Mefenoxam and pyraclostrobin: toxicity and in vitro inhibitory activity against Pythium insidiosum

Abstract

Significance and Impact of the Study: Pythiosis is a granulomatous disease caused by the pathogenic aquatic oomycete Pythium insidiosum, described mainly in horses, dogs and humans. Widespread especially in tropical, subtropical and temperate regions, this disease has been widely studied in an attempt to develop an effective therapeutic protocol, since there is no standard treatment for pythiosis. This fact justifies this research, which seeks new alternatives to combat this important disease, and shows promising results, as the phytoantifungals under study inhibited the growth of P. insidiosum.

Potential anti- Pythium insidiosum therapeutics identified through screening of agricultural fungicides

“…Some non-conventional drugs/chemicals, such as natural compounds, bacterial metabolites, nanoparticles, antimicrobial peptides, photosensitizers, potassium iodide, triamcinolone, dimethyl sulfoxide (DMSO), ozone, prednisone, and mefenoxam, have been investigated for their inhibitory properties against P. insidiosum ( 5 , 9 – 14 ). Of these, mefenoxam is an agricultural fungicide used to control plant-pathogenic microorganisms, such as Phytophthora cinnamomi , Pythium myriotylum , and Pythium aphanidermatum , that are phylogenetically related to P. insidiosum ( 15 – 17 ).…”

“…Of these, mefenoxam is an agricultural fungicide used to control plant-pathogenic microorganisms, such as Phytophthora cinnamomi , Pythium myriotylum , and Pythium aphanidermatum , that are phylogenetically related to P. insidiosum ( 15 – 17 ). An in vitro susceptibility test of mefenoxam against various P. insidiosum strains revealed a minimal inhibition concentration (MIC) of up to 10 µg/mL ( 14 , 18 ). Another fungicide, pyraclostrobin, demonstrated an in vitro inhibitory effect against 21 P .…”

“…Another fungicide, pyraclostrobin, demonstrated an in vitro inhibitory effect against 21 P . insidiosum strains with MICs of up to 5 µg/mL ( 14 ). Toxicity evaluation using Caenorhabditis elegans showed that the worm could tolerate mefenoxam and pyraclostrobin ( 14 ).…”

“…insidiosum strains with MICs of up to 5 µg/mL ( 14 ). Toxicity evaluation using Caenorhabditis elegans showed that the worm could tolerate mefenoxam and pyraclostrobin ( 14 ). When mefenoxam was administered in combination with common antifungal drugs (itraconazole and terbinafine) and surgical intervention for up to 18 months, this treatment regimen cured six out of seven dogs with pythiosis ( 19 , 20 ).…”

“…Our focus is on commercially available fungicides that inhibit plant-pathogenic oomycetes, but their properties against the human/animal-pathogenic oomycete P. insidiosum have yet to be evaluated. A literature review identified 17 fungicides (i.e., ametoctradin, fosetyl aluminium, pyraclostrobin, copper octanoate, cymoxanil, mancozeb, dimethomorph, oxathiapiprolin, fluopicolide, cyazofamid, fenamidone, mandipropamid, phosphoric acid, propamocarb hydrochloride, azoxystrobin, mefenoxam, and famoxadone) with growth-inhibitory activity against filamentous oomycetes, including Phytophthora , Pseudoperonospora , Plasmopara , and Pythium species ( 14 , 15 , 21 – 27 ). In this study, we evaluated the anti- P .…”