Are There Acyl-Homoserine Lactones within Mammalian Intestines?

Abstract

Many Proteobacteria are capable of quorum sensing using N-acyl-homoserine lactone (acyl-HSL) signaling molecules that are synthesized by LuxI or LuxM homologs and detected by transcription factors of the LuxR family. Most quorum-sensing species have at least one LuxR and one LuxI homolog. However, members of the Escherichia, Salmonella, Klebsiella, and Enterobacter genera possess only a single LuxR homolog, SdiA, and no acyl-HSL synthase. The most obvious hypothesis is that these organisms are eavesdropping on acyl-HSL production within the complex microbial communities of the mammalian intestinal tract. However, there is currently no evidence of acyl-HSLs being produced within normal intestinal communities. A few intestinal pathogens, including Yersinia enterocolitica, do produce acyl-HSLs, and Salmonella can detect them during infection. Therefore, a more refined hypothesis is that SdiA orthologs are used for eavesdropping on other quorum-sensing pathogens in the host. However, the lack of acyl-HSL signaling among the normal intestinal residents is a surprising finding given the complexity of intestinal communities. In this review, we examine the evidence for and against the possibility of acyl-HSL signaling molecules in the mammalian intestine and discuss the possibility that related signaling molecules might be present and awaiting discovery.

Core Principles of Bacterial Autoinducer Systems

“…This has consequences for the estimation of the relevance of signaling within the population but also for the impact of AIs on other bacteria or host cells. This may (partly) explain the conflicting findings that AIs are central regulators of virulence in most pathogens and that some AIs directly affect host cells in vitro but that most studies detect little or no AI in samples of lung, sputum, gut, and others (146). Mixing events before or during sampling may further destroy spatial structure.…”

The Interplay between the Microbiota and Enterohemorrhagic Escherichia coli

“…In support of this notion, AHLs have been found within the rumen contents of cattle fed both grain and forage diets (86,90,91). However, chemical analysis of lower GI tract contents from cattle and nonruminant animals has not revealed the presence of AHLs, which may be due to inadequate sensitivity of the methods used, alkaline instability of AHLs, or potentially the existence of exotic homoserine lactones or non-AHL small molecules that may influence SdiA function (40).…”

“…The AI-3 QS signaling system intersects with the host adrenergic signaling system (epinephrine/norepinephrine [NE] hormones) (40). In fact, this intersection occurs at a biochemical level, with the same bacterial receptor, the membrane-bound histidine sensor kinase (HK) QseC, sensing the bacterial signal AI-3 and the host signals epinephrine and/or NE (41).…”

“…Supernatants of EHEC grown to late exponential phase contain a signal capable of inducing transcription of many EHEC virulence genes, including the locus of enterocyte effacement (LEE) that encodes a type III secretion system (T3SS) essential for EHEC to attach to and efface enterocytes and promote disease (37,38), the flagellum regulon, and expression of Shiga toxin (35,39). Purified and synthetic AI-2 was unable to govern LEE and flagella expression (40), suggesting the existence of an additional class of autoinducer (AI-3). The identity of AI-3 is not yet known, but it is methanol soluble (35), likely tyrosine derived (36), and shares signaling mechanisms with host-derived epinephrine and norepinephrine (Fig.…”

“…The AI-3/epinephrine/NE interkingdom signaling cascade activates expression of virulence genes in EHEC (39,40,46,47). The host hormones epinephrine/NE are specifically sensed by two HKs: QseC and QseE, which are the first bacterial adrenergic receptors identified (46,48).…”