Understanding how bacteria talk to each other using autoinducer-2

Published in Microbiology
Understanding how bacteria talk to each other using autoinducer-2

Share this post

Choose a social network to share with, or copy the shortened URL to share elsewhere

This is a representation of how your post may appear on social media. The actual post will vary between social networks

In 1990s, Bonnie Bassler and colleagues1 discovered a quorum sensing signal called autoinducer-2 (AI-2), which is released by a large cohort of bacteria and has the capacity to mediate both intra- and interspecies communication. Despite the hypothesis that AI-2 is a kind of "bacterial esperanto"2, only two types of AI-2 receptors, LuxP and LsrB, have been identified to date in limited bacterial families. Whereas LuxP has been found exclusively in Vibrio spp., LsrB are present only in enteric bacteria and some members of the Rhizobiaceae, Bacillaceae and Clostridiaceae families, casting doubts on the universality of AI-2 signaling. Nevertheless, responses to AI-2, including changes in phenotypes and gene expression, have been widely detected in bacteria lacking LuxP- and LsrB-type receptors, strongly suggesting the existence of yet undiscovered receptors for this autoinducer. Earlier attempts to discover novel types of AI-2 receptors using either bioinformatics approaches or chemical probes were not successful3. We thus suspected that undiscovered AI-2 receptors might be evolutionally distinct from LuxP and LsrB. Using an alternative strategy, our new research identifies a third type of AI-2 receptor, consisting of a dCACHE domain.

The opportunistic pathogen Pseudomonas aeruginosa that do not code for LuxP- or LsrB-like AI-2 receptors have been shown to respond robustly to AI-2, leading to changes in gene expression and phenotypes such as biofilm formation and virulence production3,4. Although P. aeruginosa is a good model for studying previously unrecognized mechanisms of AI-2 perception, it was difficult for us to identify AI-2 receptors from biofilm- and virulence-related genes. Since AI-2 has been identified as the chemotactic signal involved in autoaggregation and biofilm formation in Escherichia coli5,6, we hypothesized that it might also induce chemotaxis in P. aeruginosa. Using chemotaxis assays, ITC experiments, biofilm formation assays and molecular docking analyses, our results suggest that AI-2 binds to the dCACHE domain of the chemoreceptors PctA and TlpQ of P. aeruginosa, thus inducing chemotaxis and biofilm formation. 

Given that the dCACHE domain is the most abundant family of extracytoplasmic sensors for all major types of signal transduction proteins in bacteria7, we next investigated whether other types of dCACHE-containing signal transduction proteins have the capacity to bind AI-2. To identify putative AI-2 sensors, 6 dCACHE domains structurally homologous to that of PctA were overexpressed, and we found AI-2 is also a ligand for the histidine kinase KinD from Bacillus subtilis and the diguanylate cyclase rpHK1S-Z16 from Rhodopseudomonas palustris (Figure 1). Using bioinformatics tools and in vitro experiments, our results further suggest that nearly 1500 dCACHE-containing signal transduction proteins predicted to function as methyl-accepting chemotaxis proteins, histidine kinases, c-di-GMP synthases and phosphodiesterases, serine phosphatases, serine/threonine kinases, adenylate- or guanylate cyclases from bacteria and archaea are potential AI-2 receptors. 

Figure 1. Model of perception of AI-2 by dCACHE-containing signal transduction proteins. AI-2 is detected by chemoreceptors PctA and TlpQ in P. aeruginosa, histidine kinase KinD in B. subtilis and c-di-GMP synthase rpHK1S-Z16 in R. palustris. Names of domains come from the Pfam database. Me, methyl group; P, phosphoryl group. MCPsignal, Methyl-accepting chemotaxis protein (MCP) signalling domain.

Our work provides important new insights into the mechanisms for the detection of and response to AI-2. These findings could help us to understand how AI-2 functions as a signal for intraspecies and interspecies communication in prokaryotes. Also, the identification of widely occurring AI-2 receptors paves the way for the manipulation of AI-2-mediated beneficial or hostile behaviors of polyspecies communities in niches of environmental or medical importance. 

The full paper (“Sensing of autoinducer-2 by functionally distinct receptors in prokaryotes”) is available at Nature Communications: https://www.nature.com/articles/s41467-020-19243-5

  1. Bassler, B. L., Greenberg, E. P. & Stevens, A. M.Cross-species induction of luminescence in the quorum-sensing bacterium Vibrio harveyi. Bacteriol. 179, 4043–4045 (1997).
  2. Winans, S. C. Bacterial esperanto. Struct. Biol.9, 83–84 (2002).
  3. Pereira, C. S., Thompson, J. A. & Xavier, K. B. AI-2-mediated signalling in bacteria. FEMS Microbiol. Rev.37, 156–181 (2013).
  4. Li, H. et al.Autoinducer-2 regulates Pseudomonas aeruginosa PAO1 biofilm formation and virulence production in a dose-dependent manner. BMC Microbiol. 15, 192 (2015).
  5. Bansal, T., Jesudhasan, P., Pillai, S., Wood, T. K. & Jayaraman, A. Temporal regulation of enterohemorrhagic Escherichia coli virulence mediated by autoinducer-2. Appl. Microbiol. Biotechnol. 78, 811–819 (2008).
  6. González Barrios, A. F. et al.Autoinducer 2 controls biofilm formation in Escherichia coli through a novel motility quorum-sensing regulator (MqsR, B3022). Bacteriol. 188, 305–316 (2006).
  7. Upadhyay, A. A., Fleetwood, A. D., Adebali, O., Finn, R. D. & Zhulin, I. B. Cache domains that are homologous to, but different from PAS domains comprise the largest superfamily of extracellular sensors in prokaryotes. PLoS Comput. Biol. 12, e1004862 (2016).


Please sign in or register for FREE

If you are a registered user on Research Communities by Springer Nature, please sign in

Subscribe to the Topic

Life Sciences > Biological Sciences > Microbiology

Related Collections

With collections, you can get published faster and increase your visibility.

Materials and devices for separation, sensing, and protection

In this Collection, the editors of Nature Communications and Communications Materials welcome the submission of primary research articles that highlight the development and application of functional materials in the areas of separation, sensing, and protection.

Publishing Model: Open Access

Deadline: Jun 30, 2024

Cancer and aging

This cross-journal Collection invites original research that explicitly explores the role of aging in cancer and vice versa, from the bench to the bedside.

Publishing Model: Hybrid

Deadline: Jul 31, 2024