PMID:24491574

Citation	Sun, Z, Shi, J, Liu, C, Jin, Y, Li, K, Chen, R, Jin, S and Wu, W (2014) PrtR homeostasis contributes to Pseudomonas aeruginosa pathogenesis and resistance against ciprofloxacin. Infect. Immun. 82:1638-47
Abstract	Pseudomonas aeruginosa is an opportunistic pathogen that causes acute and chronic infections in humans. Pyocins are bacteriocins produced by P. aeruginosa that are usually released through lysis of the producer strains. Expression of pyocin genes is negatively regulated by PrtR, which gets cleaved under SOS response, leading to upregulation of pyocin synthetic genes. Previously, we demonstrated that PrtR is required for the expression of type III secretion system (T3SS), which is an important virulence component of P. aeruginosa. In this study, we demonstrate that mutation in prtR results in reduced bacterial colonization in a mouse acute pneumonia model. Examination of bacterial and host cells in the bronchoalveolar lavage fluids from infected mice revealed that expression of PrtR is induced by reactive oxygen species (ROS) released by neutrophils. We further demonstrate that treatment with hydrogen peroxide or ciprofloxacin, known to induce the SOS response and pyocin production, resulted in an elevated PrtR mRNA level. Overexpression of PrtR by a tac promoter repressed the endogenous prtR promoter activity, and electrophoretic mobility shift assay revealed that PrtR binds to its own promoter, suggesting an autorepressive mechanism of regulation. A high level of PrtR expressed from a plasmid resulted in increased T3SS gene expression during infection and higher resistance against ciprofloxacin. Overall, our results suggest that the autorepression of PrtR contributes to the maintenance of a relatively stable level of PrtR, which is permissive to T3SS gene expression in the presence of ROS while increasing bacterial tolerance to stresses, such as ciprofloxacin, by limiting pyocin production.
Links	PubMed PMC3993409 Online version:10.1128/IAI.01388-13
Keywords	Acute Disease; Animals; Anti-Bacterial Agents/pharmacology; Bacterial Proteins/genetics; Bacterial Proteins/metabolism; Bacterial Proteins/physiology; Biofilms/drug effects; Bronchoalveolar Lavage Fluid/microbiology; Ciprofloxacin/pharmacology; Disease Models, Animal; Drug Resistance, Bacterial/physiology; Female; Gene Expression Regulation, Bacterial; Homeostasis/drug effects; Homeostasis/genetics; Hydrogen Peroxide/metabolism; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Pneumonia, Bacterial/microbiology; Pseudomonas Infections/microbiology; Pseudomonas aeruginosa/drug effects; Pseudomonas aeruginosa/pathogenicity; Pseudomonas aeruginosa/physiology; Pyocins/metabolism; RNA, Messenger/metabolism; Reactive Oxygen Species/metabolism; Repressor Proteins/genetics; Repressor Proteins/metabolism; Repressor Proteins/physiology
edit table

Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
PSEAI:A0A069QIQ9		GO:0009405: pathogenesis	ECO:0000315:		P		Fig. 1. A. Pseudomonas aeruginosa (STRAIN: PAK) PrtR mutant showed lower CFU in mice lungs compared to wild-type when the mice were intranasally inoculated.	complete CACAO 12549

References

See Help:References for how to manage references in GONUTS.