pH manipulation as a novel strategy for treating mucormycosis

Mucormycosis is a fatal fungal disease caused by several organisms within the order Mucorales. In recent years, traumatic injury has emerged as a novel risk factor for mucormycosis. Current antifungal therapy is ineffective, expensive, and typically requires extensive surgical debridement. There is thus a pressing need for safe prophylactic treatment that can be rapidly and easily applied to high-risk patients, such as those with major trauma injuries. Acetic acid has been used as a topical treatment for burn wounds for centuries and has proven activity against Gram-negative bacteria. Here, we demonstrate that acetic acid is also highly effective against major pathogenic groups of Mucorales, even at very low concentrations (0.3%). This antifungal effect is not seen with other acids, such as hydrochloric and lactic acid, suggesting that acetic acid activity against Mucorales spores is not solely evoked by low environmental pH. In agreement with this, we demonstrate that the antifungal activity of acetic acid arises from a combination of its ability to potently lower intracellular pH and from pH-independent toxicity. Thus, dilute acetic acid may offer a low-cost, safe, prophylactic treatment for patients at risk of invasive mucormycosis following traumatic injury.