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Streptomyces, Molecular Biology of

Encyclopedia of Molecular Cell Biology and Molecular Medicine2006

Paul Herron, Emma Tilley, Iain S. Hunter

Abstract

Streptomyces are mycelial, soil-dwelling, differentiating bacteria that are renowned for the production of many clinically-useful antibiotics (e.g. streptomycin, erythromycin, tetracyclines, and a number of the third-generation penicillin-like antibiotics). They also make other useful metabolites (e.g. anticancer agents, immunosuppressants, antihelmintics, growth promoters, herbicides, and insecticides). Their status as simple microbial models of differentiation is well established and, because they are taxonomically related to pathogens such as mycobacteria that cause tuberculosis and leprosy (but are themselves "safe" organisms), they are being cited increasingly as informative models for these life-threatening pathogens. Much effort has gone into investigating the fundamental biology of Streptomyces . In recent years, the dissection of the architecture and regulation of antibiotic production gene clusters has been undertaken, together with studies on the regulatory circuits that control production and integrate with the signaling pathways of the differentiation processes. As clinical infections invariably develop resistance to antibiotics, there is an ongoing need to discover new drugs to combat this problem. The Streptomyces are viewed as a rich source of such drugs and contemporary effort, using recombinant technologies, is aimed at altering the genes for antibiotic production pathways so that they produce new, potentially useful metabolites that may keep them one step ahead of the resistance problem. Recent advances in the molecular biological techniques applicable to streptomycetes have assisted greatly in this task. The genome sequence of the model streptomycete, Streptomyces coelicolor , was published in 2002, followed recently by that of Streptomyces avermitilis . In 2004, a number of other sequencing projects were in progress, so that these resources will grow significantly in the near future. The Streptomyces are remarkable in that their genomes are among the largest (8–9 Mb, compared with E. coli at 4.6 Mb) reported so far for any bacteria. Bioinformatics, combined with postgenomic techniques such as microarrays and proteome gels, are now being used to define and characterize global gene expression under a variety of conditions. Rapid methods have been developed to create mutants for any gene, using its genome-derived DNA sequence to guide the strategy. Mutant libraries generated by random transposon insertion, are also becoming available. These aim to provide a collection of mutants in which each of the almost 8000 genes in Streptomyces is mutated individually. With these recent postgenomic resources building on the robust genetic systems that have been set up for Streptomyces , the next few years promise to be an exciting phase in our understanding of these unique bacteria.

Abstract

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