Montoya Marhiah C, Wilhoit Kayla, Murray Debra, Perfect John R, Magwene Paul M
Division of Infectious Diseases, Department of Medicine, Duke University, Durham, NC, USA.
University Program in Genetics and Genomics, Duke University, Durham, NC, USA.
Cell Rep. 2025 Aug 5;44(8):116103. doi: 10.1016/j.celrep.2025.116103.
Opportunistic microbial pathogens that infect humans must adapt to radically different fitness landscapes as they transition from the external environment to the host niche. The nature, frequency, and magnitude of genomic changes that accompany adaptation to the human host niche are not well understood for many eukaryotic pathogens because of the logistical challenges of obtaining longitudinal samples of pathogen populations in individual patients. Drawing on a set of case studies, we characterize in-host genomic and phenotypic evolution of the opportunistic human fungal pathogen Cryptococcus neoformans during chronic infections. We find that fungal genome evolution during chronic infection is characterized by large-scale genome restructuring and increasing genomic heterogeneity within hosts. Phenotypic changes include diversification in virulence traits and antifungal susceptibility. Genotypically and phenotypically distinct sublineages arise and co-persist within the same host tissues, consistent with a model of strong and/or diversifying selection in the complex environment of human hosts.
感染人类的机会性微生物病原体在从外部环境过渡到宿主生态位时，必须适应截然不同的适合度景观。由于获取个体患者病原体群体纵向样本存在后勤方面的挑战，许多真核病原体适应人类宿主生态位时伴随的基因组变化的性质、频率和幅度尚未得到很好的理解。基于一系列案例研究，我们描述了机会性人类真菌病原体新生隐球菌在慢性感染期间的宿主机内基因组和表型进化。我们发现，慢性感染期间真菌基因组进化的特征是大规模基因组重组以及宿主机内基因组异质性增加。表型变化包括毒力性状和抗真菌药敏性的多样化。基因型和表型不同的亚系在同一宿主组织内出现并共同存在，这与人类宿主复杂环境中强大的和/或多样化选择模型一致。
