Cell-cell interactions

Abstract

All Gram-negative and Gram-positive bacteria that swarm differentiate elongated, hyper-flagellated, rod-shaped cells. Bacteria that lack flagella and cannot swim in liquid can nevertheless generate compact, organized, highly dynamic swarms on agar surfaces. Typically, these bacteria grow as elongated rods and they have polar engines, such as retractile type IV pili or other gliding engines to propel themselves over a moist surface. Myxobacteria are, perhaps, the best-studied non-flagellated swarmers. They are among the most socially adept and ubiquitous of bacteria that live in cultivated soil. They feed as an organized multicellular swarm on a wide variety of other soil bacteria. A feeding swarm spreads outward, forming regular multicellular structures as it expands. Shortly before potential prey have been completely consumed in their neighborhood, a swarm ceases growth with expansion and builds multilayered fruiting bodies with dormant spores. Both swarming/growth and starvation-induced fruiting body development depend upon the specificity and effectiveness of signals passed between cells. Some signals are small, diffusible molecules like a set of amino acids for the A-signal; others are particular proteins displayed on the surface of the outer membrane like the C-signal. A proposed signal that would be essential for the formation of multicellular rafts and multilayered mounds consists of contact junctions between pairs of cells that persist for a rather short time before disconnecting. When consumption outruns the available food supply, cells change their behavior: The swarm stops outward expansion and retreats, migrating inward to build hundreds of fruiting bodies, each containing about 105 spores. Sensing a deficiency of any amino-acylated tRNA, the swarm initiates its program of fruiting body development. For development, the swarm allocates some remaining resources to DNA synthesis in order that each spore will contain two complete copies of the genome. Energy reserves are also allocated to developmental protein synthesis. Myxococcus xanthus uses the stringent response to initiate a cascade of enhancer-binding proteins (EBPs) that organizes smooth transitions from exponential growth to preaggregation and then to mound building. EBPs are specific transcriptional activators that work with sigma-54-RNA polymerase to activate transcription at designated sigma-54 promoters. Expression of a downstream EBP is activated at the proper time by a preceding EBP in the cascade, ensuring the correct developmental order. Since EBPs typically activate gene expression in response to an environmental cue, it is thought that several of the cascade's sensor kinases measure the level of particular intermediary metabolites indicative of approaching starvation. Early detection of starvation's approach seems to limit spore formation because only 0.1-1% of the cells initiating fruiting body development become spores. Two EBPs initiate accumulation of the ppGpp starvation signal to manage the transition from growth to fruiting body development. Two other EBPs manage the subsequent preaggregation stage, while another two regulate gene expression for cell aggregation. The A-signal indicates that there are enough cells to build a fruiting body; the C-signal directs fruiting body construction and sets the time at which each motile rod-shaped cell becomes a spherical, nonmotile spore that is resistant to solar radiation. Later, when fresh prey bacteria return to the neighborhood of a fruiting body, the myxospores germinate, and the cells begin to elongate to feed on the new prey. M. xanthus assembles a new swarm that expands because cells reverse their gliding direction every 8-9 min, determined by a pacemaking oscillator. The pacemaker, in turn, drives a G-protein switch that coordinately exchanges the A- and the S-engines to opposite cell poles, and reverses the direction of gliding. Periodic reversals help the cells build multicellular structures of 102-103 cells. The ability of growing swarms of M. xanthus to build mounds is used by starving cells to build their large, mounded fruiting bodies. At each stage, building multicellular structures to precise specifications relies on the signals passed between cells.