Regulation of factors contributing to virulence in Escherichia coli

Abstract

Extraintestinal pathogenic strains of Escherichia coli cause a wide range of diseases including colibacillosis in chickens and urinary tract infections in humans. Persistent infections in E. coli and other gram-negative species are associated with population-dependent physiological processes such as cell-cell signaling and biofilm formation. Such social behaviors require careful coordination and modulation of gene expression in response to environmental cues. Adaptive response of bacteria in new environment is predominantly achieved through a signaling cascade called two-component regulatory systems. The function of the BarA/UvrY two-component regulatory system and its downstream factors in controlling virulence associated processes, specifically regulation of AI-2 based signaling and biofilm formation was investigated. In E. coli, a type of cell-cell signaling termed Quorum Sensing involves release, detection, and response to small molecule called autoinducer (AI-2), synthesis of which is dependent on luxS gene products via methyl cycle. The BarA-UvrY and Csr system displayed dual regulation on luxS expression at the level of transcription and post-transcription. The uptake of AI-2 by the Lsr transporter is also modulated by the signaling cascade suggested a balance between AI-2 synthesis and uptake in the cell. The role of transcriptional regulator uvrY in biofilm formation in Uropathogenic Escherichia coli was also studied. Mutation of uvrY reduced expression of fimA and papA, major fimbrial subunit of Type 1 and Pap pilus respectively. Acidic exopolysaccharide accumulation and the ability to swarm are also being impaired. Finally, uvrY mutants demonstrated poor colonization in kidneys and bladders in an ascending model of UTI. Overall, the effect of uvrY on biofilm formation seems to be multi-factorial and might play a critical role in adaptation and colonization of UPEC. The fine tuning of processes associated with cell-cell communication and biofilm formation at the level of transcription and post-transcription by the BarA/UvrY/CsrA signaling cascade indicated that this system might be crucial for quick adaptation, social behavior, colonization and virulence attributes in Escherichia coli.