New antibiotics are urgently needed to address the mounting resistance challenge. In early drug discovery one of the bottlenecks is the elucidation of targets and mechanisms. To accelerate antibiotic research, we provide a proteomic approach for the rapid classification of compounds into those with precedented and unprecedented modes of action. We established a proteomic response library of Bacillus subtilis covering 91 antibiotics and comparator compounds, and a mathematical approach was developed to aid data analysis. The Comparison of Proteomic Responses (CoPR) allows the rapid identification of antibiotics with dual mechanisms of action as shown for atypical tetracyclines. It also aids in generating hypotheses on mechanisms of action as presented for salvarsan (arsphenamine) and the antirheumatic agent auranofin, which is under consideration for repurposing. Proteomic profiling also provides insights into the impact of antibiotics on bacterial physiology through analysis of marker proteins indicative of the impairment of cellular processes and structures. As demonstrated for trans-translation, a promising target not yet exploited clinically, proteomic profiling supports chemical biology approaches to investigating bacterial physiology.
Biotransformation of host bile salts by gut microbes results in generation of secondary bile salt species that have biological and physicochemical properties that are distinct from the parent compounds. There is increased awareness that a bile salt–gut microbiome axis modulates various processes in the host, including innate and adaptive immunity, by interaction of microbial bile salt metabolites with host receptors. Omics and targeted approaches have vastly expanded the number and repertoire of secondary bile salt species. A new class of microbial bile salt metabolites was reported in 2020 and comprises bile salts that are conjugated by microbial enzymes. Amino acids other than those employed by host enzymes (glycine and taurine) are used as substrates in the formation of these microbial bile salt conjugates (MBSCs). Leucocholic acid, phenylalanocholic acid and tyrosocholic acid were the first MBSCs identified in mice and humans. The number of distinct MBSCs is now approaching 50, with variation both at the level of bile salt and amino acid employed for conjugation. Evidence is emerging that MBSC generation is a common feature of human gut bacteria, and initial links with disease states have been reported. In this review, we discuss this intriguing new class of secondary bile salts, with yet enigmatic function.
Ö Z E TKlasik Türk Edebiyatı araştırmalarında manzum metinlerin, bunlar arasında da divanların önemli bir yeri vardır. Yurdumuzda ve dünyanın değişik kütüphanelerinde bulunan bu eserler üzerinde yapılan metin ve inceleme çalışmalarının kültür ve medeniyetimizin inşasındaki yeri tartışılmazdır. Bu sebeple özellikle yurt dışı kütüphanelerinde bulunan el yazması nüshaların tanıtılması, Klasik Türk Edebiyatı sahasının önemli çalışma alanlarından biridir. Bu çalışmada İran Kütüphanelerinde bulunan ve DENA katalogunda yer alan Türkçe, Türkçe-Farsça, Türkçe-Farsça-Arapça el yazması divanlara ait bilgiler tercüme edilerek araştırmacıların istifadesine sunulmuştur.
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