A Vibrio cholerae autoinducer–receptor pair that controls biofilm formation

Abstract

SUMMARYQuorum sensing (QS) is a cell–cell communication process that enables bacteria to track cell population density and orchestrate collective behaviors. QS relies on production, detection, and response to extracellular signal molecules called autoinducers. In Vibrio cholerae, multiple QS circuits control pathogenesis and biofilm formation. Here, we identify and characterize a new QS autoinducer-receptor pair. The autoinducer is 3,5-dimethylpyrazin-2-ol, which we call DPO. DPO is made from threonine and alanine, and its synthesis depends on threonine dehydrogenase (Tdh). DPO binds to and activates a transcription factor, VqmA. The VqmA-DPO complex activates expression of vqmR, which encodes a small regulatory RNA. VqmR represses genes required for biofilm formation and toxin production. We propose that DPO allows V. cholerae to regulate collective behaviors to, among other possible roles, diversify its QS output during colonization of the human host.

Quorum Sensing Gene Regulation by LuxR/HapR Master Regulators in Vibrios

“…V. cholerae has four autoinducer receptors that feed into the same circuit to regulate HapR, one of which is unlike canonical Vibrio receptors in that it is not membrane bound (11)(12)(13). A new autoinducer-receptor pair was identified in V. cholerae; binding of the autoinducer 3,5-dimethylpyrazin-2-ol (DPO) is required for dimerization and function of the cytosolic transcription factor VqmA, which indirectly inhibits biofilm formation (51). The autoinducer-receptor systems in V. parahaemolyticus are likely similar to those in V. harveyi, based on phylogenetic analyses and signaling assays (10,14,16,42), whereas only the LuxPQ system that detects AI-2 has been identified in V. vulnificus (40).…”

A conserved RNA seed‐pairing domain directs small RNA‐mediated stress resistance in enterobacteria

“…Total RNA was prepared and blotted as described previously (Papenfort et al, 2017). Membranes (GE Healthcare Amersham) were hybridized with [ 32 P]-labeled DNA oligonucleotides at 42°C or 63°C when using riboprobes.…”

“…Experiments were performed as previously described (Papenfort et al, 2017). Briefly, total RNA was isolated using the SV Total RNA Isolation System (Promega), according to the manufacturer's instructions.…”

New Vocabulary for Bacterial Communication

“…[69] In addition to the two already known QS systems in V. cholerae,P apenfort et al recently discovered 3,5-dimethylpyrazin-2-one (DPO) as at hird autoinducer in V. cholerae. [70] DPO is sensed at ac ertain threshold by the LuxR solo VqmA through its PAS4 signal domain, which induces the expression of vqmR ( Figure 1B)t oregulate the pathogenicity of V. cholerae. [71] The first LuxR solo from Photorhabdus analysed in detail was PluR.…”