Design, synthesis and exploration of novel triazinoindoles as potent quorum-sensing inhibitors and radical quenchers.

Background: Antimicrobial resistance has become a critical health concern, and quorum-sensing exacerbates the resistance by facilitating cell-to-cell communication within the microbial community, leading to severe pathogenic outbreaks. Methods & results: Novel 1-(2-((5H-[1,2,4]-triazino[5,6-b]indol-3-yl)thio)acetyl)indoline-2,3-diones were synthesized. The title compounds exhibit outstanding anti-quorum-sensing efficacy, and compound 7g demonstrated the maximum proficiency (IC50 = 0.0504 µg/ml). The hybrids displayed potent antioxidant action, and compound 7c showed the highest antioxidant ability (IC50 = 40.71 µg/ml). Molecular docking of the isatin hybrids against DNA gyrase and quorum-sensing receptor CviR validated the observed in vitro findings. The befitting pharmacokinetic profile of the synthesized drug candidates was ascertained through absorption, distribution, metabolism, excretion and toxicity screening. Conclusion: The remarkable biocompetence of the synthesized triazinoindoles may help to combat drug-resistant infections.

Western Indian Rural Gut Microbial Diversity in Extreme Prakriti Endo-Phenotypes Reveals Signature Microbes.

Heterogeneity amidst healthy individuals at genomic level is being widely acknowledged. This, in turn, is modulated by differential response to environmental cues and treatment regimens, necessitating the need for stratified/personalized therapy. We intend to understand the molecular determinants of Ayurvedic way (ancient Indian system of medicine) of endo-phenotyping individuals into distinct constitution types termed "Prakriti," which forms the basis of personalized treatment. In this study, we explored and analyzed the healthy human gut microbiome structure within three predominant Prakriti groups from a genetically homogenous cohort to discover differentially abundant taxa, using 16S rRNA gene based microbial community profiling. We found Bacteroidetes and Firmicutes as major gut microbial components in varying composition, albeit with similar trend across Prakriti. Multiple species of the core microbiome showed differential abundance within Prakriti types, with gender specific signature taxons. Our study reveals that despite overall uniform composition of gut microbial community, healthy individuals belonging to different Prakriti groups have enrichment of specific bacteria. It highlights the importance of Prakriti based endo-phenotypes to explain the variability amongst healthy individuals in gut microbial flora that have important consequences for an individual's health, disease and treatment.

Metagenomic Profiling of Soil Microbes to Mine Salt Stress Tolerance Genes.

Osmotolerance is one of the critical factors for successful survival and colonization of microbes in saline environments. Nonetheless, information about these osmotolerance mechanisms is still inadequate. Exploration of the saline soil microbiome for its community structure and novel genetic elements is likely to provide information on the mechanisms involved in osmoadaptation. The present study explores the saline soil microbiome for its native structure and novel genetic elements involved in osmoadaptation. 16S rRNA gene sequence analysis has indicated the dominance of halophilic/halotolerant phylotypes affiliated to Proteobacteria, Actinobacteria, Gemmatimonadetes, Bacteroidetes, Firmicutes, and Acidobacteria. A functional metagenomics approach led to the identification of osmotolerant clones SSR1, SSR4, SSR6, SSR2 harboring BCAA_ABCtp, GSDH, STK_Pknb, and duf3445 genes. Furthermore, transposon mutagenesis, genetic, physiological and functional studies in close association has confirmed the role of these genes in osmotolerance. Enhancement in host osmotolerance possibly though the cytosolic accumulation of amino acids, reducing equivalents and osmolytes involving BCAA-ABCtp, GSDH, and STKc_PknB. Decoding of the genetic elements prevalent within these microbes can be exploited either as such for ameliorating soils or their genetically modified forms can assist crops to resist and survive in saline environment.