Cryptococcus neoformans urease affects the outcome of intracellular pathogenesis by modulating phagolysosomal pH.

摘要: Cryptococcus neoformans is a facultative intracellular pathogen and its interaction with macrophages key event determining the outcome of infection. Urease major virulence factor in C. but role during macrophage has not been characterized. Consequently, we analyzed effect urease on fungal-macrophage using wild-type, urease-deficient urease-complemented strains neoformans. The frequency non-lytic exocytosis events was reduced absence urease. Urease-positive manifested delayed replication fewer displaying phagolysosomal membrane permeabilization. production associated increased pH, which turn growth urease-positive inside macrophages. Interestingly, ure1 mutant strain grew slower fungal medium buffered to neutral pH (pH 7.4). Mice inoculated carrying had lower burden brain than mice infected wild-type strain. In contrast, did affect survival yeast when interacting amoebae. Because inability deletion grow urea as sole nitrogen source, hypothesize plays nutritional involved acquisition environment. Taken together, our data demonstrate that affects fitness within mammalian phagosome, promoting while delaying thus reducing damage, could facilitate cryptococcal dissemination transported This system provides an example where enzyme nutrient modulates