- Please check and comment entries here.
Myxobacteria are Gram-negative δ-proteobacteria found predominantly in terrestrial habitats and often brightly colored due to the biosynthesis of carotenoids. Carotenoids are lipophilic isoprenoid pigments that protect cells from damage and death by quenching highly reactive and toxic oxidative species, like singlet oxygen, generated upon growth under light. The model myxobacterium Myxococcus xanthus turns from yellow in the dark to red upon exposure to light because of the photoinduction of carotenoid biosynthesis. How light is sensed and transduced to bring about regulated carotenogenesis in order to combat photooxidative stress has been extensively investigated in M. xanthus using genetic, biochemical and high-resolution structural methods. These studies have unearthed new paradigms in bacterial light sensing, signal transduction and gene regulation, and have led to the discovery of prototypical members of widely distributed protein families with novel functions. Major advances have been made in elucidating the molecular mechanisms underlying the light-dependent signaling and regulation of the transcriptional response leading to carotenogenesis in M. xanthus.
2. Conclusions and implications
Delving into how M. xanthus “sees” and mounts a photooxidative stress response that triggers carotenogenesis uncovered two novel pathways and with them new paradigms in bacterial light sensing, signal transduction and gene regulation, as well as the discovery of prototypical members of widely distributed protein families with novel functions. One pathway relies on a form of vitamin B12 and its association with a single photoreceptor-cum-transcriptional factor, and the other is a B12-independent, more complex route that requires various singular factors. Many worthy firsts can be credited to elucidation of the two pathways. This includes discovery of one of the first ECF-σ factors, CarQ; the founding members of the large protein family of B12-based CarH photoreceptors that occur in bacteria; the founding members of the CarD_CdnL family of bacterial RNA polymerase-binding transcription factors that are widely distributed in bacteria and occur in M. xanthus and other δ-proteobacteria, α-proteobacteria, Actinomycetes, Firmicutes, Deinococcus-Thermus and Spirochaetes, but not in β-, γ- or ε-proteobacteria, Chlamydiae or Cyanobacteria; the long-sought human desaturase involved in plasmalogen biosynthesis through its M. xanthus homolog. Insights specific to M. xanthus and closely related bacteria, but also ones more broadly conserved across bacteria, have emerged. This photooxidative stress response is linked, directly or indirectly, to responses to copper, to heme and fatty acid biosynthesis, and shares global regulators with processes as diverse as fruiting body development and activation of CRISPR-Cas systems. Future work will undoubtedly reveal new, possibly surprising, interconnections to other cellular activities.
Beyond bacterial physiology, signaling and gene regulation, the findings from M. xanthus light-induced carotenogenesis have had other important ramifications. How this response and its unique factors are conserved across bacteria and other organisms provides valuable evolutionary insights, especially since it involves some factors that are more typical of eukaryotes than other bacteria. Indeed, one hypothesis for the origin of eukaryotes known as the Syntrophy hypothesis posits that an ancestral early myxobacterial-like deltaproteobacterium may have participated in the symbiosis or syntrophy that produced the first eukaryotic cell because of the many eukaryotic-like genes in myxobacteria like M. xanthus. For example, the study of M. xanthus light-induced carotenogenesis has led to the discovery of a human/animal lipid desaturases essential in plasmalogen synthesis. This not only revealed a remarkable conservation of this enzyme across a vast evolutionary distance, but also has important implications in human health and disease, since plasmalogens have been linked to various human disorders including cancer and Alhzeimer´s disease. Knowing the identity of this long-sought desaturase helps to directly assess the role of plasmalogens in diverse pathologies, and has already proved useful in studies of mitochondrial metabolism and ferroptosis. Satisfyingly, CarH has now been exploited as one of the few green-light responsive optogenetic tools for light-controlled gene expression in M. xanthus and transgene expression in mammalian and plant cells; in receptor interactions and signaling in human cells and zebra fish embryos; in the generation of protein hydrogels for facile encapsulation and release of cells and proteins, and in cell adhesions that have been adapted to address challenges in regenerative neurobiology for sustained delivery of neuroprotective cytokines aimed at neuronal survival and axon regeneration in vivo.
The entry is from 10.3390/microorganisms9051067
- S. Padmanabhan; Antonio Monera-Girona; Ricardo Pérez-Castaño; Eva Bastida-Martínez; Elena Pajares-Martínez; Diego Bernal-Bernal; María Galbis-Martínez; María Polanco; Antonio Iniesta; Marta Fontes; et al. Light-Triggered Carotenogenesis in Myxococcus xanthus: New Paradigms in Photosensory Signaling, Transduction and Gene Regulation. Microorganisms 2021, 9, 1067, 10.3390/microorganisms9051067.