Abstract:
:Invasive fungal diseases are generally difficult to treat and often fatal. The therapeutic agents available to treat fungi are limited, and there is a critical need for new agents to combat these deadly infections. Antifungal compound development has been hindered by the challenge of creating agents that are highly active against fungal pathogens but not toxic to the host. Host defense peptides (HDPs) are produced by eukaryotes as a component of the innate immune response to pathogens and have served as inspiration for the development of many new antibacterial compounds. HDP mimics, however, have largely failed to exhibit potent and selective antifungal activity. Here, we present an HDP-like nylon-3 copolymer that is effective against diverse fungi while displaying only mild to moderate toxicity toward mammalian cells. This polymer is active on its own and in synergy with existing antifungal drugs against multiple species of Candida and Cryptococcus, reaching levels of efficacy comparable to those of the clinical agents amphotericin B and fluconazole in some cases. In addition, the polymer acts synergistically with azoles against different species of Aspergillus, including some azole-resistant strains. These findings indicate that nylon-3 polymers are a promising lead for development of new antifungal therapeutic strategies.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Rank LA,Walsh NM,Liu R,Lim FY,Bok JW,Huang M,Keller NP,Gellman SH,Hull CMdoi
10.1128/AAC.00204-17subject
Has Abstractpub_date
2017-09-22 00:00:00issue
10eissn
0066-4804issn
1098-6596pii
AAC.00204-17journal_volume
61pub_type
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