Intraspecific Variations and Characteristics of Clinical, Physiological, and Antifungal Susceptibility Profiles of Trichophyton rubrum in Southwest China.

To date, research on the efficacy of intraspecific molecular markers for the clonal fungal species Trichophyton rubrum, particularly studies that validate these markers through phenotypic characterization, has remained extremely limited. This study re-evaluated and confirmed the population structure of T. rubrum in southwestern Guizhou, China, by employing both the terg_02941 gene-encoding a protein of unknown function-and the conventional molecular marker rpb2. Integrated analyses incorporating clinical, physiological, and antifungal susceptibility data were conducted to investigate potential associations between distinct genetic lineages and their corresponding phenotypes. Phylogenetic analysis based on terg_02941 classified 324 Guizhou isolates into two major genetic lineages: ST1 (166 isolates) and ST2 (158 isolates), with ST1 forming a distinct lineage supported by moderate bootstrap values. In the rpb2-based phylogeny, two Guizhou isolates harboring non-synonymous mutations clustered within the ST1 group as a separate sublineage, further supporting the genetic stability or adaptive advantage of the ST1 population. Clinically, the ST1 lineage exhibited reduced prevalence among individuals under 15 years and over 60 years of age and showed diminished colonization of the human body's midline anatomical sites (P < 0.01). Physiologically, the ST1 population demonstrated lower tolerance to low temperature and acidic conditions. Notably, colonies of the ST1 lineage lacked red pigment production and predominantly exhibited yellow pigmentation (P < 0.001). Although no significant differences were observed in the geometric mean MIC values or the proportion of non-wild-type strains between the two lineages, pigment formation was negatively correlated with the degree of antifungal resistance (DDR) (P < 0.001), with classical red-pigmented strains showing the highest frequency of susceptibility. Collectively, the two globally distributed genetic lineages of T. rubrum in Guizhou exhibit both shared polymorphic traits and lineage-specific phenotypic tendencies. The more stable ST1 lineage appears to have achieved persistent colonization of human skin through a process of phenotypic streamlining, whereas the ancestral ST2 lineage displays broader phenotypic diversity, offering potential evidence for an ecological transition from environmental reservoirs to human host adaptation.