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Virulence pathways in pathogenic bacteria are regulated by quorum sensing mechanisms, particularly biofilm formation through autoinducer (AI) production and sensing. In this study, the culture filtrate extracted from an edible mushroom, Agaricus subrutilescens , was fractionated to isolate a compound that inhibits biofilm formation. Four gram-negative bacteria (Klebsiella pneumoniae, Escherichia coli, Proteus mirabilis , and Enterobacter cloacae) and two gram-positive bacteria (Enterococcus faecalis and Staphylococcus aureus) were used for the bioassay. The bioassay-guided chromatographic separations of the culture filtrate extract resulted in the isolation of the compound. Further, spectroscopic analyses revealed the identity of the compound as 2,2′-azoxybisbenzyl alcohol (ABA). The minimum inhibitory and sub-inhibitory concentrations of the compound were also determined. Azoxybisbenzyl alcohol was significantly effective in inhibiting biofilm formation in all tested bacteria, with half-maximal inhibitory concentrations of 3–11 µg/mL. Additionally, the bioactivity of ABA was confirmed through the bioassays for the inhibition of exopolysaccharide matrixes and AI activities. [ABSTRACT FROM AUTHOR]

The smoke from Combretum hartmannianum and Terminalia laxiflora sapwood and fermented heartwood (nikhra) are used in body smoke baths and homemade skincare products in Sudan, which are believed to have various health benefits. In this study, the volatiles of sapwood and nikhra were collected using two extraction techniques: a Mono-TrapTM sampling technique (at low temperature) and a smoke trapping system (at high temperature). After GC-MS analysis, the chromatogram of each sample revealed numerous peaks. The detected peaks were identified using the DIST08 mass spectral library database, resulting in known and unknown compounds. The results showed that 1,2,4,5-tetrachloro-3,6-dimethoxybenzene was the major compound in the Mono-Trap and smoke extracts from nikhra samples of C. hartmannianum and T. laxiflora. In contrast, the dominant compounds in the Mono-Trap extracts of C. hartmannianum and T. laxiflora sapwoods were acetonyldimethylcarbinol and cadina-1(10),4-diene, respectively. The largest peaks in the chromatograms of the sapwood smoke extracts of both species corresponded to unknown compounds. Some of the detected compounds are known for their aromatic and pharmaceutical properties. Identifying these aromatic compounds in nikhra and not in sapwood might prove the traditional Sudanese beliefs, and it could potentially improve the manufacturing of health products. [ABSTRACT FROM AUTHOR]

Purpose: Strobilurins act as antifungal agents by inhibiting the mitochondrial respiratory chain. The cytotoxic activity of strobilurins, focusing on its anticancer activities, has been reported. However, the mechanisms involved in these activities remain unclear. Methods: The cytotoxic effects of strobilurin X isolated from the mycelium of Mucidula. venosolamellata were examined in human cancer cell lines (A549 and HeLa) and normal fibroblasts (WI-38). Results: Strobilurin X significantly decreased the viability of A549 and HeLa cells compared to that in the WI-38 cells after 48 h of exposure. The EC50 values for cytotoxicity in the A549, HeLa, and WI-38 cells were 3.4, 5.4, and 16.8 μg/mL, respectively. Strobilurin X inhibited the mitochondrial respiratory chain and enhanced the release of lactate in the A549 cells. The IC50 value of strobilurin X against the mitochondrial respiratory chain complex III activity was 139.8 ng/mL. The cytotoxicity induced by strobilurin X was not completely rescued after adding uridine, methyl pyruvate, or N-acetyl cysteine. Furthermore, pharmacological approaches demonstrated that strobilurin X failed to modulate the mitogen-activated protein kinase family and phosphoinositide 3-kinase-Akt pathways; alternatively, it suppressed protein synthesis independent of uridine. Conclusion: Strobilurin X induced cytotoxicity by blocking the mitochondrial respiratory chain and suppressing protein synthesis. These findings may aid in the development of novel anticancer drugs using strobilurins. [ABSTRACT FROM AUTHOR]

Several recent studies describe the influence of the gut microbiota on host brain and behavior. However, the mechanisms responsible for microbiota-nervous system interactions are largely unknown. Using a combination of genetics, biochemistry, and crystallography, we identify and characterize two phylogenetically distinct enzymes found in the human microbiome that decarboxylate tryptophan to form the β-arylamine neurotransmitter tryptamine. Although this enzymatic activity is exceedingly rare among bacteria more broadly, analysis of the Human Microbiome Project data demonstrate that at least 10% of the human population harbors at least one bacterium encoding a tryptophan decarboxylase in their gut community. Our results uncover a previously unrecognized enzymatic activity that can give rise to host-modulatory compounds and suggests a potential direct mechanism by which gut microbiota can influence host physiology, including behavior.

Strobilurins A and X, isolated from Mucidula venosolamellata culture extracts, demonstrated potent inhibition of human melanoma G-361 cell proliferation. Strobilurin X exhibited milder inhibitory effects on human fibroblast cells (NB1RGB) compared to strobilurin A. Additional strobilurin-related compounds were isolated from the other mushroom species. Oudemansins A and B displayed weaker activities on G-361 cells than strobilurins A and B, respectively, emphasizing the importance of a conjugated double-bond structure. Among isolated compounds, strobilurin G showed the lowest IC50 value for G-361 cells. Additional strobilurins bearing various substituents on the benzene ring were synthesized. Synthetic intermediates lacking the methyl β-methoxyacrylate group and a strobilurin analogue bearing modified β-methoxyacrylate moiety showed almost no inhibitory activity against G-361 cells. The introduction of long or bulky substituents at the 4′ position of the benzene ring of strobilurins enhanced the activity and selectivity, suggesting differential recognition of the benzene ring by G-361 and NB1RGB cells. [ABSTRACT FROM AUTHOR]