Myxococcus xanthus Swarms Are Driven by Growth and Regulated by a Pacemaker

Abstract

The principal social activity of Myxococcus xanthus is to organize a dynamic multicellular structure, known as a swarm. Although its cell density is high, the swarm can grow and expand rapidly. Within the swarm, the individual rod-shaped cells are constantly moving, transiently interacting with one another, and independently reversing their gliding direction. Periodic reversal is, in fact, essential for creating a swarm, and the reversal frequency controls the rate of swarm expansion. Chemotaxis toward nutrient has been thought to drive swarming, but here the nature of swarm growth and the impact of genetic deletions of members of the Frz family of proteins suggest otherwise. We find that three cytoplasmic Frz proteins, FrzCD, FrzF, and FrzE, constitute a cyclic pathway that sets the reversal frequency. Within each cell these three proteins appear to be connected in a negative-feedback loop that produces oscillations whose frequencies are finely tuned by methylation and by phosphorylation. This oscillator, in turn, drives MglAB, a small G-protein switch, to oscillate between its GTP-and GDP-bound states that ultimately determine when the cell moves forward or backward. The periodic reversal of interacting rod-shaped cells promotes their alignment. Swarm organization ensures that each cell can move without blocking the movement of others.For many years myxobacterial swarming has been viewed as a chemotactic process in which swarm cells are attracted to greener pastures beyond the swarm edge (9,25,34,40). Also, Myxococcus xanthus is said to be attracted to prey bacteria when it forms concentric ripples that advance toward the prey (1), but how ripples imply chemotaxis has not been explained. Investigating chemotaxis in M. xanthus, a Gram-negative deltaproteobacterium, has been motivated by the presence of six frizzy genes, five of which encode proteins with some similarity (28 to 40% identity at the amino acid level) to the core chemotaxis proteins found in Escherichia coli and Salmonella (2). Despite continuing attempts to identify chemotactic attractants, only phosphatidylethanolamine (PE), a normal constituent of M. xanthus membranes, has been found to increase the frequency of reversals of starved cells, a process called stimulation (18). Stimulation, however, does not depend on the frizzy proteins (23, 39). Since no methyl-accepting chemotaxis (MCP) protein receptor for PE has been identified, extracellular PE might instead be interacting with the cell's outer membrane and the largely unknown machinery that induces reversal of gliding direction. A serious molecular difficulty with the chemotactic view of M. xanthus behavior is that FrzCD, unlike the methyl-accepting chemotaxis proteins of E. coli, lacks both a transmembrane and an extracellular domain at its N terminus that would respond to attractant or repellant binding to a receptor. FrzCD is, moreover, localized to the cytoplasm (5, 24). The FrzE histidine kinase, like its E. coli homolog CheA, has no sensory domain and is also a cytoplasmic protein. FrzE...

Self-organization of bacterial biofilms is facilitated by extracellular DNA

“…3A, Fig. S4C) bear a striking resemblance to M. xanthus swarms cultured on the surface of solidified growth media (25).…”

Transmission of a signal that synchronizes cell movements in swarms of Myxococcus xanthus

“…(i) Swarms have flat tops; they are not heaped up like a colony. (ii) The rate at which a steady state swarm expands is directly proportional to the rate of individual cell movement, not to its rate of growth, and the increase in cell numbers contribute only 10% of the swarm expansion rate (5). All stages of growth can be found in a swarm.…”

“…Due to the way Myxococcus xanthus cells move and to the way cells interact with each other, their swarms spread outward (5). The capacity to spread arises from their ability to build different types of organized, dynamic, multicellular structures: planar, rectangular rafts of cells with their long axes aligned; and round multilayered mounds.…”

“…rate (5). The higher rate in a FrzG deletion could simply reflect a higher level of FrzCD methylation, resulting in unconstrained oscillation.…”

Cell Division Resets Polarity and Motility for the Bacterium Myxococcus xanthus

“…This suggests a layer of complexity in the associations of M. xanthus and other organisms that has not been considered previously-promotion of intercellular activity by neighboring cells can be both blocked and undone by predivision cells. Several studies have shown the importance of different biochemical and physical components that promote cell-cell interaction (11,18,21,22,44,(54)(55)(56), group alignment (21,44,56), and group motility (19,20,44,57,58) of M. xanthus. However, our results show that pausing for cell division dominates over any tested intercellular interactions, with no distinction between the pausing behavior of dividing cells that were in contact with other cells and that of dividing cells that were isolated.…”