Aspergillus fumigatus hijacks human p11 to redirect fungal-containing phagosomes to non-degradative pathway.

The decision whether endosomes enter the degradative or recycling pathway in mammalian cells is of fundamental importance for pathogen killing, and its malfunctioning has pathological consequences. We discovered that human p11 is a critical factor for this decision. The HscA protein present on the conidial surface of the human-pathogenic fungus Aspergillus fumigatus anchors p11 on conidia-containing phagosomes (PSs), excludes the PS maturation mediator Rab7, and triggers binding of exocytosis mediators Rab11 and Sec15. This reprogramming redirects PSs to the non-degradative pathway, allowing A. fumigatus to escape cells by outgrowth and expulsion as well as transfer of conidia between cells. The clinical relevance is supported by the identification of a single nucleotide polymorphism in the non-coding region of the S100A10 (p11) gene that affects mRNA and protein expression in response to A. fumigatus and is associated with protection against invasive pulmonary aspergillosis. These findings reveal the role of p11 in mediating fungal PS evasion. [Display omitted] • The human p11 protein is a regulatory node of phagosome maturation • The HscA protein of Aspergillus fumigatus anchors p11 on phagosomal membranes • p11 redirects phagosomes to the non-degradative pathway, allowing escape of conidia • A single nucleotide polymorphism (SNP) in the p11 gene is associated with susceptibility to invasive aspergillosis Jia et al. discover a mechanism allowing the human-pathogenic fungus A. fumigatus to escape intracellular killing by human cells. The authors identify the p11 protein as a regulatory node of phagosome maturation that is targeted by A. fumigatus. An SNP in the p11 gene is associated with invasive aspergillosis susceptibility. [ABSTRACT FROM AUTHOR]