| Dermatophytosis is the most common fungal infectious disease in clinics, which usually invade skin and related appendages. This PhD thesis focuses on two topics involved in dermatophytes infections:(1) comparative analysis of 9 dermatophytes genomes including 8 most common pathogenic species, to analyze genome characteristics, biological function and possible virulence factors of Trichopyton rubrum complex; And (2) as tinea capitis is one kind of dermatophytes infection with clinical profiles and the spectrum of etiological agents varying with geographic and history context, epidemiology changes in tinea capitis during the past 60 years of economic growth in China were analyzed by a literature review.Chaptr 1 Comparative genome analysis of dermatophytes:biological and pathological mechanisms of Trichopyton rubrum complexOne clinical srain of T. rubrum CMCC(F)TLi isolated from onychomycosis and one strain of T. violaceum CMCC(F)T31 isolated from tinea capitis were whole genome sequenced by Illumina/Solexa, while the former was sequenced by Pacific Biosciences sequencing simultaneously. The two genomes were compared to each other, as well as the other 7 dermatophytes genomes (T. rubrum CBS 118892,T. tonsurans CBS 112818, Arthroderma gypseum CBS 118893、Microsporum canis CBS 113480, Trichophyton equinum CBS127.97, Arthoderma benhamiae CBS 112371 and Trichophyton verrucosum HKI0517)and 12 non-dermatophytes fungi (Aspergillus fumigatus AF 293-. Aspergillus nidulans FGSC A4、Coccidioides immitis RS, Paracoccidioides brasiliensis Pb18, Histoplasma capsulatum H88, Blastomyces dermatitidis ATCC 18188, Cryptococcus neoformans JEC21, Malassezia globosa CBS 7966, Malassezia sympodialis ATCC 42132, Candida albicans WO-1, Saccharomyces cerevisiae S288c, Schizosaccharomycespombe 972h). We focused on the pathogenic related factors, such as adhesins, secreted proteinases, mating control locus, to explore the genome structure, biology, metabolism and pathogenicity of Trichophyton rubrum complex.The third-generation sequencing technique can supply long, perfect sequences, as well as full mitochondrial structure. Trichophyton rubrum and T. violaceum show a quite high genome similarity and synteny, with 99.38% identity at nucleic acid level. As for genes, there were only 18 different CDS together. The two dermatophytes have similar mating tye locus, displayed as MAT1-1 type (alpha-box). The genome comparison analysis showed that dermatophytes geneome are highly conservative with few repeat elements. Multiply proteinase family expanded, e.g M35, M36 and S8A family. On the phylogeny trees, all the proteinases are conservative in copies and sequences despite of specificity among species. T. rubrum and T.violaceum, T. tonsurans and T.equinum, T.verrucosum and A. benhamiae are highly identical, respectively. M. gypseum and M. canis are a little far away. About twenty to thirty adhesins are predicted in anthropophilic and zoophilic species, while only 5 in geophilic species. Secreted proteases, adhesion factors are supposed to be responsible for the difference in invasion of dermatophytes and variable immune reaction with host.Chapter 2 Tinea capitis in the Nanchang area, Southern China:a fifty-year survey (1965-2014)Qingyunpu district, suburban area of Nanchang, used to be hyper-endemic for favus in 1950s and 1960s. As a result of governmental programs in treatment, prevention of tinea capitis and social development, favus has been successfully controlled in this region by 1980s. In this study, three community surveys and a retrospective study were carried out during the past 50 years (1965-2014) in Qingyunpu District. Clinical presentation and spectrum of etiological agents were tracked to understand the evolution of tinea capitis.Favus was highly epidemic in this study site, with a prevalence of 3.41% in 1965, while the prevalence decreased to less than 0.01% in 1977. After that period, clinical presentation and spectrum of fungi in tinea capitis shift with the social development. The causative agent, Trichophyton scholeinii has been replaced by T. violaceum (68.9%), followed by T. mentagrophtes compex (14.3%), T. tonsurans (7.2%) and few other species. Trichophyton violaceum is corresponding with a dominant black dot type of tinea capitis in the Nanchang area.Chapter 3 Epidemiological changes in tinea capitis during sixty years of economic growth in ChinaWe queried Pubmed (http://www.ncbi.nlm.nih.gov/pubmed/), WanFang (http://www.wanfangdata.com.cn/), WeiPu (http://www.cqvip.com/) and CKNI (http://www.cnki.net/) for all publications about tinea capitis between 1956 and 2014 in which the pathogens were identified either by morphological or molecular methods. The disease pattern was correlated with economic and public health management protocols. Historical data on fungal identification were mostly obtained by morphology. The accuracy of these historical results was further confirmed by use of both morphological and ITS identification on a control set of 90 isolates collected recently from local hospitals.Full agreement of the two identification methods implied that data from the literature were sufficiently reliable to allow comparison across reported cases. In sum,88 papers involving 25 administrative provinces and municipalities with 38,962 clinical strains met the inclusion criteria of this review. Zoophilic species Microsponim canis is the most prevalent agent within large, modernized cities in China today accounting for over 80% of infections. In contrast, anthropophilic dermatophytes, particularly Trichophyton violaceum, are geographically endemic only in some southeastern and northwestern regions. Economic development and urbanization of cities favor a shift of etiological agents from anthroponoses to zoonoses in contemporary China. Pets are becoming the most likely sources of infection in modern lifestyles, replacing the earlier human-to-human transmission mode. However, the latter transmission mode is still prevalent in less developed areas lacking adequate social and public health facilities. |
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