Retrospective Epidemiological Study Of Dermatophytosis In China And Pathogenic Differences Between Trichophyton Rubrum And Trichophyton Violaceum

Part I Retrospective epidemiological analysis of dermatophytosis in ChinaBackground:Superficial mycosis is the most common fungal infection.Its epidemiology varies in different countries and regions,and its prevalence in China is still unknown.Objectives:We aimed to reveal the epidemiological features of dermatophytosis,the most common of superficial mycosis,and the onychomycosis,the fastest-growing incidence of superficial mycosis in Chinese mainland in the past thirty years.Methods:From 1991 to 2020,a 30-year retrospective epidemiological study was carried out.All published literatures containing dermatophytosis and onychomycosis were collected and analyzed.Results:(1)A total of more than 180,000 cases of dermatophytosis in 124 articles from more than 100 hospitals were included and analyzed.Among dermatophytosis,tinea cruris(24.92%)was the predominant clinical type,followed by tinea pedis(22.97%)and tinea corporis(18.12%).In recent 10 years,tinea pedis(25.40%)was more common than tinea cruris(22.39%)and became the most common infection.Among dermatophytes,T rubrum(69.48%)has always been the most common isolates,followed by T mentagrophytes(16.45%)and M canis(8.09%).Other species were found below 3%.In superficial mycoses,dermatophytes accounted for 75.52%,higher than that of yeasts/yeast-like(21.83%)and moulds(2.65%).The prevalence of tinea capitis was lower in economically developed eastern region than that in central and western regions.Tinea cruris was more common in warm zones than cold zones.(2)A total of 90 articles involving more than 40,000 onychomycosis patients were enrolled in this study.We found dermatophytes(60.59%)were the most frequently isolated pathogens,followed by yeasts(30.09%),molds(7.91%)and mixed infection(1.41%).The primary pathogens in dermatophytes,yeasts and molds were Trichophyton rubrum(79.31%),Candida albicans(36.58%)and Aspergillus(44.44%),respectively.Additionally,dermatophytes were more commonly affected males than females(63.69%vs.51.57%),and mostly involved in toenail onychomycosis(75.63%).The infection of yeasts was high in females(40.97%),often causing onychomycosis in fingernail than toenail(41.03%vs.17.08%),and it is more common in warm and humid southern regions than north regions(34.07%vs.24.41%).Conclusions:The top three dermatophytoses are tinea cruris,tinea pedis and tinea corporis,while the top three dermatophytes are T rubrum,T mentagrophytes and M canis.Dermatophytes,especially Trichophyton rubrum have always been the principal pathogen in onychomycosis,followed by yeasts and molds.Socioeconomic status,geographical-meteorological conditions,sex and infection site all have a clear influence on the distribution of fungal pathogens.Part II Pathogenic differences between Trichophyton rubrum and Trichophyton violaceumBackground:Trichophyton rubrum and Trichophyton violaceum shared high collinearity at the nucleotide level,with 99.38%identity,but they are varied widely in epidemiology,phenotype and clinical manifestations.Objectives:We aimed to compare the DNA methylation profiles between T.rubrum and T.violaceum and explored the differences between them,and further identify the effect of DNA methylation on the transcriptional level.Methods:Whole-genome bisulfite sequencing and RNA sequencing were used to investigate the genome-wide DNA methylation patterns and the RNA transcriptional level respectively.Results:This study revealed the global DNA methylation pattern of T.rubrum and T.violaceum,and the methylation level of T.rubrum was higher than that of T.violaceum.A total of 681 differentially methylated regions were identified between the two groups,which corresponded to 357 differentially methylated genes.Compared with T.rubrum,466 of them were hypermethylating,and 215 were hypomethylating.At the transcriptional level,a total of 1050 differentially expressed genes were identified,among which,755 genes were up-regulated and 295 were down-regulated in T.violaceum.Gene ontogeny and KEGG pathway analyses indicated that these were mainly involved in the production of metabolites and energy metabolism pathways.There were 11 differentially identical genes in methylation and transcriptome,which were involved in the growth,metabolism,virulence and drug resistance of strains.Conclusion:There are differences in DNA methylation modification between T.rubrum and T.violaceum in terms of growth,metabolism,virulence and drug resistance of the strains,and affect transcriptional regulation,resulting in the difference of phenotype and pathogenicity of them.