| Summary: | Systemic mycoses have become a major cause of morbidity and mortality, particularly among immunocompromised hosts and long-term hospitalized patients. Conventional antifungal agents are limited because of not only their costs and toxicity but also the rise of resistant strains. Lipopeptides from <i>Paenibacillus</i> species exhibit antimicrobial activity against a wide range of human and plant bacterial pathogens. However, the antifungal potential of these compounds against important human pathogens has not yet been fully evaluated, except for <i>Candida albicans</i>. <i>Paenibacillus elgii</i> produces a family of lipopeptides named pelgipeptins, which are synthesized by a non-ribosomal pathway, such as polymyxin. The present study aimed to evaluate the activity of pelgipeptins produced by <i>P. elgii</i> AC13 against <i>Cryptococcus neoformans</i>, <i>Paracoccidioides brasiliensis</i>, and <i>Candida</i> spp. Pelgipeptins were purified from <i>P. elgii</i> AC13 cultures and characterized by high-performance liquid chromatography (HPLC) and mass spectrometry (MALDI-TOF MS). The <i>in vitro</i> antifugal activity of pelgipeptins was evaluated against <i>C. neoformans</i> H99, <i>P. brasiliensis</i> PB18, <i>C. albicans</i> SC 5314, <i>Candida glabrata</i> ATCC 90030, and <i>C. albicans</i> biofilms. Furthermore, the minimal inhibitory concentration (MIC) was determined according to the CLSI microdilution method. Fluconazole and amphotericin B were also used as a positive control. Pelgipeptins A to D inhibited the formation and development of <i>C. albicans</i> biofilms and presented activity against all tested microorganisms. The minimum inhibitory concentration values ranged from 4 to 64 µg/mL, which are in the same range as fluconazole MICs. These results highlight the potential of pelgipeptins not only as antimicrobials against pathogenic fungi that cause systemic mycoses but also as coating agents to prevent biofilm formation on medical devices.
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