Intestinal bacteria employ microbial metabolites from the microbiota and chemical signaling during cell-to-cell communication to regulate several cellular functions. Pathogenic bacteria are extremely efficient in orchestrating their response to these signals through complex signaling transduction systems. Precise coordination and interpretation of these multiple chemical cues is important within the gastrointestinal (GI) tract. Enteric foodborne pathogens, such as enterohemorrhagic Escherichia coli (EHEC) and Salmonella enterica serovar Typhimurium, or the surrogate murine infection model for EHEC, Citrobacter rodentium, are all examples of microorganisms that modulate the expression of their virulence repertoire in response to signals from the microbiota or the host, such as autoinducer-3 (AI-3), epinephrine (Epi), and norepinephrine (NE). The QseBC and QseEF two-component systems, shared by these pathogens, are involved in sensing these signals. We review how these signaling systems sense and relay these signals to drive bacterial gene expression; specifically, to modulate virulence. We also review how bacteria chat via chemical signals integrated with metabolite recognition and utilization to promote successful associations among enteric pathogens, the microbiota, and the host. KEYWORDS chemical signaling, Enterobacteriaceae, Escherichia, Salmonella, intestinal metabolites COMMENSALS AND PATHOGENS IN THE GUTT he large and diverse bacterial community in the human gut also has important functions in the physiology of the intestine. The intestinal mucosa forms a physical barrier that keeps the microbiota on the luminal side. The mucus layer is composed of mucin, glycoproteins, trefoil peptides, and surfactant phospholipids (Fig. 1). Altogether, they constitute a nutrient-rich mucus layer, which has an important role as a protective barrier against microorganisms (1). The biogeography of the gastrointestinal (GI) tract is diverse in its composition and density and its distinct chemical and physical features (2). The density and composition of bacterial communities change according to their location in the gut. Throughout the GI tract, there is significant variation in the physicochemical conditions and substrate availability that impact bacterial growth, differentially promoting or hampering the colonization of certain niches by various species. In the proximal colon, the high concentration of sugar substrates in the mucus allows the expansion of the saccharolytic members of the microbiota (Table 1). Inversely, the lower availability of sugar substrates in the distal colon triggers proteolysis, which decreases the bacterial growth rate and the diversity of the microbiota (1, 3). The resident microbiota, together with all chemical and physical features of the intestine, contribute to shape the metabolic landscape within the gut, producing a multitude of characterized and as-yet-unknown intestinal metabolites. Moreover, the microbial composition of the human GI tract varies with age, diet, host genetics, a...

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Enteroaggregative Escherichia coli (EAEC) from the O104:H4 specific serotype caused a large outbreak of bloody diarrhea with some complicated cases of hemolytic-uremic syndrome (HUS) in Europe in 2011. The outbreak strain consisted in an EAEC capable to produce the Shiga toxin (Stx) subtype 2a, a characteristic from enterohemorrhagic E. coli. QseBC two-component system detects AI-3/Epi/NE and mediates the chemical signaling between pathogen and mammalian host. This system coordinates a cascade of virulence genes expression in important human enteropathogens. The blocking of QseC of EAEC C227-11 (Stx+) strain by N-phenyl-4-{[(phenylamino) thioxomethyl]amino}-benzenesulfonamide (also known as LED209) in vivo demonstrated a lower efficiency of colonization. The periplasmic protein VisP, which is related to survival mechanisms in a colitis model of infection, bacterial membrane maintenance, and stress resistance, here presented high levels of expression during the initial infection within the host. Under acid stress conditions, visP expression levels were differentiated in an Stx-dependent way. Together, these results emphasize the important role of VisP and the histidine kinase sensor QseC in the C227-11 (Stx+) outbreak strain for the establishment of the infectious niche process in the C57BL/6 mouse model and of LED209 as a promising antivirulence drug strategy against these enteric pathogens. IMPORTANCE EAEC is a remarkable etiologic agent of acute and persistent diarrhea worldwide. The isolates harbor specific subsets of virulence genes and their pathogenesis needs to be better understood. Chemical signaling via histidine kinase sensor QseC has been shown as a potential target to elucidate the orchestration of the regulatory cascade of virulence factors.