RESUMO
Two growth modes have been described for the filamentous Streptomyces bacteria. Their classic developmental life cycle culminates in the formation of dormant spores, where movement to new environments is mediated through spore dispersal. In contrast, exploratory growth proceeds as a rapidly expanding vegetative mycelium that leads to extensive surface colonization and is associated with the release of volatile compounds that promote alkalinization (and reduced iron bioavailability) of its surrounding environment. Here, we report that exploratory growth in Streptomyces venezuelae can proceed in tandem with classic sporulating development in response to specific nutritional cues. Sporulating exploration is not accompanied by a rise in environmental pH but has the same iron acquisition requirements as conventional exploration. We found that mutants that were defective in their ability to sporulate were unaffected in exploration, but mutants undergoing precocious sporulation were compromised in their exploratory growth and this appeared to be mediated through premature activation of the developmental regulator WhiI. Cell envelope integrity was also found to be critical for exploration, as mutations in the cell envelope stress-responsive extracytoplasmic function sigma factor SigE led to a failure to explore robustly under all exploration-promoting conditions. Finally, in expanding the known exploration-promoting conditions, we discovered that the model species Streptomyces lividans exhibited exploration capabilities, supporting the proposal that exploration is conserved across diverse streptomycetes. IMPORTANCE: Streptomyces bacteria have evolved diverse developmental and metabolic strategies to thrive in dynamic environmental niches. Here, we report the amalgamation of previously disparate developmental pathways, showing that colony expansion via exploration can proceed in tandem with colony sporulation. This developmental integration extends beyond phenotype to include shared genetic elements, with sporulation-specific repressors being required for successful exploration. Comparing this new exploration mode with previously identified strategies has revealed key differences (e.g., no need for environmental alkalinization), and simultaneously allowed us to define unifying requirements for Streptomyces exploration. The "reproductive exploration" phenomenon reported here represents a unique bet-hedging strategy, with the Streptomyces colony engaging in an aggressive colonization strategy while transporting a protected genetic repository.
Assuntos
Streptomyces , Animais , Streptomyces/metabolismo , Fatores de Transcrição/metabolismo , Ferro/metabolismo , Estágios do Ciclo de Vida , Esporos Bacterianos , Proteínas de Bactérias/metabolismoRESUMO
Streptomyces bacteria have been studied for more than 80 years thanks to their ability to produce an incredible array of antibiotics and other specialized metabolites and their unusual fungal-like development. Their antibiotic production capabilities have ensured continual interest from both academic and industrial sectors, while their developmental life cycle has provided investigators with unique opportunities to address fundamental questions relating to bacterial multicellular growth. Much of our understanding of the biology and metabolism of these fascinating bacteria, and many of the tools we use to manipulate these organisms, have stemmed from investigations using the model species Streptomyces coelicolor and Streptomyces venezuelae. Here, we explore the pioneering work in S. coelicolor that established foundational genetic principles relating to specialized metabolism and development, alongside the genomic and cell biology developments that led to the emergence of S. venezuelae as a new model system. We highlight key discoveries that have stemmed from studies of these two systems and discuss opportunities for future investigations that leverage the power and understanding provided by S. coelicolor and S. venezuelae.
Assuntos
Streptomyces coelicolor , Streptomyces , Antibacterianos/metabolismo , Streptomyces coelicolor/genética , Streptomyces/metabolismo , Proteínas de Bactérias/genéticaRESUMO
Exploration is a recently discovered mode of growth and behavior exhibited by some Streptomyces species that is distinct from their classical sporulating life cycle. While much has been uncovered regarding initiating environmental conditions and phenotypic outcomes of exploratory growth, how this process is coordinated at a genetic level remains unclear. We used RNA sequencing to survey global changes in the transcriptional profile of exploring cultures over time in the model organism Streptomyces venezuelae. Transcriptomic analyses revealed widespread changes in gene expression impacting diverse cellular functions. Investigations into differentially expressed regulatory elements revealed specific groups of regulatory factors to be impacted, including the expression of several extracytoplasmic function (ECF) sigma factors, second messenger signaling pathways, and members of the whiB-like (wbl) family of transcription factors. Dramatic changes were observed among primary metabolic pathways, especially among respiration-associated genes and the oxidative stress response; enzyme assays confirmed that exploring cultures exhibit an enhanced oxidative stress response compared with classically growing cultures. Changes in the expression of the glycerol catabolic genes in S. venezuelae led to the discovery that glycerol supplementation of the growth medium promotes a dramatic acceleration of exploration. This effect appears to be unique to glycerol as an alternative carbon source, and this response is broadly conserved across other exploration-competent species. IMPORTANCE Exploration represents an alternative growth strategy for Streptomyces bacteria and is initiated in response to other microbes or specific environmental conditions. Here, we show that entry into exploration involves comprehensive transcriptional reprogramming, with an emphasis on changes in primary metabolism and regulatory/signaling functions. Intriguingly, a number of transcription factor classes were downregulated upon entry into exploration. In contrast, respiration-associated genes were strongly induced, and this was accompanied by an enhanced oxidative stress response. Notably, our transcriptional analyses suggested that glycerol may play a role in exploration, and we found that glycerol supplementation dramatically enhanced the exploration response in many streptomycetes. This work sheds new light on the regulatory and metabolic cues that influence a fascinating new microbial behavior.
Assuntos
Glicerol , Streptomyces , Aceleração , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica , Glicerol/metabolismo , Estresse Oxidativo , Streptomyces/genética , Streptomyces/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
RNA metabolism is a critical but frequently overlooked control element affecting virtually every cellular process in bacteria. RNA processing and degradation is mediated by a suite of ribonucleases having distinct cleavage and substrate specificity. Here, we probe the role of two ribonucleases (RNase III and RNase J) in the emerging model system Streptomyces venezuelae. We show that each enzyme makes a unique contribution to the growth and development of S. venezuelae and further affects the secondary metabolism and antibiotic production of this bacterium. We demonstrate a connection between the action of these ribonucleases and translation, with both enzymes being required for the formation of functional ribosomes. RNase III mutants in particular fail to properly process 23S rRNA, form fewer 70S ribosomes, and show reduced translational processivity. The loss of either RNase III or RNase J additionally led to the appearance of a new ribosomal species (the 100S ribosome dimer) during exponential growth and dramatically sensitized these mutants to a range of antibiotics.