Membrane Integrity Contributes to Resistance of Cryptococcus neoformans to the Cell Wall Inhibitor Caspofungin
Brenda Moreira-Walsh, Abigail E. Ragsdale, Woei C. Lam, Rajendra Upadhya, Evan Xu, Jennifer K. Lodge, Maureen J. Donlin
Abstract
The intrinsic resistance of Cryptococcus neoformans to the cell wall inhibitor caspofungin limits the available therapies for treating cryptococcal infections. We screened a collection of more than 4,000 gene deletion strains for altered caspofungin sensitivity to identify biological processes that could be targeted to render the cell more susceptible to caspofungin. We identified multiple genes with an effect on caspofungin susceptibility and found that they were associated with altered membrane permeability rather than the expected cell wall defects. This suggests that targeting these genes or other genes affecting membrane permeability is a viable path for developing novel therapies for treating this global fungal pathogen.