Pythium oligandrum (Oomycota) is known for its strong mycoparasitism against more than 50 fungal and oomycete species. However, the ability of this oomycete to suppress and kill the causal agents of dermatophytoses is yet to be studied. We provide a complex study of the interactions between P. oligandrum and dermatophytes representing all species dominating in the developed countries. We assessed its biocidal potential by performing growth tests, on both solid and liquid cultivation media and by conducting a pilot clinical study. In addition, we studied the molecular background of mycoparasitism using expression profiles of genes responsible for the attack on the side of P. oligandrum and the stress response on the side of Microsporum canis. We showed that dermatophytes are efficiently suppressed or killed by P. oligandrum in the artificial conditions of cultivations media between 48 and 72 h after first contact. Significant intra- and interspecies variability was noted. Of the 69 patients included in the acute regimen study, symptoms were completely eliminated in 79% of the patients suffering from foot odour, hyperhidrosis disappeared in 67% of cases, clinical signs of dermatomycoses could no longer be observed in 83% of patients, and 15% of persons were relieved of symptoms of onychomycosis. Our investigations provide clear evidence that the oomycete is able to recognize and kill dermatophytes using recognition mechanisms that resemble those described in oomycetes attacking fungi infecting plants, albeit with some notable differences.

Bio Agens Research and Development BARD Rýznerova 150 25262 Únětice Czech Republic

Biopreparáty spol s r o Rýznerova 150 25262 Únětice Czech Republic

Laboratory of Fungal Genetics and Metabolism Institute of Microbiology Czech Academy of Sciences Vídeňská 1083 14220 Praha 4 Czech Republic

Laboratory of Medical Mycology Department of Microbiology Pardubice Regional Hospital 56024 Pardubice Czech Republic

Zobrazit více v PubMed

Weitzman I, Summerbell RC. The dermatophytes. Clin Microbiol Rev. 1995;8:240–259. PubMed PMC

Achterman RR, White TC. A foot in the door for dermatophyte research. PLoS Pathog. 2012;8:e1002564. doi: 10.1371/journal.ppat.1002564. PubMed DOI PMC

Havlickova B, Czaika VA, Friedrich M. Epidemiological trends in skin mycoses worldwide. Mycoses. 2008;51:2–15. doi: 10.1111/j.1439-0507.2008.01606.x. PubMed DOI

Drake LA, Dinehart SM, Farmer ER, Goltz RW, Graham GF, Hordinsky MK, et al. Guidelines of care for superficial mycotic infections of the skin: tinea corporis, tinea cruris, tinea faciei, tinea manuum, and tinea pedis. J Am Acad Dermatol. 1996;34:282–286. doi: 10.1016/S0190-9622(96)80135-6. PubMed DOI

Achterman RR, White TC. Dermatophyte virulence factors: identifying and analyzing genes that may contribute to chronic or acute skin infections. Int J Microbiol. 2012;2012:358305. doi: 10.1155/2012/358305. PubMed DOI PMC

Martinez DA, Oliver BG, Gräser Y, Goldberg JM, Li W, Martinez-Rossi NM, et al. Comparative genome analysis of Trichophyton rubrum and related dermatophytes reveals candidate genes involved in infection. MBio. 2012;3:e00259-12. doi: 10.1128/mBio.00259-12. PubMed DOI PMC

Chinnapun D. Virulence factors involved in pathogenicity of dermatophytes. Walailak J Sci Technol. 2015;12:573–580.

Asz-Sigall D, Tosti A, Arenas R. Tinea unguium: diagnosis and treatment in practice. Mycopathologia. 2017;182:95–100. doi: 10.1007/s11046-016-0078-4. PubMed DOI

Kumar P, Latka C, Taneja B. Current antifungal therapy and drug resistance mechanisms in dermatophytes. In: Arora G, Sajid A, Kalia V, editors. Drug resistance in bacteria, fungi, malaria, and cancer. Springer: Cham; 2017. pp. 371–385.

