Myxococcus xanthus, a nonpathogenic bacterium, eliminates Cryptococcus neoformans, a fungal pathogen of human, independent of cell-cell contact

Each year an estimated 1.2 billion people suffer from fungal diseases and 1.5 - 2 million die from fungal infections - surpassing the loss from malaria and tuberculosis1-3. Due to the similarities between fungal and human cells, the lack of fungal-specific targets has become the major hurdle for antifungal discovery. Many fungi, including the deadly human pathogen Cryptococcus neoformans, are found in soil, where they compete with other microorganisms, including bacteria. However, most bacteria that inhibit fungal growth are pathogens and their antifungal effects strictly rely on cell-cell contact. Here we show that Myxococcus xanthus, a nonpathogenic, soil-dwelling bacterium, efficiently eliminates C. neoformans and strongly inhibits the production of fungal virulence factors. Remarkably, these antifungal activities do not require cell-cell contact. Using fluorescence microscopy, we found that M. xanthus increases the permeability of C. neoformans cells. Our results on the cross-kingdom interaction between M. xanthus and C. neoformans will reveal fundamental mechanisms for bacterial-fungal interactions and suggest novel strategies for antifungal therapies.