The soil-dwelling, filamentous bacteria of the genus Streptomyces are renowned for their production of useful secondary metabolites including antibiotics. The work described in this thesis provides... Show moreThe soil-dwelling, filamentous bacteria of the genus Streptomyces are renowned for their production of useful secondary metabolites including antibiotics. The work described in this thesis provides new insights on the role and regulation of antibiotic production and resistance in these bacteria. It shows that antibiotic resistance is already beneficial at sub-inhibitory antibiotic concentrations. Resistance can even readily evolve at such low concentrations, thereby possibly explaining the level of resistance seen in pristine environments. Antibiotic producers can benefit from spatial structure, as present in the soil, through the preferential allocation of resources and this enables invasion from low frequencies. Streptomyces do not produce all antibiotics continuously, but antibiotic production is instead tightly regulated in response to environmental cues, including those produced by competitors. Streptomyces are most likely to induce antibiotic production in response to a competitor that shares similar secondary metabolite clusters, indicating a possible role for shared signalling. Besides changes in antibiotic production, other responses to competition are revealed on a transcriptomic level, including an increased expression of developmental genes, suggesting earlier sporulation. Show less
Streptomyces are multicellular, Gram-positive bacteria in the phylum of actinobacteria which produce a high amount of bioactive natural products of which the expression is tightly coordinated with... Show moreStreptomyces are multicellular, Gram-positive bacteria in the phylum of actinobacteria which produce a high amount of bioactive natural products of which the expression is tightly coordinated with the life cycle. This thesis shows the identification of S. roseifaciens, a novel species with an uncommon, verticillate spore morphology and a unique household of SsgA-like proteins. Analyses of the peptidoglycan composition show that S. coelicolor show a pattern of 3-3 cross-linking befitting a tip-growing organism and change in composition between vegetative mycelium and spores. Kitasatosporae carry meso-DAP in the peptidoglycan of vegetative mycelium and LL-DAP in the peptidoglycan of spores. In line with this difference, the peptidoglycan architecture of these two growth stages undergoes such radical changes that they would seem to be from different species. S. coelicolor is naturally vancomycin resistant, but the addition of D-alanine and disruption in a single gene increases vancomycin sensitivity by a thousandfold. A knockout mutant of the alanine racemase, alr, requires exogenous addition of D-alanine. The Alr crystal structure of S. coelicolor and the D-cycloserine producer S. lavendulae were compared as to look for possible mechanisms for D-cycloserine resistance. Show less
