Myxococcus xanthus Developmental Cell Fate Production: Heterogeneous Accumulation of Developmental Regulatory Proteins and Reexamination of the Role of MazF in Developmental Lysis

Abstract

Myxococcus xanthus undergoes a starvation-induced multicellular developmental program during which cells partition into three known fates: (i) aggregation into fruiting bodies followed by differentiation into spores, (ii) lysis, or (iii) differentiation into nonaggregating persister-like cells, termed peripheral rods. As a first step to characterize cell fate segregation, we enumerated total, aggregating, and nonaggregating cells throughout the developmental program. We demonstrate that both cell lysis and cell aggregation begin with similar timing at approximately 24 h after induction of development. Examination of several known regulatory proteins in the separated aggregated and nonaggregated cell fractions revealed previously unknown heterogeneity in the accumulation patterns of proteins involved in type IV pilus (T4P)-mediated motility (PilC and PilA) and regulation of development (MrpC, FruA, and C-signal). As part of our characterization of the cell lysis fate, we set out to investigate the unorthodox MazF-MrpC toxin-antitoxin system which was previously proposed to induce programmed cell death (PCD). We demonstrate that deletion of mazF in two different wild-type M. xanthus laboratory strains does not significantly reduce developmental cell lysis, suggesting that MazF's role in promoting PCD is an adaption to the mutant background strain used previously.

Division of Labor in Biofilms: the Ecology of Cell Differentiation

“…Historically, cell lysis was proposed to provide nutrients that allow spore differentiation. In addition, more recent results suggest that cell lysis may also play a role in the aggregation of cells (73,78).…”

“…Since cell lysis in stalk cells is under regulatory control (78,86), the behavior of stalk cells cannot be explained by local adaptation. Instead, cell lysis is expected to yield benefits at the colony level, much like the lysis of vegetative mycelium in Streptomyces discussed above.…”

“…Sporulation only occurs within fruiting bodies, and cells that will sporulate differentially express certain genes required for sporulation (77) and show different protein profiles than nonsporulating cells, termed "peripheral rods" (73,78). Peripheral rods are a discrete subpopulation of cells that remain outside of the fruiting bodies.…”

The predatory life cycle of Myxococcus xanthus

“…xanthus and Bac. subtilis demonstrate autolytic and cannibalistic activity, respectively, under certain lab conditions (Lee et al, 2012;Berleman et al, 2006;Shank et al, 2011), although there is evidence that both species prefer predation to lysis (Berleman et al, 2006;Nandy et al, 2007). Indeed, it seems likely that within microbial communities of mixed species, cannibalism may only occur under extreme Model for contact-dependent mechanism of prey-cell lysis.…”

Post-Segregational Killing, Altruistic Cell Death, and Other Toxin/Antitoxin Fallacies

“…For example, although roughly 80% of vegetative Myxococcus xanthus cells undergo PCD during nutrient-limiting development (one of the few examples of bacterial PCD), it was claimed that MazF mediated this killing (Nariya and Inouye, 2008). However, this result was later shown to be an artifact of a defect in the PilQ1 secretin of this strain used in the initial report by two different groups 75 (Lee, et al, 2012, Boynton, et al, 2013. Hence, PCD does not occur for wild-type M. xanthus trains through MazF.…”