Quorum sensing dependent phenotypes and their molecular mechanisms in Campylobacterales

Abstract

Quorum sensing comprises the mechanism of communication between numerous bacteria via small signalling molecules, termed autoinducers (AI). Using quorum sensing, bacteria can regulate the expression of multiple genes involved in virulence, toxin production, motility, chemotaxis and biofilm formation, thus contributing to adaptation as well as colonisation. The current understanding of the role of quorum sensing in the lifecycle of Campylobacterales is still incomplete. Campylobacterales belong to the class of Epsilonproteobacteria representing a physiologically and ecologically diverse group of bacteria that are rather distinct from the more commonly studied Proteobacteria, such as Escherichia and Salmonella. This review summarises the recent knowledge on distribution and production of AI molecules, as well as possible quorum sensing dependent regulation in the mostly investigated species within the Campylobacterales group: Campylobacter jejuni and Helicobacter pylori.

Keywords: AI-2; Campylobacter; Helicobacter; LuxS; quorum sensing.

Fig. 1.

Mechanism of AI-1 mediated signalling in V. fisheri. The AI-1 synthase LuxI produces AI-1 signalling molecules which can diffuse across the cell wall. The complex of AI-1 molecules with the intracellular receptor LuxR functions as transcriptional activator of the lux-operon resulting in enhanced expression of luxI and other genes necessary for production of bioluminescence.

Fig. 2.

Mechanism of AI-2 mediated signalling in V. harveyi and E. coli. The AI-2 signalling molecules are synthesised by the enzyme LuxS and exported to the environment. Two different mechanisms are described for the signal transduction. In V. harveyi, AI-2 binds to the LuxP receptor protein, thereby inducing a phosphorylation-dependent signalling cascade of LuxQ, LuxU and LuxO. Dephosphorylated LuxO enhances protein synthesis of the transcriptional activator LuxR, which results in increased expression of the lux-operon. The import of AI-2 molecules by the ABC-transporter (composed of LsrA, LsrB and LsrC) in E. coli results in phosphorylation of the signalling molecules by LsrK. Phosphorylated AI-2 inactivates LsrR (transcriptional repressor) and thereby increases the expression of the lsr-operon and can modulate the transcription of other target genes. LsrG, LsrF and LsrE are able to dephosphorylate AI-2.

Fig. 3.

Metabolic function of LuxS. Methionine recycling, methylation of DNA and proteins as well asde novocysteine synthesis is affected by the ACM. The SAM-synthetase MetK converts methionine to S-adenosylmethione (SAM). The cleavage of methyl residues from SAM results in the formation of S-adenosylhomocysteine (SAH), which can be converted to homocysteine either in a one- or two-step reaction. The SAH-hydrolase metabolises SAH to adenosine and homocysteine in a one-step reaction. In the other pathway, Pfs cleaves SAH into adenine and S-ribosylhomocysteine (SRH), which in turn is cleaved into 4,5-dihydroxyl-2,3-pentanedione (DPD) and homocysteine by LuxS. Homocysteine can be converted to methionine by the methyltransferase (MetE or MetH) or to cystathione and further cysteine by the enzymes CysK and MetB.

Fig. 4.

Dendrogram of LuxS and localisation of the luxS gene in Campylobacterales. Cluster analysis was done with Bionumerics v6.2 by pairwise alignment and UPGMA. If more than one LuxS sequence was available for a species, the consensus sequence was determined with Bionumerics; otherwise, the strain name is declared. All analysed sequences are listed in Table 1. Numbers indicate the percentage of similarity. Species in blue belong to the family of Campylobacteraceae and red to Helicobacteraceae. The up- and down-stream located genes of luxS in the analysed species are shown on the right-hand side of the dendrogram. Genes not annotated so far are coloured in grey. Gene name or function of the encoded proteins is mentioned within the arrows. A. (Arcobacter), C. (Campylobacter), H. (Helicobacter), S. (Sulfuricurvum), Su. (Sulfurimonas), Sul. (Sulfospirillum), W. (Wolinella).

Fig. 5.

Alignment of LuxS from Campylobacterales. LuxS sequences were aligned by the multiple sequence alignment with hierarchical clustering (Multalin software) [25]. The green boxes indicate the catalytically active site (H-X-X-E-H) and G92 which is important for LuxS activity. The strains are listed in Table 1. Consensus levels: high = 90% are shown in red and low = 50% are shown in blue. Consensus symbols: “!” is anyone of IV, “$” is anyone of LM, “%” is anyone of FY, “#” is anyone of NDQEBZ.