PMID:8698507

Citation	Yu, H, Boucher, JC, Hibler, NS and Deretic, V (1996) Virulence properties of Pseudomonas aeruginosa lacking the extreme-stress sigma factor AlgU (sigmaE). Infect. Immun. 64:2774-81
Abstract	A discerning feature of Pseudomonas aeruginosa strains causing chronic endobronchial infections in cystic fibrosis is their conversion into the mucoid, exopolysaccharide alginate-overproducing phenotype. This morphologically prominent change is caused by mutations which upregulate AlgU (sigma(E)), a novel extreme-stress sigma factor with functional equivalents in gram-negative organisms. In this work, we investigated the role of algU in P. aeruginosa sensitivity to reactive oxygen intermediates, killing by phagocytic cells, and systemic virulence of this bacterium. Inactivation of algU in P. aeruginosa PA01 increased its susceptibility to killing by chemically or enzymatically generated halogenated reactive oxygen intermediates and reduced its survival in bactericidal assays with J774 murine macrophages and human neutrophils. Surprisingly, inactivation of algU caused increased systemic virulence of P. aeruginosa in mouse models of acute infection. The increased lethality of the algU-deficient strain was also observed in the endotoxin-resistant C3H/HeJ mice. Only minor differences between algU+ and algU mutant cells in their sensitivity to human serum were observed, and no differences in their lipopolysaccharide profiles were detected. Intriguingly, while inactivation of algU downregulated five polypeptides it also upregulated the expression of seven polypeptides as determined by two-dimensional gel analyses, suggesting that algU plays both a positive and a negative role in gene expression in P. aeruginosa. While the observation that algU inactivation increases systemic virulence in P. aeruginosa requires further explanation, this phenomenon contrasts with the apparent selection for strains with upregulated AlgU during colonization of the cystic fibrosis lung and suggests opposing roles for this system in chronic and acute infections.
Links	PubMed PMC174138
Keywords	Animals; Bacterial Proteins/genetics; Bacterial Proteins/physiology; Blood Bactericidal Activity; Cystic Fibrosis/complications; Disease Models, Animal; Humans; Hypochlorous Acid/pharmacology; In Vitro Techniques; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mutation; Opportunistic Infections/complications; Opportunistic Infections/etiology; Pseudomonas Infections/complications; Pseudomonas Infections/etiology; Pseudomonas aeruginosa/genetics; Pseudomonas aeruginosa/pathogenicity; Pseudomonas aeruginosa/physiology; Sepsis/etiology; Sepsis/microbiology; Sigma Factor/genetics; Sigma Factor/physiology; Virulence/genetics; Virulence/physiology
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Annotations

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

References

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