On the nosological affiliation of mycosis caused by the fungus Trichophyton indotineae

The article provides a general description of dermatomycetes (dermatophytes) as a non-systematic group of parasitic fungi, data on the factors of their aggression and virulence are summarized, and the main features of the clinical picture of skin mycosis caused by T. indotineae (indotine‑ mycosis), a new fungus, which many molecular geneticists consider to be an independent species, are listed. Doubts are expressed about the self-activity of this species within the genus Trichophyton, since to date there has been practically no serious microbiological description of its macro‑ and micromorphology. The clinical picture of skin mycosis caused by T. indotineae fully fits into the concept of «trichophytia», as this mycosis should be further classified.

1. Dubljanin E., Zunic J., Vujcic I., Colovic Calovski I., Sipetic Grujicic S., Mijatovic S., Dzamic A. Host Pathogen Interaction and Resistance Mechanisms in Dermatophytes. Pathogens. 2024 Aug 4; 13 (8): 657. DOI: 10.3390/pathogens13080657

2. Martinez Rossi N.M., Persinoti G.F., Peres N.T., Rossi A. Role of pH in the pathogenesis of dermatophytoses. Mycoses. 2012; 55: 381–387. DOI: 10.1111/j.1439–0507.2011.02162.x.

3. Martinez Rossi N.M., Peres N.T.A., Bitencourt T.A., Martins M.P., Rossi A. State of the Art Dermatophyte Infections: Epidemiology Aspects, Pathophysiology, and Resistance Mechanisms. J Fungi (Basel). 2021; 7 (8): 629. DOI: 10.3390/jof7080629.

4. Kalinin A.E., Kajava A.V., Steinert P.M. Epithelial barrier function: Assembly and structural features of the cornified cell envelope. BioEssays. 2000; 24: 789–800. DOI: 10.1002/bies.10144.

5. Ciesielska A., Kawa A., Kanarek K., Soboń A., Szewczyk R. Metabolomic analysis of Trichophyton rubrum and Microsporum canis during keratin degradation. Sci. Rep. 2021; 11: 3959. DOI: 10.1038/s41598–021–83632-z.

6. Monod M. Secreted Proteases from Dermatophytes. Mycopathologia. 2008; 166: 285–294. DOI: 10.1007/s11046-008-9105-4.

7. Chua W., Poh S.E., Li H. Secretory Proteases of the Human Skin Microbiome. Infect. Immun. 2022; 90: e0039721. DOI: 10.1128/IAI.00397–21.

8. AL Khikani F.H. Dermatophytosis a worldwide contiguous fungal infection: Growing challenge and few solutions. Biomed. Biotechnol. Res. J. 2020; 4: 117–122. DOI: 10.4103/bbrj.bbrj_1_20.

9. Long S., Carveth H., Chang Y.M., O’Neill D., Bond R. Isolation of dermatophytes from dogs and cats in the South of England between 1991 and 2017. Veterinary Record. 2020; 187: e87. DOI: 10.1136/vr.105957

10. Kaplan E., Gonca S., Kandemir H., Döğen A., Hilmioğlu Polat S., Ilkit M., et al. Genes Encoding Proteolytic Enzymes Fungalysin and Subtilisin in Dermatophytes of Human and Animal Origin: A Comparative Study. Mycopathologia. 2020; 185: 137–144. DOI: 10.1007/s11046-019-00367-2.

11. Khedmati E., Hazaveh S.J.H., Bayat M., Amini K. Identification of subtilisin virulence genes (SUB1–7) in Epidermophyton floccosum isolated from patients with dermatophytosis in Iran. Gene Rep. 2020; 20: 100748. DOI: 10.1016/j.genrep.2020.100748.

12. Naeimipour F., Hashemi S.J., Rezaie S., Bayat M. Subtilisin Gene Activity in Dermatophytes: A study on the Presence of the Subtilisin Gene in Trichophyton verrucosum and Microsporum gypseum in Clinical and Nonclinical Samples in Tehran, Iran. Arch. Razi Inst. 2021; 76: 253–259. DOI: 10.22092/ari.2019.126417.1343.

13. Mercer D.K., Stewart C.S. Keratin hydrolysis by dermatophytes. Med. Mycol. 2019; 57: 13–22. DOI: 10.1093/mmy/myx160.

14. Kalinin A.E., Kajava A.V., Steinert P.M. Epithelial barrier function: Assembly and structural features of the cornified cell envelope. BioEssays. 2000; 24: 789–800. DOI: 10.1002/bies.10144.

15. Martins Santana L., Petrucelli M.F., Sanches P.R., Martinez Rossi N.M., Rossi A. Peptidase Regulation in Trichophyton rubrum Is Mediated by the Synergism Between Alternative Splicing and StuA Dependent Transcriptional Mechanisms. Front. Microbiol. 2022; 13: 930398. DOI: 10.3389/fmicb.2022.930398.

16. Neves da Rocha J., Santos Saboya M.J., Lopes M.E.R., Rossi A., Martinez Rossi N.M. Insights and Perspectives on the Role of Proteostasis and Heat Shock Proteins in Fungal Infections. Microorganisms. 2023; 11: 1878. DOI: 10.3390/microorganisms11081878.

17. Sardana K., Gupta A., Mathachan S.R. Immunopathogenesis of Dermatophytoses and Factors Leading to Recalcitrant Infections. Indian Dermatol. Online J. 2021; 12: 389–399. DOI: 10.4103/idoj.IDOJ_503_20.

