PMID:14977975

Citation	Smith, RS, Wolfgang, MC and Lory, S (2004) An adenylate cyclase-controlled signaling network regulates Pseudomonas aeruginosa virulence in a mouse model of acute pneumonia. Infect. Immun. 72:1677-84
Abstract	Infections caused by the opportunistic pathogen Pseudomonas aeruginosa involve the interplay of several bacterial virulence factors. It has recently been established that the delivery of toxic effector proteins by the type III secretion system is an important virulence mechanism in several animal models. Furthermore, the expression of the type III secretion system and its effectors has been correlated with a poor clinical outcome during human infections. A novel cyclic AMP (cAMP) regulatory network that controls the expression of virulence factors, including the type III secretion system, was examined to determine its contribution to P. aeruginosa colonization and dissemination in a mouse pneumonia model. Mutants lacking the two genome-encoded adenylate cyclases, CyaA and CyaB, and the cAMP-dependent regulator Vfr were examined. Based on the enumeration of bacteria in lungs, livers, and spleens, as well as the assessment of mouse lung pathology, mutations in the cyaB and vfr genes resulted in a more significantly attenuated phenotype than mutations in cyaA. Moreover, in this model, expression of the type III secretion system was essential for lung colonization and pathology. Strains with mutations in the exsA gene, which encodes a type III regulatory protein, or pscC, which encodes an essential component of the secretion apparatus, were also significantly attenuated. Finally, we demonstrate that virulence can be restored in an adenylate cyclase mutant by the overexpression of exsA, which specifically restores expression of the type III secretion system in the absence of a functional cAMP-dependent regulatory network.
Links	PubMed PMC356001
Keywords	Adenylyl Cyclases/genetics; Adenylyl Cyclases/metabolism; Animals; Bacterial Proteins/genetics; Bacterial Proteins/metabolism; Cyclic AMP Receptor Protein/genetics; Cyclic AMP Receptor Protein/metabolism; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Disease Models, Animal; Female; Genes, Bacterial; Humans; Mice; Mice, Inbred BALB C; Mutation; Phenotype; Pneumonia, Bacterial/etiology; Pneumonia, Bacterial/microbiology; Pneumonia, Bacterial/pathology; Pseudomonas Infections/etiology; Pseudomonas Infections/microbiology; Pseudomonas Infections/pathology; Pseudomonas aeruginosa/enzymology; Pseudomonas aeruginosa/genetics; Pseudomonas aeruginosa/pathogenicity; Signal Transduction; Trans-Activators/genetics; Trans-Activators/metabolism; Transcription Factors/genetics; Transcription Factors/metabolism; Virulence/genetics; Virulence/physiology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
PSEAE:VFR	involved_in	GO:0009405: pathogenesis	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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