An Overview of Two-Component Signal Transduction Systems Implicated in Extra-Intestinal Pathogenic E. coli Infections

Abstract

Extra-intestinal pathogenic E. coli (ExPEC) infections are common in mammals and birds. The predominant ExPEC types are avian pathogenic E. coli (APEC), neonatal meningitis causing E. coli/meningitis associated E. coli (NMEC/MAEC), and uropathogenic E. coli (UPEC). Many reviews have described current knowledge on ExPEC infection strategies and virulence factors, especially for UPEC. However, surprisingly little has been reported on the regulatory modules that have been identified as critical in ExPEC pathogenesis. Two-component systems (TCSs) comprise the predominant method by which bacteria respond to changing environments and play significant roles in modulating bacterial fitness in diverse niches. Recent studies have highlighted the potential of manipulating signal transduction systems as a means to chemically re-wire bacterial pathogens, thereby reducing selective pressure and avoiding the emergence of antibiotic resistance. This review begins by providing a brief introduction to characterized infection strategies and common virulence factors among APEC, NMEC, and UPEC and continues with a comprehensive overview of two-component signal transduction networks that have been shown to influence ExPEC pathogenesis.

A Novel PhoP/PhoQ Regulation Pathway Modulates the Survival of Extraintestinal Pathogenic Escherichia coli in Macrophages

“…Sensing the environmental stimuli and undertaking adaptive change are crucial for ExPEC pathogenesis. Pathogens exploit two-component systems (TCSs) in response to the host environments during their infection ( 29 ). The comparative genomic analysis shows that about 62 TCSs genes are conserved in E. coli genomes.…”

“…The comparative genomic analysis shows that about 62 TCSs genes are conserved in E. coli genomes. However, there are little studies on the roles of TCSs in ExPEC pathogenesis ( 29 ). The PhoP/PhoQ, a typical TCS, is broadly conserved in Gram-negative bacteria; it can sense host intracellular signals and regulate bacterial adaptive lifestyle change during its infection ( 30 , 31 ).…”

Interaction of lipoprotein QseG with sensor kinase QseE in the periplasm controls the phosphorylation state of the two-component system QseE/QseF in Escherichia coli

“…As a common theme, deletion mutants of the qseEGF operon are attenuated in virulence, as demonstrated for Citrobacter rodentium , the fish pathogen Edwardsiella tarda , enterohemorrhagic Escherichia coli (EHEC), Salmonella enterica and Yersinia pseudotuberculosis [ 21 – 25 ]. This phenomenon has been studied most thoroughly in EHEC, in which QseE/QseF together with the QseB/QseC TCS complexly regulate virulence genes encoded within and outside of the locus of enterocyte effacement (LEE), a pathogenicity island organized in 5 operons (for recent reviews, see: [ 26 – 28 ]). Regulation by QseE/QseF is indirect and occurs through GlmY/GlmZ, which promote translation of virulence gene espFU and selectively destabilize transcripts of the LEE4 and 5 operons [ 29 ].…”

TheEscherichia coliCpxAR system does not sense surface contact

“…Our results indicate that RcsCDB, but not CpxAR, is activated upon attachment. Thus, the role of E. coli's Cpx system as a surface sensing system, as widely assumed (2,4,5,(30)(31)(32)(33), needs to be reconsidered.…”