Bacterial Quorum-Sensing Systems and Their Role in Intestinal Bacteria-Host Crosstalk

Abstract

Quorum-sensing (QS) system is a rapidly developing field in which we are gradually expanding our understanding about how bacteria communicate with each other and regulate their activities in bacterial sociality. In addition to collectively modifying bacterial behavior, QS-related autoinducers may also be embedded in the crosstalk between host and parasitic microbes. In this review, we summarize current studies on QS in the intestinal microbiome field and its potential role in maintaining homeostasis under physiological conditions. Additionally, we outline the canonical autoinducers and their related QS signal-response systems by which several pathogens interact with the host under pathological conditions, with the goal of better understanding intestinal bacterial sociality and facilitating novel antimicrobial therapeutic strategies.

Keywords: autoinducers; bacterial communication; host cells; metabolites; quorum sensing.

FIGURE 1

Five main signaling molecules in QS system. HSL, homoserine lactone; SAM, S-adenosylmethionine; AHL, acyl-homoserine lactones; AIP, autoinducing Peptides; NprB, neutral protease B; Opp, oligopeptide permease system; AI, autoinducer; DPD, 4,5-dihydroxy-2,3-pentanedione; Tdh, threonine dehydrogenase; Epi, epinephrine; NE, norepinephrine; Trp, tryptophan; Tna, tryptophanase. Detailed information can be found in section “Classical QS in Bacterial Communication.”

FIGURE 2

Intestinal bacterial distribution and QS signals. In the ileum (small intestine), Lactobacillus and Proteobacteria are the most abundant bacteria. E. coli, which belongs to Proteobacteria, communicates with other bacteria via AI-2, Indole and AHL signals. In cecum crypts, Firmicutes including Clostridium, Lactobacillus, Enterococcus, Proteobacteria, and Actinobacteria can be found. AIP, AHL, Indole, AI-2 and AI-3 may all exist in this region. At the distal end of the proximal colon, a thin but dense band called interlaced layer separates bacteria from epithelium. The interlaced layer of proximal colon is dominated by Lachnospiraceae and Ruminococcaceae. From transverse colon to rectum, mucus increases and divides into two layers. Firmicutes, Bacteroidetes, Actinobacteria, proteobacteria, and Verrucomicrobia live in the loose mucus layer.

FIGURE 3

QS maybe involved in communication between intestinal bacteria and host cells under physiological or pathological conditions. In the physiological state, several QS signal molecules are implicated in the crosstalk between host cell and parasitic bacteria. AI-2 activates the NF-κB signaling pathway in IEC cells to upregulate the level of cytokine IL-8. AI-2 promotes TNFSF9 gene expression in macrophages. 3-oxo-C12:2 (AHLs) decreases IL-8 secretion in IL-1β-stimulated IECs. Indole enhances the epithelial barrier function via activating pregnane X receptor (PXR) and aryl hydrocarbon receptor (AHR). Meanwhile, IECs produce AI-2 mimic signals that can be recognized by AI-2 receptor, and regulate QS related genes expression in bacteria. Under pathological states, for example, Clostridium difficile infection, indole-producing bacteria sense QS signals and create a unique environment with high levels of indole, which inhibits common intestinal bacteria recovery and benefits C. difficile self-survival. “lactic acid bacteria” (LAB) such as Bifidobacterium can inhibit enterohemorrhagic Escherichia coli (EHEC) virulence by AI-2 signals. Ruminococcus. obeum restricts Vibrio cholerae colonization through AI-2 signals.