Dual Biochemical Oscillators May Control Cellular Reversals in Myxococcus xanthus

Abstract

Myxococcus xanthus is a Gram-negative, soil-dwelling bacterium that glides on surfaces, reversing direction approximately once every 6 min. Motility in M. xanthus is governed by the Che-like Frz pathway and the Ras-like Mgl pathway, which together cause the cell to oscillate back and forth. Previously, Igoshin et al. (2004) suggested that the cellular oscillations are caused by cyclic changes in concentration of active Frz proteins that govern motility. In this study, we present a computational model that integrates both the Frz and Mgl pathways, and whose downstream components can be read as motor activity governing cellular reversals. This model faithfully reproduces wildtype and mutant behaviors by simulating individual protein knockouts. In addition, the model can be used to examine the impact of contact stimuli on cellular reversals. The basic model construction relies on the presence of two nested feedback circuits, which prompted us to reexamine the behavior of M. xanthus cells. We performed experiments to test the model, and this cell analysis challenges previous assumptions of 30 to 60 min reversal periods in frzCD, frzF, frzE, and frzZ mutants. We demonstrate that this average reversal period is an artifact of the method employed to record reversal data, and that in the absence of signal from the Frz pathway, Mgl components can occasionally reverse the cell near wildtype periodicity, but frz- cells are otherwise in a long nonoscillating state.

The predatory life cycle of Myxococcus xanthus

“…On a molecular level, cell reversals are triggered by a pole-to-pole change in motility proteins, such as FrzZ, MglB and MglA, which then causes the Myx. xanthus cell to reverse direction (Eckhert et al, 2014;Kaimer & Zusman, 2013;Keilberg & Søgaard-Andersen, 2014). …”

Bacteria that Glide with Helical Tracks

“…Cells may gain some control of their movements by breaking free of this rigid oscillation. A model that might explain how this could occur exploits the similarity between the chemotactic signal transduction (Che) system that controls the direction of rotation of the bacterial flagellar motor and the Frz signaling system in myxobacteria that controls cell reversal frequency [28]. …”

Allosteric regulation of a prokaryotic small Ras-like GTPase contributes to cell polarity oscillations in bacterial motility

“…xanthus changes its direction of movement by swapping the leading and lagging poles. The reversal frequency is regulated by the chemosensory-like frizzy (Frz) pathway, which relays environmental signals to the downstream MglA-MglB polarity control system [11–13] (Fig 1). High-resolution time-lapse experiments revealed that MglA and MglB relocalize sequentially during a reversal [4,7,11].…”

“…It was recently shown that RomR and its interacting partner RomX are essential for recruiting MglA-GTP to the poles [16]. Frz-signaling and RomR stimulates the pole-to-pole exchange of MglA and MglB [11,13–15]. All together, these proteins form a so-called gated relaxation oscillator, which functions to drive the polarity reversals in response to environmental signals [11].…”