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Review
. 2018 Dec;110(6):863-878.
doi: 10.1111/mmi.14127. Epub 2018 Nov 1.

Social behaviours by Bacillus subtilis: quorum sensing, kin discrimination and beyond

Margarita Kalamara  1 , Mihael Spacapan  2 , Ines Mandic-Mulec  2 , Nicola R Stanley-Wall  1
Affiliations
Review

Social behaviours by Bacillus subtilis: quorum sensing, kin discrimination and beyond

Margarita Kalamara et al. Mol Microbiol. 2018 Dec.

Abstract

Here, we review the multiple mechanisms that the Gram-positive bacterium Bacillus subtilis uses to allow it to communicate between cells and establish community structures. The modes of action that are used are highly varied and include routes that sense pheromone levels during quorum sensing and control gene regulation, the intimate coupling of cells via nanotubes to share cytoplasmic contents, and long-range electrical signalling to couple metabolic processes both within and between biofilms. We explore the ability of B. subtilis to detect 'kin' (and 'cheater cells') by looking at the mechanisms used to potentially ensure beneficial sharing (or limit exploitation) of extracellular 'public goods'. Finally, reflecting on the array of methods that a single bacterium has at its disposal to ensure maximal benefit for its progeny, we highlight that a large future challenge will be integrating how these systems interact in mixed-species communities.

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Figures

Figure 1
Figure 1
Multicellular behaviours exhibited by B. subtilis. Biofilm formation, assessed after growth on MSgg agar and imaged 48 h after growth at 30°C (top left) [method from (Branda et al., 2001)]. Protease secretion tested on LB+ 1% milk (w/v) agar plates. The image was taken 18 h after growth at 37°C (top right) [method from (Verhamme et al., 2007)]. Swarming motility assessed on low salt LB agar + 0.7% agar (w/v) plates and imaged 8 h after incubation at 37°C (bottom left) [method from (Kearns and Losick, 2003)]. Sliding motility tested by growth on MsggN plates for 72 h at 37°C (bottom right) [method from (Fall et al., 2006)]. In each case, the B. subtilis undomesticated isolate NCIB 3610 was used.
Figure 2
Figure 2
The ComXQPA quorum sensing system in Bacillus subtilis. Illustration of the function of the ComXQPA system in B. subtilis under low (A) and high (B) cell density conditions. Dashed arrows represent indirect regulation. Pre‐ComX (chain of circles) is synthesised in the cell, modified and exported by ComQ, resulting in secretion of the ComX pheromone (single circle). ComP is the ComX receptor. In low cell density conditions, the extracellular concentration of ComX is low and ComP does not bind ComX. Under high cell density conditions, however, the extracellular concentration of ComX increases and ComX binds ComP. ComP phosphorylates and activates ComA. ComA~P subsequently facilitates surfactin production and activates the production of DegQ. DegQ indirectly controls the phosphorylation and activation of DegU, leading to production and secretion of exoproteases. Secretion of surfactin indirectly causes phosphorylation of Spo0A and Spo0A~P facilitates production of the extracellular matrix.
Figure 3
Figure 3
The ComXQPA and Rap/Phr quorum sensing systems in Bacillus subtilis. Schematic of the quorum sensing systems under low (A) and high (B) cell density conditions. Pre‐Pro‐Phr is synthesised in the cytoplasm. The signal peptide (represented in brown circles) is cleaved off and Pro‐Phr is secreted and modified in the extracellular environment to produce the Phr peptide (light green circle). Under low cell density conditions, the extracellular concentrations of Phr are low and Phr does not enter the cell. The Rap protein represses the response regulators ComA~P, DegU~P and indirectly Spo0A~P. Under high cell density conditions, the extracellular concentration of Phr increases and the Phr peptide enter the cells through the Opp system. Phr represses Rap allowing ComA~P, DegU~P and Spo0A~P to facilitate the production of public goods.
Figure 4
Figure 4
Quorum sensing and cheating. Schematic of the effect that acquisition of an additional Rap/Phr system has in Bacillus subtilis cheating. A. Representation of the parental strain, which encodes for the Com system and a single Rap/Phr system. The cell produces ComX pheromones and Phr peptides. B. The ‘Extra‐Rap’ strain, which has the same Com and Rap/Phr system as the parental strain plus an additional Rap/Phr (Rap2/Phr2, shown in blue) system. C. When the parental strain is at a quorum and the ‘Extra‐Rap’ strain is at a low density in the population, the extracellular concentrations of ComX and Phr are high, while Phr2 is present at low concentrations in the extracellular environment. ComX and Phr enter all cells (both the parental and ‘Extra‐Rap’). ComX leads to phosphorylation of ComA and Phr represses Rap. In the parental strain, ComA is free to facilitate public good production; while, in the ‘Extra‐Rap’ system, the absence of intracellular Phr2 results in a Rap2 repressing ComA~P, thereby repressing public good production. D. When both the parental strain and the ‘Extra‐Rap’ strain are at a quorum, public goods are produced by the parental strain as described in C). In the ‘Extra‐Rap’ strain, increased extracellular concentration of Phr2 results in the peptide entering the cell and repressing Rap2, allowing a contribution to public good production.
Figure 5
Figure 5
Kin discrimination in B. subtilis. A. Different phenotypes of approaching B. subtilis swarms can be used to distinguish kin and non‐kin strains of B. subtilis. Merging swarms indicate kin (two B strains) and a striking boundary indicates non‐kin swarms (strain A and strain B) (Stefanic et al., 2015); B. Phylogenetic tree adapted from Lyons and Kolter, 2017. The tree was calculated using the 16S rRNA sequence of a reference strain of each indicated species. The number of isolates of each species used in the study is indicated in parentheses. The separate clades are marked beside the tree and the purple gradient represents the cut‐off point for kin discrimination against Bacillus subtilis NCIB 3610.
Figure 6
Figure 6
Long‐range and contact‐dependent communication in B. subtilis. A. Long‐range metabolic signalling occurs in developing biofilm communities and results in oscillations between growth and growth inhibition. B. Contact‐dependent communication between B. subtilis and other cells (either B. subtilis or other species) occurs using nanotubes. Cytoplasmic contents can be moved from donor to recipient cells, while small nutrient molecules can be extracted from the prey cell by the predator, demonstrating bidirectional movement of molecules.
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