Modulation of AggR levels reveals features of virulence regulation in enteroaggregative E. coli

Abstract

Enteroaggregative Escherichia coli (EAEC) strains are one of the diarrheagenic pathotypes. EAEC strains harbor a virulence plasmid (pAA2) that encodes, among other virulence determinants, the aggR gene. The expression of the AggR protein leads to the expression of several virulence determinants in both plasmids and chromosomes. In this work, we describe a novel mechanism that influences AggR expression. Because of the absence of a Rho-independent terminator in the 3′UTR, aggR transcripts extend far beyond the aggR ORF. These transcripts are prone to PNPase-mediated degradation. Structural alterations in the 3′UTR result in increased aggR transcript stability, leading to increased AggR levels. We therefore investigated the effect of increased AggR levels on EAEC virulence. Upon finding the previously described AggR-dependent virulence factors, we detected novel AggR-regulated genes that may play relevant roles in EAEC virulence. Mutants exhibiting high AggR levels because of structural alterations in the aggR 3′UTR show increased mobility and increased pAA2 conjugation frequency. Furthermore, among the genes exhibiting increased fold change values, we could identify those of metabolic pathways that promote increased degradation of arginine, fatty acids and gamma-aminobutyric acid (GABA), respectively. In this paper, we discuss how the AggR-dependent increase in specific metabolic pathways activity may contribute to EAEC virulence.

Nutritional, molecular, and functional properties of a novel enzymatically hydrolyzed porcine plasma product

“…Intestinal infection with E. coli. To induce the intestinal infection, cimetidine (50 mg/kg; Sigma-Aldrich, St. Louis, MI, USA) was administrated intraperitoneally on day 30 of age and, 3 h later, E. coli strain 042 was inoculated by oral gavage as previously described [35]. Nonchallenged mice received vehicle.…”

The synergistic interaction of systemic inflammation, dysbiosis and antimicrobial resistance promotes growth restriction in children with acute severe malnutrition: An emphasis on Escherichia coli

“…Plausibly, gene enrichment is determined by genome architecture; however, the outcome is also responsive to environmental cues. For instance, whereas aggR, a major regulator of EAEC virulence -and also the most associated factor to environmental enteric dysfunction and linear growth (Das et al, 2021), induces expression of virulence genes in response to oxygen concentration, it also causes a metabolic shift over gut and enhances transmission of virulence plasmids (Prieto et al, 2021). Speculatively, coupled regulation of aggR and N-HS (a thermoregulator silencer of AT rich or foreign DNA) via aar might have consequences beyond attachment timing; after all, H-NS regulates the expression of multidrug exporter genes (Nishino and Yamaguchi, 2004), and since plasmids coding H-NS like proteins as in IncX3 bearing Bla-NDM1, it improves plasmid stability and virulence (Liu et al, 2020).…”

A Novel Adult Murine Model of Typical Enteroaggregative Escherichia coli Infection Reveals Microbiota Dysbiosis, Mucus Secretion, and AAF/II-Mediated Expression and Localization of β-Catenin and Expression of MUC1 in Ileum

“…AggR is a member of the AraC/XylS family of bacterial transcriptional activators that control the expression of a plethora of virulence factors; in strain 042, it is encoded on both the bacterial chromosome and the EAEC-specific aggregative adherence plasmid (pAA) ( Estrada-Garcia and Navarro-Garcia, 2012 ). AggR activates the expression of factors important in colonization, such as dispersin (AAP), allowing EAEC strains to disperse through the mucus and reach the enterocyte surface, AAF variants I–V, which mediate adherence in vitro to human epithelial cells and probably promote intestinal colonization, and the Aai-type VI secretion system ( Dudley et al., 2006 ), important in bacterial pathogenesis ( Jønsson et al., 2017 ; Navarro-Garcia et al., 2019 ; Prieto et al., 2021 ). In addition, tEAEC has a variable number of SPATEs (serine protease autotransporters of Enterobacteriaceae), including Pic (a protein involved in intestinal colonization), which is involved in colonization and hypersecretion of mucus, a hallmark of EAEC pathogenesis ( Navarro-Garcia et al., 2010 ).…”