| Congresso Brasileiro de Microbiologia 2023 | Resumo: 516-1 | ||||
Resumo:Fungal infections and antifungal resistance are a growing public health problem, with a limited arsenal of antifungal drug classes to tackle. Besides, antifungal therapy presents several disadvantages in terms of therapeutic failures, side effects and toxicities, drug interactions, and prolonged therapies. The development of future therapeutic agents is crucial. Bacterial natural products are the source of most antimicrobial drugs in clinical use, and actinomycetes are well-recognized factories of lead compounds in drug discovery. In this work, we screened 14 actinomycetes lineages maintained by Coleção Brasileira de Microrganismos de Ambiente e Indústria (CBMAI-Unicamp) culture collection, which presented biotechnological potential (e.g., anticancer, antibacterial, antiviral action) in previous research, against fungal pathogens (n=16) in search for antifungal metabolites producing strains. The fungal strains tested are maintained by the Laboratório de Investigação em Fungos (LIF-Unicamp) culture collection and encompass yeasts and molds retrieved from Unicamp Clinical Hospital patients, including Candida spp. (n=3), Cryptococcus spp. (n=2), Aspergillus spp. (n=2) and Tricophyton (n=1) susceptible isolates, two Candida albicans and four Aspergillus fumigatus that carry drug-resistance mutations, and the “super yeast” Candida auris. We employed the antagonism test for this screening by performing the dual culture assay for molds and strike plate assay for yeasts. The MALDI-TOF-based IDBac bioinformatics platform was employed to organize the groups of taxa based on their protein fingerprints (3−15 kDa) and further correlate with the bioactivity results. Six (43%) actinomycetes were able to inhibit the growth of all tested fungal strains. All bioactive strains belong to the genus Streptomyces, four of which were recovered from extreme environments (Antarctica and Peruvian saline lagoon), which increases the chance of novel molecule discovery since these environments select organisms that produce specialized metabolites. Two of the bioactive strains [CBMAI 1855 (Streptomyces albidoflavus) and B-81 (Streptomyces olivaceus)] had their genome previously sequenced and their biosynthetic gene clusters (BGCs) characterized by the antiSMASH genome mining plataform, revealing a high biosynthetic potential. By re-analyzing their BGCs focusing on clusters encoding compounds with antifungal activity, several of them were found in either genome. Metabolite annotation and Minimum Inhibitory Concentration (MIC) tests of the actinomycetes extracts are the important next steps in this study, as well as providing BGCs characterization of the promising antifungal antagonists. The bacterial and fungal strains used in this study are available for researchers upon request under the CBMAI and LIF culture collections, which possess authentic microorganisms that can support a range of biomedical and biotechnological research, as well as diagnostic testing, and can generate meaningful scientific results. In conclusion, six lineages of Actinobacteria investigated here appear to have great potential as a source for the future discovery of a novel antifungal active agent. Palavras-chave: Actinomycetes, Antifungals, Bioprospection, Culture collections, Natural products Agência de fomento:Fundação de Amparo à Pesquisa do Estado de São Paulo | |||||