Background: Scedosporium/Lomentospora species are human pathogens that are resistant to almost all antifungals currently available in clinical practice. Methods: The effects of 16 1,10-phenanthroline (phen)/1,10-phenanthroline-5,6-dione/dicarboxylate chelates containing Cu(II), Mn(II) and Ag(I) against Scedosporium apiospermum, Scedosporium minutisporum, Scedosporium aurantiacum and Lomentospora prolificans were evaluated. Results: To different degrees, all of the test chelates inhibited the viability of planktonic conidial cells, displaying MICs ranging from 0.029 to 72.08 μM. Generally, Mn(II)-containing chelates were the least toxic to lung epithelial cells, particularly [Mn2(oda)(phen)4(H2O)2][Mn2(oda)(phen)4(oda)2].4H2O (MICs: 1.62-3.25 μM: selectivity indexes >64). Moreover, this manganese-based chelate reduced the biofilm biomass formation and diminished the mature biofilm viability. Conclusion: [Mn2(oda)(phen)4(H2O)2][Mn2(oda)(phen)4(oda)2].4H2O opens a new chemotherapeutic avenue for the deactivation of these emergent, multidrug-resistant filamentous fungi.
Keywords: 1,10-phenanthroline; Scedosporium/Lomentospora; antifungal resistance; biofilm; chemotherapy; coordination compounds.
Metals have been used to treat microbial infections for centuries. In this context, the effects of 16 metal-based compounds against the human pathogens Scedosporium apiospermum, Scedosporium minutisporum, Scedosporium aurantiacum and Lomentospora prolificans were tested. All the 16 metal-based compounds were able to interfere with the viability of these fungal pathogens to different degrees. Among the 16 compounds, a manganese-containing compound presented the best activity against the fungal species and it presented the least toxicity to a human lung cell line. In addition, this manganese-containing compound reduced the ability of fungal cells to come together and form a type of community called biofilm. In conclusion, the manganese-containing compound presents a promising option against the multidrug-resistant filamentous fungi species belonging to the Scedosporium/Lomentospora genera.