Identification of novel inhibitors against Med15a KIX domain of Candida glabrata.

Candida glabrata, the second most common cause of invasive fungal infections, exhibits multi-drug resistance to commonly used antifungal drugs. To counter this resistance, there is a critical need for novel antifungals. This study identifies small molecule inhibitors that target a three-helix bundle KIX domain in the Med15a Mediator subunit of Candida glabrata (CgMed15a KIX). This domain plays a crucial role by interacting with the Pleiotropic Drug Resistance transcription factor Pdr1, a key regulator of the multidrug resistance pathway in Candida glabrata. We performed high throughput computational screening of large chemical datasets against the binding sites of the CgMed15a KIX domain to identify novel inhibitors. We selected six potential candidates with high affinity and confirmed their binding with the CgMed15a KIX domain. A phytochemical compound, Chebulinic acid binds to the CgMed15a KIX domain with a KD value of 0.339 µM and shows significant inhibitory effects on the growth of Candida glabrata. Molecular dynamics simulation studies further revealed the structural stability of the CgMed15a KIX-Chebulinic acid complex. Thus, in conclusion, this study highlights Chebulinic acid as a novel potential antifungal compound against Candida glabrata.

N-acetylglucosamine: a behavioral fate switch in Candida albicans.

Candida albicans, a significant commensal fungus in the human gut, causes a wide spectrum of opportunistic infections. In a recent study, Yang et al. revealed the importance of a host-associated gut signal, GlcNAc, in C. albicans and described its significant role towards achieving a successful commensal-virulence trade-off program in the human body.

Starch-lipid interaction alters the molecular structure and ultimate starch bioavailability: A comprehensive review.

Starch bioavailability which results in eliciting postprandial glycaemic response, is a trait of great significance and is majorly influenced by the physical interaction among the matrix components governed by their molecular structure as well as dynamics. Among physical interactions limiting starch bioavailability, starch and any guest molecules like lipid interact together to alter the molecular structure into a compact V-type arrangement endorsing the processed crystallinity, thus limiting carbolytic enzymatic digestion and further bioavailability. Considering the importance of starch-lipid dynamics affecting bioavailability, intensive research based on endogenous (internal lipids which are embedded into the food matrix) as well as exogenous (those are added from outside into the food matrix during processing like cooking) lipids have been carried out, endorsing physical interactions at colloidal and microstructural levels. The shared insights on such binary (starch-lipid) interactions revealed the evolution of characterization techniques as well as their role on altering the functional and nutritional value. It is very much vital to have a thorough understanding about the mechanisms on the molecular level to make use of these matrix interactions in the most efficient way, while certain basic questions are still remaining unaddressed. Do starch - lipid complexation affects the ultimate starch bioavailability? If so, then whether such complexation ability depends on amylose - fatty acid/lipid content? Whether the complexation is influenced further by fatty acid type/concentration/chain length or saturation? Further comprehending this, whether the altered bioavailability by binary (starch-lipid) could further be affected by ternary (starch-lipid-protein) and quaternary (starch-lipid-protein-phenolics) interactions are also discussed in this comprehensive review.

Cooking fat types alter the inherent glycaemic response of niche rice varieties through resistant starch (RS) formation.

Studies over the decades highlighted the role of lipids in modulating inherent glycaemic response of rice, still much needed to elucidate how the chain length and saturation of fatty acid (FA) influence this. Hence in this study, we investigated the in vitro glycaemic response, starch-lipid complexing ability and resistant starch (RS) formation in three rice types [white rice (WR), black rice (BR) and red rice (RR)] cooked with four fats [ghee, coconut oil (CO), virgin coconut oil (VCO) and rice bran oil (RBO)], with three cooking conditions ('before', 'during' and 'after'). Inherent glycaemic response was found least in RR (81.9%) and among the fats used, RBO rich in long chain unsaturated FA (72.6%) further reduced the least glycaemic response with maximum complexing ability and enriched RS content. Cooking conditions also resulted significant variation in the parameters studied, the most significant effect with complexing ability (28.67%) and RS (2.26%) observed when RBO added 'during' with RR. FTIR fingerprint within 950 to 1200 cm-1 region validated the complex interactions of amylose among FA, alcohols and acids present in the RBO. This is the first report proposing a 'lipid induced resistance towards glycaemic response' model highlighting the importance of FA type towards modulating the molecular configuration, complexing ability and RS-V formation.