A LuxS-Dependent Cell-to-Cell Language Regulates Social Behavior and Development inBacillus subtilis

Abstract

Cell-to-cell communication in bacteria is mediated by quorum-sensing systems (QSS) that produce chemical signal molecules called autoinducers (AI).In particular, LuxS/AI-2-dependent QSS has been proposed to act as a universal lexicon that mediates intra-and interspecific bacterial behavior. Here we report that the model organism Bacillus subtilis operates a luxS-dependent QSS that regulates its morphogenesis and social behavior. We demonstrated that B. subtilis luxS is a growth-phase-regulated gene that produces active AI-2 able to mediate the interspecific activation of light production in Vibrio harveyi. We demonstrated that in B. subtilis, luxS expression was under the control of a novel AI-2-dependent negative regulatory feedback loop that indicated an important role for AI-2 as a signaling molecule. Even though luxS did not affect spore development, AI-2 production was negatively regulated by the master regulatory proteins of pluricellular behavior, SinR and Spo0A. Interestingly, wild B. subtilis cells, from the undomesticated and probiotic B. subtilis natto strain, required the LuxS-dependent QSS to form robust and differentiated biofilms and also to swarm on solid surfaces. Furthermore, LuxS activity was required for the formation of sophisticated aerial colonies that behaved as giant fruiting bodies where AI-2 production and spore morphogenesis were spatially regulated at different sites of the developing colony. We proposed that LuxS/AI-2 constitutes a novel form of quorumsensing regulation where AI-2 behaves as a morphogen-like molecule that coordinates the social and pluricellular behavior of B. subtilis.Bacteria not only behave as self-sufficient individuals but also act as communities capable of cell-cell communication (7,15,20,42,53). This social interaction leads to the coordination of communitarian activities that resemble, in their complexity, the behaviors observed in multicellular organisms (20,42,49,53,57). This microbial phenomenon is known as quorum sensing, a process by which bacteria monitor their cell population density by measuring the concentration of small secreted signal molecules called autoinducers (57). Even though a vast number of diverse quorum-sensing systems exist (41, 46, 57), they can be divided into two established paradigms that regulate the intraspecific behavior in many bacteria: (i) LuxI/LuxR-type quorum-sensing systems in gram-negative bacteria responsible for the production of N-acyl-L-homoserine lactone autoinducers or type I autoinducers and (ii) oligopeptide/two component-type quorum-sensing circuits in gram-positive bacteria responsible for the production of autoinducer peptides (4,17,26,32,44).However, in recent years, a considerable amount of information has been gained on the existence of another type of quorum-sensing system that not only seems to participate in intraspecific bacterial behavior but also seems to regulate the interspecific interactions among bacteria of different genera. This system involves the production of autoinducer-2 (AI-2) signal molecul...

Diversity and functional analysis of luxS genes in Vibrios from marine sponges Mycale laxissima and Ircinia strobilina

“…luxS genes are highly divergent among gram-negative and gram-positive bacteria but might have similar functions. For example, the luxS gene of Bacillus subtilis shares only ca 40% identity to that of V. cholerae and V. harveyi; however, AI-2 produced in B. subtilis can induce the bioluminescence of V. harveyi BB170 and LuxS-dependent QS is required to form a differentiated biofilm and also for swarming on solid surfaces (Lombardia et al, 2006). Further, even among the vibrios, the luxS gene of V. cholerae shares only 87% identity to that of V. harveyi yet the lux operon of V. harveyi can function well in V. cholerae (Lenz et al, 2004).…”

Thinking about Bacillus subtilis as a multicellular organism

“…Different isolates obtained from the environment as well as different strains used in industry, such as B. subtilis natto (extensively used in Japan for the production of a food product derived from fermented soybeans), display a wide range of colony morphologies [17]. It is likely that variations in gene content as well as differences in the regulatory circuits involved account for the distinct phenotypes observed.…”

“…Among these are CcpA [32] and LuxS [17]. However, whether they feed into the SinR-dependent pathway regulating matrix synthesis remains unknown.…”

Escherichia coli transcription factor YncC (McbR) regulates colanic acid and biofilm formation by repressing expression of periplasmic protein YbiM (McbA)

“…LuxS converts S-ribosyl-homocysteine into homocysteine and 4,5-dihydroxy-2,3-pentanedione (DPD), which cyclizes spontaneously into a family of AI-2 molecules (Lombardia et al, 2006). As a bacterial communication signal, AI-2 is exported by TqsA (Herzberg et al, 2006) and internalized by a lsr operon-encoded system (Taga et al, 2003), and then controls a variety of genes (DeLisa et al, 2001b;Xavier and Bassler, 2003;Ren et al, 2004b).…”