Aureoverticillactam, a Potent Antifungal Macrocyclic Lactam from Streptomyces aureoverticillatus HN6, Generates Calcium Dyshomeostasis-Induced Cell Apoptosis via the Phospholipase C Pathway in Fusarium oxysporum f. sp. cubense Race 4

Abstract

Extensive efforts have been devoted to discover new bio-fungicides of high efficiency for control of Fusarium oxysporum f. sp. cubense race 4 (Foc4), a catastrophic soil-borne phytopathogen causing banana fusarium wilt worldwide. In this paper, aureoverticillactam (YY3) was verified to possess a potent antifungal activity against Foc4 for the first time, with the EC50 values of 20.80 μg/ml against hyphal growth, and 12.62 μg/ml against spore germination. To provide insight into its action mechanism, the cellular ultrastructures of Foc4 was observed with YY3 treatment and the results revealed that YY3 led to cell wall thinning, mitochondrial deformities, apoptotic degradation of the subcellular fractions and entocyte leakage. Consistent with these variations, the enhanced permeability of cell membrane and mitochondrial membrane also occurred after YY3 treatment. At the enzymatic level, the activity of mitochondrial complex III, as well as the ATP synthase, was significantly suppressed by YY3 at a concentration above 12.50 μg/ml. Moreover, YY3 elevated the cytosolic Ca2+ level to promote the mitochondrial ROS production. The cell apoptosis also occurred as expected. At the transcriptome level, key genes involved in phosphatidylinositol signaling pathway were significantly impacted, with the expression level of Plc1 elevated by approximately 4 folds. The expression levels of two apoptotic genes, casA1 and casA2, were also significantly elevated by YY3. Of note, the activation of phospholipase C was observed by YY3 treatment in Foc4. These findings indicate that YY3 exerts its antifungal activity via activating the phospholipase C-calcium-dependent ROS signaling pathway, which makes it a great potential bio-fungicide

Lipopeptide C17 Fengycin B Exhibits a Novel Antifungal Mechanism by Triggering Metacaspase-Dependent Apoptosis in Fusarium oxysporum

“…displayed similar ROS-mediated mitochondrial apoptotic phenotypes in F. oxysporum induced by cinnamaldehyde or aureoverticil lactam. , Kai et al showed that chlorogenic acid inhibits Fusarium fujikuroi growth by triggering cellular ROS accumulation, thereby further inducing cell apoptosis in this pathogen . Liang et al reported that surfactin displays antifungal activity against F.…”

Modeling Calcium Signaling in S. cerevisiae Highlights the Role and Regulation of the Calmodulin-Calcineurin Pathway in Response to Hypotonic Shock

“…Being Ca 2+ an essential signaling ion, proteins involved in its homeostasis are increasingly studied as potential targets of antifungal drugs ( Kwun et al, 2021 ; Li et al, 2021 ; Wang et al, 2021 ). A model of Ca 2+ signaling could be used to predict the outcomes of the inhibition of a particular protein on the calcium physiology of fungal cells, thus helping to identify the best drug targets.…”

Preparation, biocontrol activity and growth promotion of biofertilizer containing Streptomyces aureoverticillatus HN6

“…In that order, 1 mL of supernatant was diluted to 10 -7 , 10 -8 , and 10 -9 . Aliquots of 25 μL were spread onto Koch’s One solid medium using a bent rod ( Wang et al., 2021b ). The culture was spread evenly and incubated for 5 d at 28°C.…”

“…Chlorophyll content, root vigor, soluble reducing sugar content, soluble protein content, catalase activity, and free amino acid content of cowpea seedlings were determined using the plant chlorophyll content test kit from Beijing Solabao Technology Co Ltd. Previously reported method were followed for TTC ( Zhang et al., 2015 ), anthrone colorimetric, UV absorption and potassium permanganate titration ( Wang et al., 2021b ), ninhydrin color development ( Lu and Mallette., 1970 ).…”