Disruption of the siderophore‐binding desE receptor gene in Streptomyces coelicolor A3(2) results in impaired growth in spite of multiple iron–siderophore transport systems

Abstract

SummaryFerrioxamines‐mediated iron acquisition by Streptomyces coelicolor A3(2) has recently received increased attention. In addition to the biological role of desferrioxamines (dFOs) as hydroxamate siderophores, and the pharmaceutical application of dFO‐B as an iron‐chelator, the ferrioxamines have been shown to mediate microbial interactions. In S. coelicolor the siderophore‐binding receptors DesE (Sco2780) and CdtB (Sco7399) have been postulated to specifically recognize and uptake FO‐E (cyclic) and FO‐B (linear) respectively. Here, disruption of the desE gene in S. coelicolor, and subsequent phenotypic analysis, is used to demonstrate a link between iron metabolism and physiological and morphological development. Streptomyces coelicolor desE mutants, isolated in both wild‐type (M145) and a coelichelin biosynthesis and transport minus background (mutant W3), a second hydroxamate siderophore system only found in S. coelicolor and related species, resulted in impaired growth and lack of sporulation. This phenotype could only be partially rescued by expression in trans of either desE and cdtB genes, which contrasted with the ability of FO‐E, and to a lesser extent of FO‐B, to fully restore growth at µM concentrations, with a concomitant induction of a marked phenotypic response involving precocious synthesis of actinorhodin and sporulation. Moreover, growth restoration of the desE mutant by complementation with desE and cdtB showed that DesE, which is universally conserved in Streptomyces, and CdtB, only present in certain streptomycetes, have partial equivalent functional roles under laboratory conditions, implying overlapping ferrioxamine specificities. The biotechnological and ecological implications of these observations are discussed.

Interspecies modulation of bacterial development through iron competition and siderophore piracy

“…() found that disruption of the deferrioxamine importer desE led to impaired development on solid R2YE medium. Likewise, they found that adding 2,2′‐dipyridyl, an iron‐chelating compound commonly employed to induce iron starvation in bacteria (Outten et al ., ; Tierrafria et al ., ), also delayed the appearance of aerial hyphae. Our findings of the preceding sections, and those of Tierrafria et al .…”

“…Our findings of the preceding sections, and those of Tierrafria et al . (), therefore motivated us to examine the effect of iron availability on the expression of S. coelicolor developmental genes. To this end, we grew S. coelicolor on medium containing between 0 μM and 100 μM added FeCl 3 or on medium containing between 50 μM and 200 μM 2,2′‐dipyridyl.…”

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

“…28,29 Taken together, these results demonstrate that inhibition of development and antibiotic production by physiological signalling can also be circumvented by potentiating siderophore-mediated iron uptake in S. coelicolor. [9][10][11] Transcription of iron-and development-related genes in bldA, bldJ and bldK mutants…”

“…6,9 In line with these findings, Tierrafria and collaborators showed that the disruption of the desferrioxamine-binding receptor encoded by desE resulted in loss of sporulation in S. coelicolor. 10 Recently, co-culture experiments demonstrated that iron competition through siderophore piracy between actinomycetes prevented S. coelicolor from entering its sporulation program. 11 Pathways leading to the onset of sporulation are numerous and diverse among bacteria and Streptomyces are no exception.…”

Editorial – preview

“…The siderophore‐binding receptor DesE is abundant among streptomycetes, while the CdtB counterpart is only found in certain Streptomyces species. Based on the analyses of mutants, Tierrafría and colleagues (2011) conclude that DesE and CdtB have overlapping ferrioxamine specificities. Due to additional studies, and the fact that genes for synthesis of desferrioxamines are abundant among streptomycetes, the authors speculate about an additional regulatory or signalling role of siderophores.…”