapping sets of differentially expressed genes in the wildtype and mutant exposed to epithelia. A recent study reported that exposure of P. aeruginosa to epithelia is characterized by a repression of the bacterial iron-responsive genes. These findings were suggestive of ample iron availability during infection. In contrast, we found that P. aeruginosa shows an iron-starvation response upon exposure to epithelial cells. This observation highlights the importance of the iron starvation response in both acute and chronic infections and suggests opportunities for therapy.
Chugani
Sudha
S
Department of Microbiology, University of Washington, 1959 NE Pacific St., HSB I-420, Seattle, WA 98195, USA.
Greenberg
E P
EP
D000208:Acute Disease; D002908:Chronic Disease; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D006017:Glycolipids / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D007501:Iron / Q000378:metabolism; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D011552:Pseudomonas Infections / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000235:genetics* / Q000472:pathogenicity; D020545:Respiratory Mucosa / Q000166:cytology / Q000382:microbiology*; D014158:Transcription, Genetic; D037521:Virulence Factors / Q000235:genetics
D006017:Glycolipids; D037521:Virulence Factors; C051310:rhamnolipid hemolysin, Pseudomonas aeruginosa; D007501:Iron