Antifungal Lipopeptides

Antifungal Lipopeptides Fengycins are a class of antifungal lipopeptides synthesized by the bacteria Bacillus subtilis, commercially available as the primary component of the agricultural fungicide Serenade. They are toxic to fungi, but far less to mammalian cells. One key difference between mammalian and fungal cell membranes is the presence of cholesterol only in the former; recent experimental work showed that the presence of cholesterol reduces fengycin-induced membrane leakage. Since our previous all-atom and coarse-grained simulations suggested that aggregation of membrane-bound fengycin is central to its ability to disrupt membranes, we hypothesized that cholesterol might reduce fengycin aggregation. Here, we test this hypothesis using coarse-grained molecular dynamics simulations, with sampling enhanced via the weighted ensemble method. The results indicate that cholesterol subtly alters the size distribution for fengycin aggregates, limits the lateral range of their membrane disordering, and reduces the ability of aggregates to bend the membrane. Taken together, these phenomena may account for cholesterol’s effects on fengycin activity. The world human population has reached 7.8 billion as of August 2021, which creates ever greater pressure to increase agricultural yields. Every year crops are destroyed by various microbial infections, of which 60% are caused by fungus. To cope with this, various antibiotics have been synthesized like amphotericin B, natamycin and nystatin but fungi and bacteria are developing resistance to these compounds. Regards Alex John Editorial Assistant Clinical Toxicology