Iron competition triggers antibiotic biosynthesis in Streptomyces coelicolor during coculture with Myxococcus xanthus

Abstract

Microbial coculture to mimic the ecological habitat has been suggested as an approach to elucidate the effect of microbial interaction on secondary metabolite biosynthesis of Streptomyces. However, because of chemical complexity during coculture, underlying mechanisms are largely unknown. Here, we found that iron competition triggered antibiotic biosynthesis in Streptomyces coelicolor during coculture with Myxococcus xanthus. During coculture, M. xanthus enhanced the production of a siderophore, myxochelin, leading M. xanthus to dominate iron scavenging and S. coelicolor to experience iron-restricted conditions. This chemical competition, but not physical contact, activated the actinorhodin biosynthetic gene cluster and the branched-chain amino acid degradation pathway which imply the potential to produce precursors, along with activation of a novel actinorhodin export system. Furthermore, we found that iron restriction increased the expression of 21 secondary metabolite biosynthetic gene clusters (smBGCs) in other Streptomyces species. These findings suggested that the availability for key ions stimulates specific smBGCs, which had the potential to enhance secondary metabolite biosynthesis in Streptomyces.

The antibiotic crisis: How bacterial predators can help

“…Moreover, M. xanthus supernatants and secreted outer membrane vesicles (OMVs, see below) also induced changes in the expression of large numbers of prey genes. Another transcriptomic analysis confirmed the actinorhodin overproduction observed in Streptomyces by Pérez et al [168] , and confirmed that it is iron competition during this interaction which leads to the activation of actinorhodin BGC plus 21 other SM BGCs [172] ( Fig. 3 A).…”

Alteration of protein homeostasis mediates the interaction of Pseudomonas aeruginosa with Staphylococcus aureus

“…In addition to QS‐related proteins, proteins (e.g., PchA, PchC, and PchG) associated with the biosynthesis of siderophores (Youard et al , 2011) are also the potential substrates of P. aeruginosa ClpXP (see supplementary information Data set ). It is tempting to speculate that ClpXP deficiency might increase the ability of P. aeruginosa to acquire iron and thus contribute to the killing of S. aureus by P. aeruginosa , given that the siderophore‐mediated iron competition is important for interspecies interactions (Traxler et al , 2012; Leinweber et al , 2018; Lee et al , 2020; Kramer et al , 2020). However, this hypothesis remains to be verified experimentally.…”

Genome-scale determination of 5´ and 3´ boundaries of RNA transcripts in Streptomyces genomes

“…Despite their potential for the production of diverse secondary metabolites, most of the smBGCs have not been characterized in terms of their products and corresponding molecular functions, mainly due to the silent nature of the smBGCs under the laboratory culture conditions 8 . Since most secondary metabolites are not essential for growth and produced to respond to environmental stimuli, such as osmotic pressure or nutrient limitations or inter-species competition, the smBGCs are expected to be under tight and complex regulation [9][10][11] . To utilize the genomic potential of Streptomyces, an understanding of the genetic regulatory mechanisms for activating smBGCs is crucial.…”