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

Abstract 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 tuberculosis 1-3 . 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.