Cryptococcus at Work: Gene Expression during Human Infection

ABSTRACT Meningitis is a frequent manifestation of infection due to Cryptococcus neoformans and a major cause of increased morbidity in patients with AIDS. Numerous in vitro gene expression and genetic studies of the fungus have predicted a myriad of genes, pathways, and biological processes that may be critical for pathogenesis, andmany studies using animal models have supported the role of these processes during infection. However, the relevance of these hypotheses based on in vitro and animal models has often been questioned. A recent study by Chen et al. [Y. Chen, D. L. Toffaletti, J. L. Tenor, A. P. Litvintseva, C. Fang, T. G. Mitchell, T. R. McDonald, K. Nielsen, D. R. Boulware, T. Bicanic, and J. R. Perfect, mBio 5(1):e01087-13, 2014] represents an important step in understanding the cryptococcal response during human infection. Cryptococcus neoformans is distributedworldwide, grows in soil,fends off a variety of phagocytic predators, and can infect a wide variety of animals and plants. The presence and survival of the fungus in these diverse environmental and host conditions imply that the fungus has evolved awell-orchestrated gene expres-sion program that enables it to adapt andproliferate under various conditions. The data from testing a multitude of genetic variants under defined in vitro growth conditions and in multiple animal infection models for C. neoformans have been used to formulat