Actinobacteria are Gram-positive bacteria with high G+C DNA content that constitute one of the largest bacterial phyla, and they are ubiquitously distributed in both aquatic and terrestrial ecosystems. Many Actinobacteria have a mycelial lifestyle and undergo complex morphological differentiation. They also have an extensive secondary metabolism and produce about two-thirds of all naturally derived antibiotics in current clinical use, as well as many anticancer, anthelmintic, and antifungal compounds. Consequently, these bacteria are of major importance for biotechnology, medicine, and agriculture. Actinobacteria play diverse roles in their associations with various higher organisms, since their members have adopted different lifestyles, and the phylum includes pathogens (notably, species of Corynebacterium, Mycobacterium, Nocardia, Propionibacterium, and Tropheryma), soil inhabitants (e.g., Micromonospora and Streptomyces species), plant commensals (e.g., Frankia spp.), and gastrointestinal commensals (Bifidobacterium spp.). Actinobacteria also play an important role as symbionts and as pathogens in plant-associated microbial communities. This review presents an update on the biology of this important bacterial phylum.

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Taxonomy, Physiology, and Natural Products of Actinobacteria

The genus Mycobacterium is best known for its two major pathogenic species, M. tuberculosis and M. leprae, the causative agents of two of the world's oldest diseases, tuberculosis and leprosy, respectively. M. tuberculosis kills approximately two million people each year and is thought to latently infect one-third of the world's population. One of the most remarkable features of the nonsporulating M. tuberculosis is its ability to remain dormant within an individual for decades before reactivating into active tuberculosis. Thus, control of cell division is a critical part of the disease. The mycobacterial cell wall has unique characteristics and is impermeable to a number of compounds, a feature in part responsible for inherent resistance to numerous drugs. The complexity of the cell wall represents a challenge to the organism, requiring specialized mechanisms to allow cell division to occur. Besides these mycobacterial specializations, all bacteria face some common challenges when they divide. First, they must maintain their normal architecture during and after cell division. In the case of mycobacteria, that means synthesizing the many layers of complex cell wall and maintaining their rod shape. Second, they need to coordinate synthesis and breakdown of cell wall components to maintain integrity throughout division. Finally, they need to regulate cell division in response to environmental stimuli. Here we discuss these challenges and the mechanisms that mycobacteria employ to meet them. Because these organisms are difficult to study, in many cases we extrapolate from information known for gram-negative bacteria or more closely related GC-rich gram-positive organisms.

Bacterial Growth and Cell Division: a Mycobacterial Perspective

The use of mutants and molecular genetics has begun to reveal how differentiation is brought about in multicellular, mycelial Streptomyces spp. Alternative pathways to aerial mycelium formation may be activated on different media. In some cases, extracellular signals are transmitted or exchanged. Extracellular proteins may act as morphogens in the erection of aerial hyphae. A rare codon, UUA, is apparently confined to mRNAs from a few genes important only for early stages of differentiation; it is absent from vegetative or developmentally late mRNAs. Sporulation of aerial hyphae involves at least four specific regulatory proteins, including a sigma factor and an unusual small protein. A complex interplay between the sporulation regulatory genes, rather than a simple linear dependence cascade, is emerging.

Genetics of differentiation in Streptomyces.

As an undergraduate at Cambridge in the early 1950s, I had found genetics the most exciting part of my courses. This was the main motivation for choosing Botany as my Part II (final year) option in the academic year 1953}54. Granted, there was the Department of Genetics at Cambridge, headed by none other than Ronald Fisher, the father of biological statistics and a true genius, but an advanced qualification in mathematics was a de facto entry ticket to Part II Genetics, reflecting the strong mathematical basis of research in that Department. In the Botany School, ‘biochemical genetics ’ was being studied – using Neurospora crassa – by Harold Whitehouse and Lewis Frost. During the Part II course in Botany, they far-sightedly emphasized the power and promise of microbial genetics for the future understanding of gene structure and function. In choosing a PhD project to start in October 1954 I heeded their advice. One of the topics on offer was Streptomyces. Here was a group of microbes apparently ‘ intermediate between bacteria and fungi ’, and so they could not fail to be interesting from a genetic point of view, given the clear differences that were emerging between the genetics of the few bacteria so far studied and the genetics of fungi and higher organisms. In the Pneumococcus, Escherichia coli and Salmonella typhimurium, incomplete genomes were transferred from donor to recipient strains, by any of three bizarre processes (transformation, conjugation and transduction), to yield incomplete zygotes, whereas in fungi and higher organisms (except those that were asexual) life cycles, including a complete diploid stage and meiosis, were the rule.

Forty years of genetics with Streptomyces: from in vivo through in vitro to in silico.

Streptomyces coelicolor is the genetically best characterized species of a populous genus belonging to the gram-positive Actinobacteria. Streptomycetes are filamentous soil organisms, well known for the production of a plethora of biologically active secondary metabolic compounds. The Streptomyces developmental life cycle is uniquely complex and involves coordinated multicellular development with both physiological and morphological differentiation of several cell types, culminating in the production of secondary metabolites and dispersal of mature spores. This review presents a current appreciation of the signaling mechanisms used to orchestrate the decision to undergo morphological differentiation, and the regulators and regulatory networks that direct the intriguing development of multigenomic hyphae first to form specialized aerial hyphae and then to convert them into chains of dormant spores. This current view of S. coelicolor development is destined for rapid evolution as data from -omics studies shed light on gene regulatory networks, new genetic screens identify hitherto unknown players, and the resolution of our insights into the underlying cell biological processes steadily improve. (Less)

Signals and regulators that govern Streptomyces development

SUMMARY: Fifty whi mutants of Streptomyces coelicolor, having white instead of the wild-type grey colonies, were examined microscopically and genetically. The aerial mycelium structure of the mutants was broadly classified into six types, ranging from the complete absence of any stage of sporulation to the presence of apparently normal spores. Eight map locations were discovered for whi genes, all in previously well-marked regions of the map. Closely linked mutations possessed similar aerial mycelium structure, with few exceptions.

K. F. Chater

Papers

A morphological and genetic mapping study of white colony mutants of Streptomyces coelicolor.