Streptomycesdevelopment is involved in the efficient containment of viral infections

Abstract

The formation of plaques represents the hallmark of phage infection visualizing the clearance of the bacterial lawn in structured environments. In this study, we have addressed the impact of cellular development on phage infection in Streptomyces undergoing a complex developmental life cycle. Analysis of plaque dynamics revealed, after a period of plaque size enlargement, a significant regrowth of transiently phage-resistant Streptomyces mycelium into the lysis zone. Analysis of Streptomyces venezuelae mutant strains defective at different stages of cellular development indicated that this regrowth was dependent on the onset of the formation of aerial hyphae and spores at the infection interface. Mutants restricted to vegetative growth (ΔbldN) featured no significant constriction of plaque area. Fluorescence microscopy further confirmed the emergence of a distinct zone of cells/spores with reduced cell permeability towards propidium iodide staining at the plaque periphery. Mature mycelium was further shown to be significantly less susceptible to phage infection, which is less pronounced in strains defective in cellular development. Transcriptome analysis revealed the repression of cellular development at the early stages of phage infection probably facilitating efficient phage propagation. We further observed an induction of the chloramphenicol biosynthetic gene cluster highlighting phage infection as a trigger of cryptic metabolism in Streptomyces. Altogether, our study emphasizes cellular development and the emergence of transient phage resistance as an important layer of Streptomyces antiviral immunity.

Complete genomes and comparative analyses of Streptomyces phages that influence secondary metabolism and sporulation

“…As secondary metabolite production is tightly linked to sporulation in Streptomyces, these effects may also be linked to the acceleration of sporulation observed in S. coelicolor, WAC178, and WAC288 in response to phage infection. Our results, in combination with recent work showing induction of chloramphenicol and accelerated sporulation in S. venezuelae in response to phage infection 17 , suggest a variety of developmental changes are triggered in Streptomyces in response to phage infection. Understanding the complex interplay between Streptomyces and the phages that infect them has the potential to deepen our understanding of Streptomyces bacteria, uncover novel secondary metabolites, and improve our understanding of the role of secondary metabolites in the phagehost evolutionary arms race.…”

“…formed plaques poorly at 15 hours, suggesting that this phage was more sensitive to some cellular factor that is differentially expressed during the Streptomyces life cycle. None of the phages were able to e ciently replicate in mature mycelia, which is consistent with previous work showing that Streptomyces phages replicate best in exponentially growing cells 17,45,46 .…”

“…6b,c). As Streptomyces phages replicate only in exponentially growing cells 17,45,46 , this hastening of sporulation may be an adaptive response to allow cells within the colony to become phage resistant and limit the phage epidemic.…”

Characterization of a novel temperate phage facilitatingin vitrodispersal of multicellular bacteria

“…Reciprocally, some bioactive compounds produced by Streptomyces can act as anti-phage defenses (12)(13)(14). Furthermore, some Streptomyces phages encode 3 homologs of sporulation and antibiotic production regulators (15), and can impact the developmental cycle of Streptomyces (11). Reciprocally, susceptibility to phage infection varies along this cycle (11,16).…”

Genomic characterization of the antiviral arsenal of Actinobacteria

“…Yet, the unique characteristics of certain Actinobacteria might influence their anti-phage arsenal. For instance, the susceptibility to phage infection of actinobacterial species can vary depending on diverse development stages and cell forms [16]. It was also recently discovered that among the bioactive compounds produced by Actinobacteria, some display anti-phage activity [17,18], suggesting links between their biosynthetic ability and the defence systems they encode.…”