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cAMP receptor protein regulates mouse colonization, motility, fimbria-mediated adhesion, and stress tolerance in uropathogenic Proteus mirabilis.
- Source :
-
Scientific reports [Sci Rep] 2017 Aug 04; Vol. 7 (1), pp. 7282. Date of Electronic Publication: 2017 Aug 04. - Publication Year :
- 2017
-
Abstract
- Cyclic AMP receptor protein (Crp) is a major transcriptional regulator in bacteria. This study demonstrated that Crp affects numerous virulence-related phenotypes, including colonization of mice, motility, fimbria-mediated adhesion, and glucose stress tolerance in uropathogenic Proteus mirabilis. Diabetic mice were more susceptible to kidney colonization by wild-type strain than nondiabetic mice, in which the crp mutant exhibited increased kidney colonization. Loss of crp or addition of 10% glucose increased the P. mirabilis adhesion to kidney cells. Direct negative regulation of pmpA (which encodes the major subunit of P-like fimbriae) expression by Crp was demonstrated using a reporter assay and DNase I footprinting. Moreover, the pmpA/crp double mutant exhibited reduced kidney adhesion comparable to that of the pmpA mutant, and mouse kidney colonization by the pmpA mutant was significantly attenuated. Hence, the upregulation of P-like fimbriae in the crp mutant substantially enhanced kidney colonization. Moreover, increased survival in macrophages, increased stress tolerance, RpoS upregulation, and flagellum deficiency leading to immune evasion may promote kidney colonization by the crp mutant. This is the first study to elucidate the role of Crp in the virulence of uropathogenic P. mirabilis, underlying mechanisms, and related therapeutic potential.
- Subjects :
- Adaptation, Biological
Animals
Binding Sites
Cell Line
Cell Survival
Cyclic AMP Receptor Protein genetics
Diabetes Mellitus, Experimental
Disease Models, Animal
Gene Expression Regulation, Bacterial
Glucose metabolism
Humans
Macrophages immunology
Macrophages metabolism
Macrophages microbiology
Mice
Mutation
Protein Binding
Proteus Infections immunology
Bacterial Adhesion
Cyclic AMP Receptor Protein metabolism
Fimbriae, Bacterial physiology
Proteus Infections metabolism
Proteus Infections microbiology
Proteus mirabilis physiology
Stress, Physiological
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 7
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 28779108
- Full Text :
- https://doi.org/10.1038/s41598-017-07304-7