Nitrogen sources enhance siderophore-mediated competition for iron between potato common scab and late blight causative agents.

How do pathogens affecting the same host interact with each other? We evaluated here the types of microbe-microbe interactions taking place between Streptomyces scabiei and Phytophthora infestans, the causative agents of common scab and late blight diseases in potato crops, respectively. Under most laboratory culture conditions tested, S. scabiei impaired or completely inhibited the growth of P. infestans by producing either soluble and/or volatile compounds. Increasing peptone levels correlated with increased inhibition of P. infestans. Comparative metabolomics showed that production of S. scabiei siderophores (desferrioxamines, pyochelin, scabichelin, and turgichelin) increased with the quantity of peptone, thereby suggesting that they participate in the inhibition of the oomycete growth. Mass spectrometry imaging further uncovered that the zones of secreted siderophores and of P. infestans growth inhibition coincided. Moreover, either the repression of siderophore production or the neutralization of their iron-chelating activity led to a resumption of P. infestans growth. Replacement of peptone by natural nitrogen sources such as ammonium nitrate, sodium nitrate, ammonium sulfate, and urea also triggered siderophore production in S. scabiei. Interestingly, nitrogen source-induced siderophore production also inhibited the growth of Alternaria solani, the causative agent of the potato early blight. Overall, our work further emphasizes the importance of competition for iron between microorganisms that colonize the same niche. As common scab never alters the vegetative propagation of tubers, we propose that S. scabiei, under certain conditions, could play a protective role for its hosts against much more destructive pathogens through exploitative iron competition and volatile compound production.

Lunaemycins, New Cyclic Hexapeptide Antibiotics from the Cave Moonmilk-Dweller Streptomyces lunaelactis MM109T.

Streptomyces lunaelactis strains have been isolated from moonmilk deposits, which are calcium carbonate speleothems used for centuries in traditional medicine for their antimicrobial properties. Genome mining revealed that these strains are a remarkable example of a Streptomyces species with huge heterogeneity regarding their content in biosynthetic gene clusters (BGCs) for specialized metabolite production. BGC 28a is one of the cryptic BGCs that is only carried by a subgroup of S. lunaelactis strains for which in silico analysis predicted the production of nonribosomal peptide antibiotics containing the non-proteogenic amino acid piperazic acid (Piz). Comparative metabolomics of culture extracts of S. lunaelactis strains either holding or not holding BGC 28a combined with MS/MS-guided peptidogenomics and 1H/13C NMR allowed us to identify the cyclic hexapeptide with the amino acid sequence (D-Phe)-(L-HO-Ile)-(D-Piz)-(L-Piz)-(D-Piz)-(L-Piz), called lunaemycin A, as the main compound synthesized by BGC 28a. Molecular networking further identified 18 additional lunaemycins, with 14 of them having their structure elucidated by HRMS/MS. Antimicrobial assays demonstrated a significant bactericidal activity of lunaemycins against Gram-positive bacteria, including multi-drug resistant clinical isolates. Our work demonstrates how an accurate in silico analysis of a cryptic BGC can highly facilitate the identification, the structural elucidation, and the bioactivity of its associated specialized metabolites.