Whole-genome resequencing of Trichophyton rubrum provides insights into population differentiation and drug resistance

  • Hailin Zheng
  • Oliver Blechert
  • Huan Mei
  • Liyu Ge
  • Jia Liu
  • Ye Tao
  • Dongmei Li
  • G. S. de Hoog
  • Weida LiuEmail author
Original Article


Trichophyton rubrum (T. rubrum) is anthropophilic fungus and thus a very common cause of dermatophyte infections around the world. Infection of T. rubrum could result in conditions such as tinea capitis, tinea corporis, tinea inguinalis, tinea manus, tinea unguium, or tinea pedis. Because of this, the resistance of T. rubrum to antifungal therapies has drawn extensive research interest. However, the pathogenic characteristics of T. rubrum, such as site of infections, geographic location and host groups, have yet to be explored. In this study, the whole genome of 48 strains from different regions is resequenced and the population structure and association of single nucleotide polymorphism with resistance to six widely used antifungal drugs are analyzed. A total of 23,394 genomic variations are detected, which cover 2165 genes with only 15.14% of the variations located in exons. The population structure of T. rubrum is monomorphic, and genetic diversity is very low. Population structure analysis shows that the 48 sampled strains can be divided into two sub-populations. The gene TERG_08771 harboring the highest SNPs density is found to be associated with resistance to voriconazole. Although many proteins have yet to be identified and explored, association studies could still be useful to identify drug resistance or drug-susceptible loci, which would warrant further insightful investigations.


T. rubrum Dermatophyte Resistance Population structure 



This work was financially supported by The National Natural Science Foundation of China (No. 81972949), The Scientific and Technological Innovation Projects of Medicine and Health of Chinese Academy of Medical Sciences (2016-I2M-3-021), The Basic Scientific Research Fund Projects of Chinese Academy of Medical Sciences (No. 2018PT31013), The Basic Scientific Research Fund Projects of Chinese Academy of Medical Sciences (Young Teacher foundation, No. 3332018121), and The subitem of the Important and Special Project of the Science and Technology Ministry of China (No. 2018ZX10734404).

Author contributions

HZ and WL conceived the ideas; HM, LG, and JL collected the data; OB, YT, HZ, and GSdeH analyzed the data; HZ and DL led the writing.

Compliance with ethical standards

Conflict of interest

The authors declare no competing financial interest.

Supplementary material

11046_2019_384_MOESM1_ESM.txt (1 kb)
Supplementary Code 1 The scripts pipeline for re-sequencing data handling in this study. There are 4 main steps including NGS data quality controlling, reads mapping, mapping stat calculation and SNP calling (TXT 1 kb)
11046_2019_384_MOESM2_ESM.txt (3 kb)
Supplementary Code 2 This is the PERL script for mapping stat calculation including sequencing depth and coverage (TXT 3 kb)
11046_2019_384_MOESM3_ESM.xls (1 mb)
Supplementary Table 1 The EggNOG-mapper re-annotated results for each gene models (XLS 1058 kb)
11046_2019_384_MOESM4_ESM.xlsx (12 kb)
Supplementary Table 2 The re-sequencing mapping results (XLSX 11 kb)
11046_2019_384_MOESM5_ESM.xls (17.9 mb)
Supplementary Table 3 Population-level SNPs results for 48 samples. “–” means genotype missingin corresponding loci (XLS 18319 kb)
11046_2019_384_MOESM6_ESM.xls (1.7 mb)
Supplementary Table 4 Population-level InDels results for 48 samples. “–” means genotype missing in corresponding loci (XLS 1736 kb)


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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Hailin Zheng
    • 1
    • 7
  • Oliver Blechert
    • 1
  • Huan Mei
    • 1
  • Liyu Ge
    • 1
  • Jia Liu
    • 1
  • Ye Tao
    • 3
  • Dongmei Li
    • 4
  • G. S. de Hoog
    • 5
    • 6
  • Weida Liu
    • 1
    • 2
    • 7
    Email author
  1. 1.Department of Medical Mycology, Institute of DermatologyChinese Academy of Medical Science and Peking Union Medical CollegeNanjingPeople’s Republic of China
  2. 2.Center for Global Health, School of Public HealthNanjing Medical UniversityNanjingChina
  3. 3.Shanghai Biozeron Biotechnology Co., LtdShanghaiChina
  4. 4.Department of Microbiology and ImmunologyGeorgetown University Medical CenterWashingtonUSA
  5. 5.Westerdijk Fungal Biodiversity InstituteUtrechtThe Netherlands
  6. 6.Institute of Biodiversity and Ecosystem DynamicsUniversity of AmsterdamAmsterdamThe Netherlands
  7. 7.Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIsNanjingChina

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