Emerging and re-emerging microbial pathogens, together with their rapid evolution and adaptation against antibiotics, highlight the importance not only of screening for new antimicrobial agents, but also for deepening knowledge about existing antibiotics. Primycin is a large 36-membered non-polyene macrolide lactone exclusively produced by Saccharomonospora azurea. This study provides information about strain dependent primycin production ability in conjunction with the structural, functional and comparative genomic examinations. Comparison of high- and low-primycin producer strains, transcriptomic analysis identified a total of 686 differentially expressed genes (DEGs), classified into diverse Cluster of Orthologous Groups. Among them, genes related to fatty acid synthesis, self-resistance, regulation of secondary metabolism and agmatinase encoding gene responsible for catalyze conversion between guanidino/amino forms of primycin were discussed. Based on in silico data mining methods, we were able to identify DEGs whose altered expression provide a good starting point for the optimization of fermentation processes, in order to perform targeted strain improvement and rational drug design.

Primycin is a 36-membered marginolactone antibiotic that is biosynthesized through the modular type I polyketide synthase pathway produced by Saccharomonospora azurea, a Gram-positive, soil-dwelling filamentous bacteria. In industrial-scale batch fermentation the primycin-producing strain is cultivated in a complex fermentation media empirically optimized for antibiotic production. To determine the role of various fatty acids on primycin production, the effect of stearic acid (C18:0), palmitic acid (C16:0), lauric acid (C12:0), capric acid (C10:0), enanthic acid (C7:0), caproic acid (C6:0), and butyric acid (C4:0) in growth medium was studied. Our results clearly show that palmitic acid was a better alternative of the originally applied stearic acid in all tested concentrations, while 4.5 g/L proved to be the most effective.

The SARS-CoV-2 infections are considered as respiratory system diseases, mostly. In COVID-19, it might also be the infection of gastrointestinal (GI) tract too, especially at patients in severe clinical condition. SARS-CoV-2 can destroy the intestinal barrier, capable to spread into internal organs via blood and/or lymphatic circulation, and to cause serious damage there. Infected GI tract of COVID-19 patients is ideal environment for the coronavirus infection, replication and as virus reservoir might be the major source of pandemic reinfections, too. The process of virus budding is dependent on the host cell lipid rafts containing membrane-sterols, mainly cholesterol. The viral envelope may be challenged by polyene antibiotics, such as nystatin, which has strong affinity to sterols. Nystatin may block the establishment of the virus-host cell connection, too. In this study, the nystatin was investigated, as antiviral agent to SARS-CoV-2. We demonstrated by tests in Vero E6 cell based cytopathic assay, nystatin blocked the replication of SARS-CoV-2 in concentration 62.5 μg/ml (IC50) at Wuhan and British mutant strains. No efficient SARS-CoV-2 antiviral agent is known so far to alleviate pandemic, to disinfect GI tract, where vaccines might have limited effect, only. Nystatin might be the first one with emergency use authorization, either, as a safe and efficient non-systemic antiviral drug, with well-established use, since decades.