Antifungal and Immunomodulatory Activities of Brazilian Savannah Solanum lypocarpum Tree-Associated Streptomyces Isolates

<b>Background/Objectives:</b> Actinobacteria are one of the largest bacterial phyla. These microbes produce bioactive compounds, such as antifungals, antibiotics, immunological modulators, and anti-tumor agents. Studies on actinobacteria isolated from the Brazilian Savannah biome (Cerrado) are scarce and mostly address metagenomics or the search for hydrolytic enzyme-producing microbes. <i>Solanum lycocarpum</i> (lobeira) is a tree widely employed in regional gastronomy and pharmacopeia in Central Brazil. <b>Methods:</b> In this work, 60 actinobacteria isolates were purified from the rhizosphere of <i>S. lycocarpum</i>. Eight <i>Streptomyces</i> spp. isolates were selected for in vitro antifungal activity against <i>Cryptococcus neoformans</i> H99, the <i>C. neoformans</i> 89-610 fluconazole-tolerant strain, <i>C. gattii</i> NIH198, <i>Candida albicans</i>, <i>C. glabrata,</i> and <i>C. parapsilosis</i>. The ability of the aqueous extracts of the isolates to induce the in vitro secretion of tumor necrosis factor (TNF-α), nitric oxide (NO), interleukin-6 (IL-6), and IL-10 by murine macrophages was also evaluated. <b>Results:</b> All extracts showed antifungal activity against at least two yeast species. <i>Streptomyces</i> spp. LAP11, LDB2, and LDB17 inhibited <i>C. neoformans</i> growth by 40-93%. Most extracts (except LAP2) also inhibited <i>C. gattii</i>. None inhibited <i>C. albicans</i>, but all inhibited <i>C. glabrata</i> (40-90%). <i>Streptomyces</i> sp. LAP8 extract increased nitric oxide production by approximately 347-fold in murine macrophages, while LDB11 extract suppressed LPS-induced TNF-α production by 70% and simultaneously increased IL-10 secretion, suggesting immunosuppressive potential. <b>Conclusions:</b> The results revealed that Cerrado actinobacteria-derived aqueous extracts are potential sources of antifungal and immunomodulatory biocompounds.