Pathogenic strategies of <i>Pseudogymnoascus destructans</i> during torpor and arousal of hibernating bats.

Abstract

Millions of hibernating bats across North America have died from white-nose syndrome (WNS), an emerging disease caused by a psychrophilic (cold-loving) fungus, <i>Pseudogymnoascus destructans</i>, that invades their skin. Mechanisms of <i>P. destructans</i> invasion of bat epidermis remain obscure. Guided by our in vivo observations, we modeled hibernation with a newly generated little brown bat (<i>Myotis lucifugus</i>) keratinocyte cell line. We uncovered the stealth intracellular lifestyle of <i>P. destructans</i>, which inhibits apoptosis of keratinocytes and spreads through the cells by two epidermal growth factor receptor (EGFR)-dependent mechanisms: active penetration during torpor and induced endocytosis during arousal. Melanin of endocytosed <i>P. destructans</i> blocks endolysosomal maturation, facilitating <i>P. destructans</i> survival and germination after return to torpor. Blockade of EGFR aborts <i>P. destructans</i> entry into keratinocytes.