Ultrasensitive Response of Developing Myxococcus xanthus to the Addition of Nutrient Medium Correlates with the Level of MrpC

Abstract

Upon depletion of nutrients, forms mounds on a solid surface. The differentiation of rod-shaped cells into stress-resistant spores within mounds creates mature fruiting bodies. The developmental process can be perturbed by the addition of nutrient medium before the critical period of commitment to spore formation. The response was investigated by adding a 2-fold dilution series of nutrient medium to starving cells. An ultrasensitive response was observed, as indicated by a steep increase in the spore number after the addition of 12.5% versus 25% nutrient medium. The level of MrpC, which is a key transcription factor in the gene regulatory network, correlated with the spore number after nutrient medium addition. The MrpC level decreased markedly by 3 h after adding nutrient medium but recovered more after the addition of 12.5% than after 25% nutrient medium addition. The difference in MrpC levels was greatest midway during the period of commitment to sporulation, and mound formation was restored after 12.5% nutrient medium addition but not after adding 25% nutrient medium. Although the number of spores formed after 12.5% nutrient medium addition was almost normal, the transcript levels of "late" genes in the regulatory network failed to rise normally during the commitment period. However, at later times, expression from a reporter gene fused to a late promoter was higher after adding 12.5% than after adding 25% nutrient medium, consistent with the spore numbers. The results suggest that a threshold level of MrpC must be achieved in order for mounds to persist and for cells within to differentiate into spores. Many signaling and gene regulatory networks convert graded stimuli into all-or-none switch-like responses. Such ultrasensitivity can produce bistability in cell populations, leading to different cell fates and enhancing survival. We discovered an ultrasensitive response of to nutrient medium addition during development. A small change in nutrient medium concentration caused a profound change in the developmental process. The level of the transcription factor MrpC correlated with multicellular mound formation and differentiation into spores. A threshold level of MrpC is proposed to be necessary to initiate mound formation and create a positive feedback loop that may explain the ultrasensitive response. Understanding how this biological switch operates will provide a paradigm for the broadly important topic of cellular behavior in microbial communities.

Transcriptomic analysis of the Myxococcus xanthus FruA regulon, and comparative developmental transcriptomic analysis of two fruiting body forming species, Myxococcus xanthus and Myxococcus stipitatus

“…Nonetheless, these data suggest a potential new paradigm for FruA’s activity in regulating fruiting body formation. It is generally assumed that FruA is activated by MrpC to aid in activating the developmental pathway, and recent work suggests that MrpC is transcribed proportionally to nutrient availability [ 57 ]. In contrast, these results suggest that FruA could have an additional role.…”

An amino‐terminal threonine/serine motif is necessary for activity of the Crp/Fnr homolog, MrpC and forMyxococcus xanthusdevelopmental robustness

“…Multiple signaling systems feed into MrpC (Nariya and Inouye, ; Stein et al , ; Higgs et al , ; Inouye and Nariya, ; Schramm et al , ; Rajagopalan and Kroos, ; Hoang and Kroos, ), and MrpC directly and indirectly induces regulatory feedback loops (Kroos, ; Hoang and Kroos, ). Threshold levels of MrpC induce aggregation and sporulation, and misaccumulation of MrpC can lead to inappropriate cell fate segregation (Cho and Zusman, ; Schramm et al , ; Rajagopalan and Kroos, ; Kroos, ; Hoang and Kroos, ). It is likely that these regulatory systems integrate to control MrpC accumulation and thus tune the developmental program to the variable environmental conditions that M. xanthus encounters in the wild.…”

“…MrpC is positioned as a hub in the genetic regulatory network controlling M. xanthus development. Multiple signaling systems feed into MrpC (Nariya and Inouye, ; Stein et al , ; Higgs et al , ; Inouye and Nariya, ; Schramm et al , ; Rajagopalan and Kroos, ; Hoang and Kroos, ), and MrpC directly and indirectly induces regulatory feedback loops (Kroos, ; Hoang and Kroos, ). Threshold levels of MrpC induce aggregation and sporulation, and misaccumulation of MrpC can lead to inappropriate cell fate segregation (Cho and Zusman, ; Schramm et al , ; Rajagopalan and Kroos, ; Kroos, ; Hoang and Kroos, ).…”

Regulation of late-acting operons by three transcription factors and a CRISPR-Cas component duringMyxococcus xanthusdevelopment

“…Nutrients and an unknown signal sensed by the Esp system stimulate proteolysis of MrpC (Fig. 11) to delay or halt development (36)(37)(38)(39). The presumed advantage of such a developmental checkpoint is to ensure that cellular physiology and interactions with other cells, as well as environmental conditions, warrant commitment to spore formation (38,76,77).…”