Unveiling the mysteries: Functional insights into hypothetical proteins from Bacteroides fragilis 638R.

Humans benefit from a vast community of microorganisms in their gastrointestinal tract, known as the gut microbiota, numbering in the tens of trillions. An imbalance in the gut microbiota known as dysbiosis, can lead to changes in the metabolite profile, elevating the levels of toxins like Bacteroides fragilis toxin (BFT), colibactin, and cytolethal distending toxin. These toxins are implicated in the process of oncogenesis. However, a significant portion of the Bacteroides fragilis genome consists of functionally uncharacterized and hypothetical proteins. This study delves into the functional characterization of hypothetical proteins (HPs) encoded by the Bacteroides fragilis genome, employing a systematic in silico approach. A total of 379 HPs were subjected to a BlastP homology search against the NCBI non-redundant protein sequence database, resulting in 162 HPs devoid of identity to known proteins. CDD-Blast identified 106 HPs with functional domains, which were then annotated using Pfam, InterPro, SUPERFAMILY, SCANPROSITE, SMART, and CATH. Physicochemical properties, such as molecular weight, isoelectric point, and stability indices, were assessed for 60 HPs whose functional domains were identified by at least three of the aforementioned bioinformatic tools. Subsequently, subcellular localization analysis was examined and the gene ontology analysis revealed diverse biological processes, cellular components, and molecular functions. Remarkably, E1WPR3 was identified as a virulent and essential gene among the HPs. This study presents a comprehensive exploration of B. fragilis HPs, shedding light on their potential roles and contributing to a deeper understanding of this organism's functional landscape.

Screening Balanites aegyptiaca for inhibitors against putative drug targets in Microsporum gypseum - Subtractive proteome, docking and simulation approach.

Microsporum gypseum is a keratinophilic fungi grouped under dermatophytes infecting skin, hair and nail portions in human and animals causing tinea corporis, tinea facei and tinea capitis. As both human and fungi are eukaryotes, the available drugs for treating dermatophytes produce some side effects due to drug interaction with human also. Apart from this, the gut microbiota has a very big role in the health of human which should not be affected by the drugs. Hence this study focused on finding a target which is unique and essential to M. gypseum and non-homologous to human and gut microbiota, non-homologous to human domain architecture, highly interacting with other proteins, sub-cellular localization of proteins and non-druggability analysis of the targets using subtractive proteomics approach which resulted with 3 novel drug targets from M. gypseum which were modeled using I-TASSER, refined by ModRefiner and validated by PROCHECK. Further these targets were docked with compounds identified through LC-MS of fractioned methanol extract of B. aegyptiaca fruit pulp using Glide module and the stability of the docked complex was analyzed by molecular dynamics simulation using Desmond module of Schrodinger. Cyanidin-3-O-rhamnoside had better interaction with all the targets and Taurocholic acid had better result with ECCP which suggests the multi-targeting potency of these two compounds against M. gypseum which has to be confirmed by in vitro and in vivo studies.

Putative Drug Target Identification in Tinea Causing Pathogen Trichophyton rubrum Using Subtractive Proteomics Approach.

Trichophyton, important among the three keratinophylic fungi grouped as dermatophytes, is known to cause superficial infections in skin, nail and hair of all the living organisms. The side effects produced by the drugs currently administered to counter these infections have necessitated the search for novel targets. The present study focused on finding putative drug targets in Trichophyton rubrum using the subtractive proteomics approach where its whole proteome was analyzed to find proteins non-homologous to humans inclusive of their gut flora and human protein domain but essential to T. rubrum, to identify sub-cellular localization, functional classification of uncharacterized proteins and to analyze the protein network, druggability and pathway of the targets. The study's strength relies on its addition of important steps namely, non-homology of the pathogen domain to human domain, non-homology to gut microbiota and substantiation of the importance of the targets in networking by node deletion to the existing methods in drug discovery for dermatophytoses. The study has resulted in the identification of two novel drug targets from the whole proteome of T. rubrum that are not present in human and human gut microbiota.