Benhamou N, le Floch G, Vallance J, Gerbore J, Grizard D, Rey P. Pythium oligandrum: an example of opportunistic success. Microbiology. 2012;158:2679–2694. doi: 10.1099/mic.0.061457-0. PubMed DOI

Brožová J. Exploitation of the mycoparasitic fungus Pythium oligandrum in plant protection. Plant Prot Sci. 2002;38:29–35.

Lévesque CA, Brouwer H, Cano L, Hamilton JP, Holt C, Huitema E, et al. Genome sequence of the necrotrophic plant pathogen Pythium ultimum reveals original pathogenicity mechanisms and effector repertoire. Genome Biol. 2010;11:R73. doi: 10.1186/gb-2010-11-7-r73. PubMed DOI PMC

Horner NR, Grenville-Briggs LJ, Van West P. The oomycete Pythium oligandrum expresses putative effectors during mycoparasitism of Phytophthora infestans and is amenable to transformation. Fungal Biol. 2012;116:24–41. doi: 10.1016/j.funbio.2011.09.004. PubMed DOI

Jiang RH, Tyler BM. Mechanisms and evolution of virulence in oomycetes. Annu Rev Phytopathol. 2012;50:295–318. doi: 10.1146/annurev-phyto-081211-172912. PubMed DOI

Picard K, Tirilly Y, Benhamou N. Cytological effects of cellulases in the parasitism of Phytophthora parasitica by Pythium oligandrum. Appl Environ Microbiol. 2000;66:4305–4314. doi: 10.1128/AEM.66.10.4305-4314.2000. PubMed DOI PMC

Gerbore J, Benhamou N, Vallance J, Le Floch G, Grizard D, Regnault-Roger C, et al. Biological control of plant pathogens: advantages and limitations seen through the case study of Pythium oligandrum. Environ Sci Pollut Res. 2014;21:4847–4860. doi: 10.1007/s11356-013-1807-6. PubMed DOI

Deacon J. Studies on Pythium oligandrum, an aggressive parasite of other fungi. Trans Br Mycol Soc. 1976;66:383–391. doi: 10.1016/S0007-1536(76)80206-9. DOI

Veselý D. Studies of the mycoparasitism in rhizosphere of emerging sugar-beet. Zentralblatt für Bakteriologie, Parasitenkunde, Infektionskrankheiten und Hygiene Zweite Naturwissenschaftliche Abteilung: Mikrobiologie der Landwirtschaft, der Technologie und des Umweltschutzes. 1978;133:195–200. doi: 10.1016/S0323-6056(78)80001-9. PubMed DOI

Mencl K. Is it possible to influence dermatomycoses by ecological means? Cesk Dermatol. 2002;77:71–75.

Načeradská M, Mencl K. Biopreparation with Pythium oligandrum at the therapy of dermatophytosis in cats-case report. Veterinarstvi. 2010;60:559–563.

Seebacher C, Bouchara JP, Mignon B. Updates on the epidemiology of dermatophyte infections. Mycopathologia. 2008;166:335–352. doi: 10.1007/s11046-008-9100-9. PubMed DOI

Hubka V, Větrovský T, Dobiášová S, Skořepová M, Lysková P, Mencl K, et al. Molecular epidemiology of dermatophytoses in the Czech republic—two-year-study results. Cesko Slov Dermatol. 2015;89:167–174.

Martin FM. Inventor Biocontrol of fungal soilborne pathogens by Pythium oligandrum patent US Patent 5,961,971. 1999.

