Summary auto-generated
This study investigated whether Trichosporon asahii, an opportunistic fungal pathogen causing life-threatening infections in immunocompromised patients, undergoes phenotypic changes during infection. Researchers compared three environmental isolates with 14 clinical isolates from deep-seated infections and examined changes after three passages through immunosuppressed mice. Environmental isolates displayed rugose colonies and hyphal morphology, while clinical isolates showed powdery colonies and conidial forms. Notably, clinical isolates released significantly higher levels of glucuronoxylomannan (GXM) antigen, a known virulence factor that protects fungi from immune attack. When environmental isolates were serially passaged through mice, they underwent morphological transformation to resemble clinical isolates, with colonies changing from rugose to powdery type and cells converting from hyphae to conidia. Crucially, passaged isolates showed progressive increases in GXM antigen release with each passage. These findings suggest that in-vivo adaptation enables T. asahii populations to increase GXM production, facilitating escape from phagocytosis and establishment of persistent infections. This represents the first documented evidence of in-vivo phenotypic switching in Trichosporon species.
Key findings
- Environmental T. asahii isolates differ markedly from clinical isolates in colony morphology (rugose vs. powdery), cell type (hyphae vs. conidia), and GXM antigen production
- Environmental isolates passaged three times through immunosuppressed mice underwent phenotypic transformation to resemble clinical isolates, with morphological and antigenic changes
- Repeated in-vivo passage was associated with progressive, significant increases in GXM antigen release, a virulence factor protecting fungi from phagocytosis
- The phenotypic changes in passaged isolates were stable upon subculture and did not revert, suggesting in-vivo selection of new phenotypic variants
- This phenotypic switching mechanism may enable T. asahii populations to evade host immune defenses and establish persistent infections
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Abstract
Clinically important fungi such as Candida albicans and Cryptococcus neoformans are known to undergo phenotypic changes after repeated subculture or passages in vivo. However, there are no reports describing this phenomenon in Trichosporon species. This study investigated whether in-vivo passages of environmental isolates of Trichosporon asahii in mice changes their phenotype; three environmental isolates and 14 clinical isolates (from deep-seated infections) were used. The shape of the colony and cell type were observed, and the titre of glucuronoxylomannan (GXM) antigen and concentration of (13)-ß-D-glucan were measured for each isolate. Changes in these features were also examined after three passages of the environmental isolates in mice. The shape of colonies and cell types were clearly different in environmental and clinical isolates. Furthermore, the clinical isolates released significantly higher levels of GXM antigen than environmental isolates (titre: log2 9.4 SD 0.7 versus log2 5.4 SD 1.4). The phenotype of passaged isolates was significantly different from the original environmental isolates with respect to the morphology of colonies and cell type and GXM release (titre: log2 10.0 SD 0.7 versus log2 5.4 SD 1.4). These results suggest that the phenotypic changes in T. asahii occur as a result of in-vivo passages. This process may allow a proportion of the fungal population to escape eradication by the host immune system, as GXM antigen is considered to protect the fungi against phagocytosis by polymorphonuclear leucocytes and monocytes in vivo.