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, Pseudogymnoascus destructans, that invades their skin. Mechanisms of P. destructans invasion of bat epidermis remain obscure. Guided by our in vivo observations, we modeled hibernation with a newly generated little brown bat (Myotis lucifugus) keratinocyte cell line. We uncovered the stealth intracellular lifestyle of P. destructans, 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 P. destructans blocks endolysosomal maturation, facilitating P. destructans survival and germination after return to torpor. Blockade of EGFR aborts P. destructans entry into keratinocytes.
摘要:
北美数以百万计的冬眠蝙蝠死于白鼻综合症(WNS),一种由嗜冷(嗜冷)真菌引起的新出现的疾病,假木曲菌破坏,侵入他们的皮肤。蝙蝠表皮破坏假单胞菌入侵的机制仍然不清楚。在我们体内观察的指导下,我们用新产生的小棕色蝙蝠(Myotislucifugus)角质形成细胞系模拟冬眠。我们发现了P.destructans的隐形细胞内生活方式,它通过两种表皮生长因子受体(EGFR)依赖性机制抑制角质形成细胞的凋亡并通过细胞传播:在torpor期间的主动渗透和在唤醒期间的诱导内吞作用。内吞破坏假单胞菌的黑色素阻断内溶酶体成熟,促进P.destructans的存活和发芽后返回到torpor。EGFR的阻断中止了P.破坏性蛋白进入角质形成细胞。