Hubka V, Dobiasova S, Dobias R, Kolarik M. Microsporum aenigmaticum sp. nov. from M. gypseum complex, isolated as a cause of tinea corporis. Med Mycol. 2014;52:387–396. doi: 10.1093/mmy/myt033. PubMed DOI

Berendzen K, Searle I, Ravenscroft D, Koncz C, Batschauer A, Coupland G, et al. A rapid and versatile combined DNA/RNA extraction protocol and its application to the analysis of a novel DNA marker set polymorphic between Arabidopsis thaliana ecotypes Col-0 and Landsberg erecta. Plant Methods. 2005;1:4. doi: 10.1186/1746-4811-1-4. PubMed DOI PMC

Saunte D, Simmel F, Frimodt-Moller N, Stolle L, Svejgaard E, Haedersdal M, et al. In vivo efficacy and pharmacokinetics of voriconazole in an animal model of dermatophytosis. Antimicrob Agents Chemother. 2007;51:3317–3321. doi: 10.1128/AAC.01185-06. PubMed DOI PMC

Klimeš R, Suchánek M, Maštalková L, Gopfert E, Nedbalcová K, Blahutová A et al. Comparison of the efficacy of treatment of dermatophytosis in guinea pigs by chemical vs. biological antifungals: ecological peronosporomycete Pythium oligandrum is as efficient as the chemical antifungal enilconazole. Vet Dermatol. 2018. (in press).

Zhu Y, Zhou P, Hu J, Zhang R, Ren L, Li M, Ning F, Chen W, Yu L. Characterization of Pythium transcriptome and gene expression analysis at different stages of fermentation. PLoS ONE. 2013;8:e65552. doi: 10.1371/journal.pone.0065552. PubMed DOI PMC

Kozera B, Raoacz M. Reference genes in real-time PCR. J Appl Genet. 2013;54:391–406. doi: 10.1007/s13353-013-0173-x. PubMed DOI PMC

Lutchmeah R, Cooke R. Aspects of antagonism by the mycoparasite Pythium oligandrum. Trans Br Mycol Soc. 1984;83:696–700. doi: 10.1016/S0007-1536(84)80191-6. DOI

Whipps JM. Microbial interactions and biocontrol in the rhizosphere. J Exp Bot. 2001;52:487–511. doi: 10.1093/jxb/52.suppl_1.487. PubMed DOI

Barros MES, Santos DA, Hamdan JS. In vitro methods for antifungal susceptibility testing of Trichophyton spp. Mycol Res. 2006;110:1355–1360. doi: 10.1016/j.mycres.2006.08.006. PubMed DOI

Campion C, Massiot P, Rouxel F. Aggressiveness and production of cell-wall degrading enzymes by Pythium violae, Pythium sulcatum and Pythium ultimum, responsible for cavity spot on carrots. Eur J Plant Pathol. 1997;103:725–735. doi: 10.1023/A:1008657319518. DOI

Natarajan C, Gupta V, Kumar K, Prasanna R. Molecular characterization of a fungicidal endoglucanase from the cyanobacterium Calothrix elenkinii. Biochem Genet. 2013;51:766–779. doi: 10.1007/s10528-013-9605-x. PubMed DOI

Judelson HS. The genetics and biology of Phytophthora infestans: modern approaches to a historical challenge. Fungal Genet Biol. 1997;22:65–76. doi: 10.1006/fgbi.1997.1006. PubMed DOI

Grenville-Briggs LJ, Horner NR, Phillips AJ, Beakes GW, Van West P. A family of small tyrosine rich proteins is essential for oogonial and oospore cell wall development of the mycoparasitic oomycete Pythium oligandrum. Fungal Biol. 2013;117:163–172. doi: 10.1016/j.funbio.2013.01.001. PubMed DOI

Novel approach of dermatophytosis eradication in shelters: effect of Pythium oligandrum on Microsporum canis in FIV or FeLV positive cats

An Outbreak of Trichophyton quinckeanum Zoonotic Infections in the Czech Republic Transmitted from Cats and Dogs

Comparative eco-physiology revealed extensive enzymatic curtailment, lipases production and strong conidial resilience of the bat pathogenic fungus Pseudogymnoascus destructans

Novel Insights into the Effect of Pythium Strains on Rapeseed Metabolism