18. Burstein V.L., Beccacece I., Guasconi L., Mena C.J., Cervi L., Chiapello L.S. Skin Immunity to Dermatophytes: From Experimental Infection Models to Human Disease. Front. Immunol. 2020; 11: 605644. DOI: 10.3389/fimmu.2020.605644

19. García Romero M.T., Arenas R. New insights into genes, immunity, and the occurrence of dermatophytosis. J. Investig. Dermatol. 2015; 135: 655–657. DOI: 10.1038/jid.2014.498.

20. Gnat S., Nowakiewitcz A., Lagowski D., Zieba P. Host and pathogen dependent susceptibility and predisposition to dermatophytosis. J. Med. Microbiol. 2019; 68: 823–836. DOI: 10.1099/jmm.0.000982.

21. Celestrino G.A., Verrinder Veasey J., Benard G., Sousa M.G.T. Host immune responses in dermatophytes infection. Mycoses. 2021; 64: 477–483. DOI: 10.1111/myc.13246.

22. Lanternier F., Pathan S., Vincent Q.B., Liu L., Cypowyj S., Prando C., Migaud M., Taibi L., Ammar Khodja A., Stambouli O.B., et al. Deep dermatophytosis and inherited CARD9 deficiency. N. Engl. J. Med. 2013; 369: 1704–1714. DOI: 10.1056/NEJMoa1208487

23. Caplan A.S., Todd G.C., Zhu Y., Sikora M., Akoh C.C., Jakus J., Lipner S.R., et al. Clinical Course, Antifungal Susceptibility, and Genomic Sequencing of Trichophyton indotineae. JAMA Dermatol. 2024; 160 (7): 701–709. DOI: 10.1001/jamadermatol.2024.1126.

24. Гущин А. Е., Романова И. В., Ильин Л. А., Потекаев Н. Н. Первое описание случаев поверхностных микозов, вызванных устойчивым к аллиламинам (тербинафину) «индийским» видом дерматомицетов – Trichophyton indotineae, в Российской дерматовенерологической практике // Клиническая дерматология и венерология. 2024; 23 (5): 581–590. DOI: 10.17116/klinderma202423051581

25. Gushchin A.E., Romanova I.V., Ilyin L.A., Potekaev N.N. The first description of cases of superficial mycoses caused by the allylamine (terbinafine) resistant “Indian” species of dermatomycetes – Trichophyton indotineae, in Russian dermatovenereological practice // Clinical dermatology and venereology. 2024; 23 (5): 581 – 590. (In Russ.). DOI: 10.17116/klinderma202423051581

26. Пчелин И.М., Сергеев А.Ю. Лекарственная устойчивость дерматофитов: грозит ли нам появление индийских вариантов трихофитии? Клиническая дерматология и венерология. 2023; 22 (2): 141–146.

27. Pchelin I.M., Sergeev A.Yu. Drug resistance of dermatophytes: are we at risk of the emergence of Indian variants of trichophytosis? Clinical dermatology and venereology. 2023; 22 (2): 141–146. (In Russ.).

28. Mukherjee P.K., Leidich S.D., Isham N., Leitner I., Ryder N.S., Ghannoum M.A. Clinical Trichophyton Rubrum Strain Exhibiting Primary Resistance to Terbinafine. Antimicrobial Agents and Chemotherapy. 2003; 47 (1): 82–86. DOI: 10.1128/AAC.47.1.82–86.2

29. Тамразова О.Б. Наружные антимикотики в терапии поверхностных микозов кожи. Клинический разбор в общей медицине. 2024. Т. 5. № 6. С. 82–88.

30. Tamrazova O.B. External antifungals in the treatment of superficial mycoses of the skin. Clinical review in general medicine. 2024. Vol. 5. No. 6. P. 82–88. (In Russ.).

31. Singh A., Masih A., Monroy Nieto J., Singh P.K., Bowers J., et al. A unique multidrug resistant clonal Trichophyton population distinct from Trichophyton mentagrophytes/Trichophyton interdigitale complex causing an ongoing alarming dermatophytosis outbreak in India: Genomic insights and resistance profile. Fungal Genetics and Biology. 2019;133103266. https://doi.org/10.1016/j.fgb.2019.103266

32. Shen J.J., Arendrup M.C., Verma S., Saunte D.M.L. The Emerging Terbinafine Resistant Trichophyton Epidemic: What Is the Role of Antifungal Susceptibility Testing? Dermatol. Basel Switz. 2022; 238: 60–79. https://doi.org/10.1159/000515290

33. Taghipour S., Shamsizadeh F., Pchelin I.M., Rezaei Matehhkolaei A., Mahmoudabadi A.Z., et al. Emergence of Terbinafine Resistant Trichophyton mentagrophytes in Iran, Harboring Mutations in the Squalene Epoxidase (SQLE) Gene. Infection and Drug Resistance. 2020; 13: 845–850. DOI: 10.2147/IDR.S246025 30.

34. Pashootan N., Shams Ghahfarokhi M., Chaichi Nusrati A., Salehi Z., Asmar M., Razzaghi Abyaneh M. Phylogeny, Antifungal Susceptibility, and Point Mutations of SQLE Gene in Major Pathogenic Dermatophytes Isolated from Clinical Dermatophytosis. Frontiers in Cellular and Infection Microbiology. 2022; 12: 851769. DOI: 10.3389/fcimb.2022.851769.

35. Tang C., Kong X., Ahmed S.A., Thakur R., Chowdhary A., et al. Taxonomy of the Trichophyton mentagrophytes /T. interdigitale species complex harboring the highly virulent, multiresistant genotype T. indotineae. Mycopathologia. 2021; 186 (3): 315–326. https://doi.org/10.1007/s11046–021–00544–2/