Clioquinol and 8-hydroxyquinoline-5-sulfonamide derivatives damage the cell wall of Pythium insidiosum

J Appl Microbiol. 2022 Dec 14:lxac038. doi: 10.1093/jambio/lxac038. Online ahead of print.

Abstract

Aims: To evaluate the antimicrobial activity and to determine the pharmacodynamic characteristics of three 8-hydroxyquinoline derivatives (8-HQs) against Pythium insidiosum, the causative agent of pythiosis.

Methods and results: Antimicrobial activity was tested by broth microdilution and MTT assays. The antimicrobial mode of action was investigated using sorbitol protection assay, ergosterol binding assay, and scanning electron microscopy. Clioquinol, PH151, and PH153 were active against all isolates, with MIC values ranging from 0.25 to 2 µg ml-1. They also showed a time- and dose-dependent antimicrobial effect, damaging the P. insidiosum cell wall.

Conclusions: Together, these results reinforce the potential of 8-HQs for developing new drugs to treat pythiosis.

Keywords: Pythium insidiosum; 8-hydroxyquinoline derivatives; antimicrobial activity; clioquinol; mechanism of action.

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