PerC Manipulates Metabolism and Surface Antigens in Enteropathogenic Escherichia coli

Abstract

Enteropathogenic Escherichia coli is an important cause of profuse, watery diarrhea in infants living in developing regions of the world. Typical strains of EPEC (tEPEC) possess a virulence plasmid, while related clinical isolates that lack the pEAF plasmid are termed atypical EPEC (aEPEC). tEPEC and aEPEC tend to cause acute vs. more chronic type infections, respectively. The pEAF plasmid encodes an attachment factor as well as a regulatory operon, perABC. PerC, a poorly understood regulator, was previously shown to regulate expression of the type III secretion system through Ler. Here we elucidate the regulon of PerC using RNA sequencing analysis to better our understanding of the role of the pEAF in tEPEC infection. We demonstrate that PerC controls anaerobic metabolism by increasing expression of genes necessary for nitrate reduction. A tEPEC strain overexpressing PerC exhibited a growth advantage compared to a strain lacking this regulator, when grown anaerobically in the presence of nitrate, conditions mimicking the human intestine. We show that PerC strongly down-regulates type I fimbriae expression by manipulating fim phase variation. The quantities of a number of non-coding RNA molecules were altered by PerC. In sum, this protein controls niche adaptation, and could help to explain the function of the PerC homologs (Pch), many of which are encoded within prophages in related, Gram-negative pathogens.

A large self-transmissible plasmid from Nigeria confers resistance to multiple antibacterials without a carrying cost

“…PapB and PefB are prototypical members of a family of mobile element-borne fimbrial regulators (61) . They regulate core chromosomal adhesins in Escherichia (62,63). We cloned the pefB homolog under the control of the arabinose promoter to produce pRMPefB.…”

Self-Conjugation of the EnteropathogenicEscherichia coliAdherence Factor Plasmid of Four Typical EPEC Isolates

“…Future research will also be conducted to analyze the functional responses and gene expression profiles of these aEPEC pEAF-carrying strains, including the expression of BFP and the localized adherence phenotype, as well as the regulatory effect of the per locus over the LEE island. In this regard, recent global transcriptional analyses have demonstrated that pEAF genes influence the expression of a number of chromosomal genes in addition to the LEE [ 30 , 46 ].…”

Environment Controls LEE Regulation in Enteropathogenic Escherichia coli

“…Along with stimulating virulence gene expression, PerC regulates many genes. RNA-sequencing revealed that PerC regulates, either directly or indirectly, transcription of the fim operon, various metabolism genes, ribosomal RNAs, tRNAs, sRNAs, and others ( Mellies et al, 2017 ). PerC’s mechanism of action has remained largely elusive, but some observations are worth examining.…”

“…The intertwined regulation of these important players has implications in interpretation of their observed regulons. For instance, an increase in bfp transcripts in a ler mutant is likely due to decreased repression of perA , a known positive regulator of bfp ( Bustamante et al, 2011 ; Bingle et al, 2014 ; Mellies et al, 2017 ). Conversely, the fim operon was found to be increased in expression in both perC - and ler- deletion mutants.…”

“…Conversely, the fim operon was found to be increased in expression in both perC - and ler- deletion mutants. Down-regulation of fim by these regulators could possibly be explained by decreased fimE recombinase transcription, inverting the fimS element to the OFF orientation due to Ler in both cases ( Bingle et al, 2014 ; Mellies et al, 2017 ). The negative feedback loop between per and Ler dictates controlled regulation of the LEE, which is also coordinated by environmental signals.…”