title: Transcriptomic analysis displays the effect of (-)-roemerine on the motility and nutrient uptake in Escherichia coli.
abstract: Among 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 μg/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.
authors.affiliation: Department of Bioengineering, Faculty of Engineering, Marmara University, Building D, Office:321, 34722, Kadikoy, Istanbul, Turkey.
authors.forename: Dilara
authors.initials: D
authors.lastname: Ayyildiz
authors.affiliation: Department of Bioengineering, Faculty of Engineering, Marmara University, Building D, Office:321, 34722, Kadikoy, Istanbul, Turkey.
authors.forename: Kazim Yalcin
authors.initials: KY
authors.lastname: Arga
authors.affiliation: Department of Bioengineering, Faculty of Engineering, Marmara University, Building D, Office:321, 34722, Kadikoy, Istanbul, Turkey.
authors.forename: Fatma Gizem
authors.initials: FG
authors.lastname: Avci
authors.affiliation: Department of Bioengineering, Faculty of Engineering, Marmara University, Building D, Office:321, 34722, Kadikoy, Istanbul, Turkey.
authors.forename: Fatma Ece
authors.initials: FE
authors.lastname: Altinisik
authors.affiliation: Department of Pharmacognosy, Faculty of Pharmacy, Istanbul University, Istanbul, Turkey.
authors.forename: Caglayan
authors.initials: C
authors.lastname: Gurer
authors.affiliation: Department of Pharmacognosy, Faculty of Pharmacy, Istanbul University, Istanbul, Turkey.
authors.forename: Gizem
authors.initials: G
authors.lastname: Gulsoy Toplan
authors.affiliation: Department of Bioengineering, Faculty of Engineering, Marmara University, Building D, Office:321, 34722, Kadikoy, Istanbul, Turkey.
authors.forename: Dilek
authors.initials: D
authors.lastname: Kazan
authors.affiliation: Heidelberg University Biochemistry Center, University Heidelberg, Heidelberg, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Wozny
authors.affiliation: Heidelberg University Biochemistry Center, University Heidelberg, Heidelberg, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Brügger
authors.affiliation: Department of Bioengineering, Faculty of Engineering, Marmara University, Building D, Office:321, 34722, Kadikoy, Istanbul, Turkey.
authors.forename: Bulent
authors.initials: B
authors.lastname: Mertoglu
authors.affiliation: Department of Bioengineering, Faculty of Engineering, Marmara University, Building D, Office:321, 34722, Kadikoy, Istanbul, Turkey. berna.akbulut@marmara.edu.tr.
authors.forename: Berna
authors.initials: B
authors.lastname: Sariyar Akbulut
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D001692:Biological Transport / Q000187:drug effects / Q000235:genetics; D002465:Cell Movement / Q000187:drug effects*; D004734:Energy Metabolism / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000235:genetics / Q000382:microbiology; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D006801:Humans
chemical_list: D000470:Alkaloids; D000900:Anti-Bacterial Agents; C030169:roemerine
keywords: Antibacterial; Antimicrobial resistance; Drug; Escherichia coli; Roemerine; Transcriptome