CAMP receptor protein regulates mouse colonization, motility, fimbria-mediated adhesion, and stress tolerance in uropathogenic Proteus mirabilis
Journal
Scientific Reports
Journal Volume
7
Journal Issue
1
Pages
7282
Date Issued
2017
Author(s)
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. ? 2017 The Author(s).
SDGs
Other Subjects
cyclic AMP binding protein; glucose; protein binding; adaptation; animal; bacterium adherence; binding site; cell line; cell survival; disease model; experimental diabetes mellitus; fimbria; gene expression regulation; genetics; human; immunology; macrophage; metabolism; microbiology; mouse; mutation; physiological stress; physiology; Proteus infection; Proteus mirabilis; Adaptation, Biological; Animals; Bacterial Adhesion; Binding Sites; Cell Line; Cell Survival; Cyclic AMP Receptor Protein; Diabetes Mellitus, Experimental; Disease Models, Animal; Fimbriae, Bacterial; Gene Expression Regulation, Bacterial; Glucose; Humans; Macrophages; Mice; Mutation; Protein Binding; Proteus Infections; Proteus mirabilis; Stress, Physiological
Type
journal article