New antifungal 4-chloro-3-nitrophenyldifluoroiodomethyl sulfone reduces the Candida albicans pathogenicity in the Galleria mellonella model organism

Monika Staniszewska , Małgorzata Gizińska , Michalina Kazek , Roberto de Jesús González-Hernández , Zbigniew Ochal , Hector M. Mora-Montes

Abstract

Candida albicans represents an interesting microorganism to study complex host-pathogen interactions and for the development of effective antifungals. Our goal was to assess the efficacy of 4-chloro-3-nitrophenyldifluoroiodomethyl sulfone (named Sulfone) against the C. albicans infections in the Galleria mellonella host model. We assessed invasiveness of CAI4 parental strain and mutants: kex2Δ/KEX2 and kex2Δ/kex2Δ in G. mellonella treated with Sulfone. We determined that KEX2 expression was altered following Sulfone treatment in G. mellonella-C. albicans infection model. Infection with kex2Δ/kex2Δ induced decreased inflammation and minimal fault in fitness of larvae vs CAI4. Fifty percent of larvae died within 4–5 days (P value< 0.0001) when infected with CAI4 and kex2Δ/KEX2 at 109 CFU/mL; survival reached 100% in those injected with kex2Δ/kex2Δ. Larvae treated with Sulfone at 0.01 mg/kg 30 min before infection with all C. albicans tested survived infection at 90–100% vs C. albicans infected-PBS-treated larvae. Hypersensitive to Sulfone, kex2Δ/kex2Δ reduced virulence in survival. KEX2 was down-regulated when larvae were treated with Sulfone: 30 min before and 2 h post-SC5314-wild-type infection respectively. kex2Δ/kex2Δ was able to infect larvae, but failed to kill host when treated with Sulfone. Sulfone can be used to prevent or treat candidiasis. G. mellonella facilitates studding of host-pathogen interactions, i.e., testing host vs panel of C. albicans mutants when antifungal is dosed.