Person: SARIYAR AKBULUT, BERNA
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SARIYAR AKBULUT
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Publication Metadata only Transcriptomic analysis displays the effect of (-)-roemerine on the motility and nutrient uptake in Escherichia coli(SPRINGER, 2017) SARIYAR AKBULUT, BERNA; Ayyildiz, Dilara; Arga, Kazim Yalcin; Avci, Fatma Gizem; Altinisik, Fatma Ece; Gurer, Caglayan; Toplan, Gizem Gulsoy; Kazan, Dilek; Wozny, Katharina; Bruegger, Britta; Mertoglu, Bulent; Akbulut, Berna SariyarAmong the different families of plant alkaloids, (-)-roemerine, an aporphine type, was recently shown to possess significant antibacterial activity in Escherichia coli. Based on the increasing demand for antibacterials with novel mechanisms of action, the present work investigates the potential of the plant-derived alkaloid (-)-roemerine as an antibacterial in E. coli cells using microarray technology. Analysis of the genome-wide transcriptional reprogramming in cells after 60 min treatment with 100 mu g/mL (-)-roemerine showed significant changes in the expression of 241 genes (p value < 0.05 and fold change > 2). Expression of selected genes was confirmed by qPCR. Differentially expressed genes were classified into functional categories to map biological processes and molecular pathways involved. Cellular activities with roles in carbohydrate transport and metabolism, energy production and conversion, lipid transport and metabolism, amino acid transport and metabolism, two-component signaling systems, and cell motility (in particular, the flagellar organization and motility) were among metabolic processes altered in the presence of (-)-roemerine. The down-regulation of the outer membrane proteins probably led to a decrease in carbohydrate uptake rate, which in turn results in nutrient limitation. Consequently, energy metabolism is slowed down. Interestingly, the majority of the expressional alterations were found in the flagellar system. This suggested reduction in motility and loss in the ability to form biofilms, thus affecting protection of E. coli against host cell defense mechanisms. In summary, our findings suggest that the antimicrobial action of (-)-roemerine in E. coli is linked to disturbances in motility and nutrient uptake.Publication Metadata only What Are the Multi-Omics Mechanisms for Adaptation by Microorganisms to High Alkalinity? A Transcriptomic and Proteomic Study of a Bacillus Strain with Industrial Potential(MARY ANN LIEBERT, INC, 2018) SAYAR, AHMET ALP; Kaya, Fatma Ece Altinisik; Avci, Fatma Gizem; Sayar, Nihat Alpagu; Kazan, Dilek; Sayar, Ahmet Alp; Akbulut, Berna SariyarAlkaliphilic organisms are among an industrially important class of extremophile microorganisms with the ability to thrive at pH 10-11.5. Microorganisms that exhibit alkaliphilic characteristics are sources of alkali-tolerant enzymes such as proteases, starch degrading enzymes, cellulases, and metabolites such as antibiotics, enzyme inhibitors, siderophores, organic acids, and cholic acid derivatives, which have found various applications in industry for human and environmental health. Yet, multi-omics mechanisms governing adaptation to high alkalinity have been poorly studied. We undertook the present work to understand, as a case study, the alkaliphilic adaptation strategy of the novel microorganism, Bacillus marmarensis DSM 21297, to alkaline conditions using a multi-omics approach that employed transcriptomics and proteomics. As alkalinity increased, bacteria remodeled the peptidoglycan layer by changing peptide moieties along with the peptidoglycan constituents and altered the cell membrane to reduce lipid motility and proton leakiness to adjust intracellular pH. Different transporters also contributed to the maintenance of this pH homeostasis. However, unlike in most well-known alkaliphiles, not only sodium ions but also potassium ions were involved in this process. Interestingly, increased pH has triggered the expression of neither general stress proteins nor gene encoding proteins associated with heat, salt, and nutrient stresses. Only an increase in the expression of oxidative stress related genes was evident. Endospore formation, also a phenomenon closely linked to stress, was unclear. This questioned if high pH was a real stress for B. marmarensis. These new findings, corroborated using the multi-omics approach of the present case study, broaden the knowledge on the mechanisms of alkaliphilic adaptation and might also potentially offer useful departure points for further industrial applications with other microorganisms.Publication Metadata only Targeting a hidden site on class A beta-lactamases(ELSEVIER SCIENCE INC, 2018) SARIYAR AKBULUT, BERNA; Avci, Fatma Gizem; Altinisik, Fatma Ece; Karacan, Ipek; Karagoz, Duygu Senturk; Ersahin, Serhat; Eren, Ayse; Sayar, Nihat Alpagu; Ulu, Didem Vardar; Ozkirimli, Elif; Akbulut, Berna SariyarIncreasing resistance against available orthosteric beta-lactamase inhibitors necessitates the search for novel and powerful inhibitor molecules. In this respect, allosteric inhibitors serve as attractive alternatives. Here, we examine the structural basis of inhibition in a hidden, druggable pocket in TEM-1 betalactamase. Based on crystallographic evidence that 6-cyclohexyl-1-hexyl-beta-D-maltoside (CYMAL-6) binds to this site, first we determined the kinetic mechanism of inhibition by CYMAL-6. Activity measurements with CYMAL-6 showed that it competitively inhibits the wild type enzyme. Interestingly, it exhibits a steep dose -response curve with an IC50 of 100 mu M. The IC50 value changes neither with different enzyme concentration nor with incubation of the enzyme with the inhibitor, showing that inhibition is not aggregation -based. The presence of the same concentrations of CYMAL-6 does not influence the activity of lactate dehydrogenase, further confirming the specificity of CYMAL-6 for TEM-1 beta-lactamase. Then, we identified compounds with high affinity to this allosteric site by virtual screening using Glide and Schrodinger Suite. Virtual screening performed with 500,000 drug like compounds from the ZINC database showed that top scoring compounds interact with the hydrophobic pocket that forms between H10 and Hll helices and with the catalytically important Arg244 residue through pi -cation interactions. Discovery of novel chemical scaffolds that target this allosteric site will pave the way for a new avenue in the design of new antimicrobials. (C) 2018 Elsevier Inc. All rights reserved.