Evolution of the ability to evade host innate immune defense by Talaromyces marneffei

Abstract

Talaromyces (Penicillium) marneffei is an intracellular pathogenic fungus. Some strains of this fungus have been misidentified due to the similarity between Talaromyces and Penicillium. T. marneffei has mainly been found to afflict immunocompromised individuals, causing respiratory, skin, and systemic mycosis. Mp1p is a key virulence factor that can help T. marneffei evade clearance by the normally functioning immune system. Understanding how novel functions arise is an intriguing question in many fields of biology. Mp1p has two homologous domains (Mp1p-LBD1 and Mp1p-LBD2). Sequence similarity searches with Mp1p-LBD sequences revealed Mp1p homologs in many other pathogenic fungi. Integrated information on the taxonomic distribution, phylogenetic relationships, and sequence similarity of Mp1p domains revealed that the ancestor of Mp1p-LBDs was acquired through horizontal gene transfer (HGT). Additional evidence revealed that Mp1p homologs have undergone extensive gene duplications in T. marneffei. Mp1p might be a result of gene fusion following gene duplication. Furthermore, we propose a new method for identifying Talaromyces and identify 4 strains with misclassification errors. Our results characterize the evolutionary mechanism of T. marneffei evasion of host innate immune defense and clearly demonstrate the role of gene duplication and HGT in the evolution of host immune escape by T. marneffei.