The RNA Chaperone Protein ProQ is a pleiotropic regulator in enteropathogenic Escherichia coli

Abstract

Enteropathogenic Escherichia coli (EPEC) is a gastrointestinal pathogen that affects individuals of all age groups, with infections ranging from subclinical colonization to acute or persistent diarrhea. The bacterium’s ability to cause diarrhea depends on the locus of enterocyte effacement (LEE) pathogenicity island. Although regulation of the LEE has been systematically characterized, until the last decade, these studies were limited to transcriptional control. Posttranscriptional regulation of the LEE is an underappreciated and understudied area of gene regulation. In the past few years, multiple reports have shed light on the roles of RNA-binding proteins, such as Hfq and CsrA, that modulate virulence in EPEC. This study was undertaken to explore the role of another RNA chaperone protein, ProQ, in the pathophysiology of EPEC. Our results suggest that deletion of proQ globally derepresses gene expression from the LEE in lysogeny broth (LB) suggesting that ProQ is a negative regulator of the LEE. Further interrogation of the role of ProQ in regulating the LEE-encoded type III secretion system revealed that ProQ globally silences the LEE by downregulating the expression of PerC – a prominent transcriptional activator of the LEE master regulator ler, which, in turn leads to the observed repression from the other LEE operons. Furthermore, ProQ appears to moonlight as it affects other physiological processes including type IV pili biogenesis, flagellar-motility, biofilm formation, tryptophan metabolism, and antibiotic resistance. Our study provides the very first evidence to implicate ProQ as a pleiotropic regulator in EPEC.