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The ability to suppress the immune system has lead to great advances in transplant technology and treatment of autoimmune diseases. Unfortunately, the immunosuppression of these patients has led to the rise of opportunistic infections by organisms that are recalcitrant to current prophylactic strategies. One such example is the increase of mucormycosis, an invasive infection caused by filamentous fungi of the order Mucorales. In this issue of the JCI, Gebremariam and colleagues determined that spore coat homolog (CotH) proteins are required for angioinvasion and that these proteins are unique to Mucorales. Their findings provide a potential therapeutic target for prevention and treatment of mucormycosis.