Growth of desferrioxamine-deficient Streptomyces mutants through xenosiderophore piracy of airborne fungal contaminations.

Due to the necessity of iron for housekeeping functions, nutrition, morphogenesis and secondary metabolite production, siderophore piracy could be a key strategy in soil and substrate colonization by microorganisms. Here we report that mutants of bacterium Streptomyces coelicolor unable to produce desferrioxamine siderophores could recover growth when the plates were contaminated by indoor air spores of a Penicillium species and Engyodontium album. UPLC-ESI-MS analysis revealed that the HPLC fractions with the extracellular 'resuscitation' factors of the Penicillium isolate were only those that contained siderophores, i.e. Fe-dimerum acid, ferrichrome, fusarinine C and coprogen. The restored growth of the Streptomyces mutants devoid of desferrioxamine is most likely mediated through xenosiderophore uptake as the cultivability depends on the gene encoding the ABC-transporter-associated DesE siderophore-binding protein. That a filamentous fungus allows the growth of desferrioxamine non-producing Streptomyces in cocultures confirms that xenosiderophore piracy plays a vital role in nutritional interactions between these taxonomically unrelated filamentous microorganisms.

Altered desferrioxamine-mediated iron utilization is a common trait of bald mutants of Streptomyces coelicolor.

Streptomyces coelicolor is an important model organism for developmental studies of filamentous GC-rich actinobacteria. The genetic characterization of mutants of S. coelicolor blocked at the vegetative mycelium stage, the so-called bald (bld) mutants that are unable to erect spore-forming aerial hyphae, has opened the way to discovering the molecular basis of development in actinomycetes. Desferrioxamine (DFO) production and import of ferrioxamines (FO; iron-complexed DFO) are key to triggering morphogenesis of S. coelicolor and we show here that growth of S. coelicolor on the reference medium for Streptomyces developmental studies is fully dependent on DFO biosynthesis. UPLC-ESI-MS analysis revealed that all bld mutants tested are affected in DFO biosynthesis, with bldA, bldJ, and ptsH mutants severely impaired in DFO production, while bldF, bldK, crr and ptsI mutants overproduce DFO. Morphogenesis of bldK and bldJ mutants was recovered by supplying exogenous iron. Transcript analysis showed that the bldJ mutant is impaired in expression of genes involved in the uptake of FO, whereas transcription of genes involved in both DFO biosynthesis and FO uptake is increased in bldK mutants. Our study allows proposing altered DFO production and/or FO uptake as a novel phenotypic marker of many S. coelicolor bld mutants, and strengthens the role of siderophores and iron acquisition in morphological development of actinomycetes.

Unsuspected control of siderophore production by N-acetylglucosamine in streptomycetes.

Iron is one of the most abundant elements on earth but is found in poorly soluble forms hardly accessible to microorganisms. To subsist, they have developed iron-chelating molecules called siderophores that capture this element in the environment and the resulting complexes are internalized by specific uptake systems. While biosynthesis of siderophores in many bacteria is regulated by iron availability and oxidative stress, we describe here a new type of regulation of siderophore production. We show that in Streptomyces coelicolor, their production is also controlled by N-acetylglucosamine (GlcNAc) via the direct transcriptional repression of the iron utilization repressor dmdR1 by DasR, the GlcNAc utilization regulator. This regulatory nutrient-metal relationship is conserved among streptomycetes, which indicates that the link between GlcNAc utilization and iron uptake repression, however unsuspected, is the consequence of a successful evolutionary process. We describe here the molecular basis of a novel inhibitory mechanism of siderophore production that is independent of iron availability. We speculate that the regulatory connection between GlcNAc and siderophores might be associated with the competition for iron between streptomycetes and their fungal soil competitors, whose cell walls are built from the GlcNAc-containing polymer chitin. Alternatively, GlcNAc could emanate from streptomycetes' own peptidoglycan that goes through intense remodelling throughout their life cycle, thereby modulating the iron supply according to specific needs at different stages of their developmental programme.