Publikationen im Open Access gefördert durch die UB
Dauerhafte URI für die Sammlung
Suchen
Auflistung Publikationen im Open Access gefördert durch die UB nach Autor:in "Abu Mraheil, Mobarak"
Gerade angezeigt 1 - 5 von 5
Treffer pro Seite
Sortieroptionen
Item A Single Residue within the MCR-1 Protein Confers Anticipatory Resilience(2023) Frantz, Renate; Gwozdzinski, Konrad; Gisch, Nicolas; Doijad, Swapnil Prakash; Hudel, Martina; Wille, Maria; Abu Mraheil, Mobarak; Schwudke, Dominik; Imirzalioglu, Can; Falgenhauer, Linda; Ehrmann, Michael; Chakraborty, TrinadThe envelope stress response (ESR) of Gram-negative enteric bacteria senses fluctuations in nutrient availability and environmental changes to avert damage and promote survival. It has a protective role toward antimicrobials, but direct interactions between ESR components and antibiotic resistance genes have not been demonstrated. Here, we report interactions between a central regulator of ESR viz., the twocomponent signal transduction system CpxRA (conjugative pilus expression), and the recently described mobile colistin resistance protein (MCR-1). Purified MCR-1 is specifically cleaved within its highly conserved periplasmic bridge element, which links its Nterminal transmembrane domain with the C-terminal active-site periplasmic domain, by the CpxRA-regulated serine endoprotease DegP. Recombinant strains harboring cleavage site mutations in MCR-1 are either protease resistant or degradation susceptible, with widely differing consequences for colistin resistance. Transfer of the gene encoding a degradation-susceptible mutant to strains that lack either DegP or its regulator CpxRA restores expression and colistin resistance. MCR-1 production in Escherichia coli imposes growth restriction in strains lacking either DegP or CpxRA, effects that are reversed by transactive expression of DegP. Excipient allosteric activation of the DegP protease specifically inhibits growth of isolates carrying mcr-1 plasmids. As CpxRA directly senses acidification, growth of strains at moderately low pH dramatically increases both MCR-1-dependent phosphoethanolamine (PEA) modification of lipid A and colistin resistance levels. Strains expressing MCR-1 are also more resistant to antimicrobial peptides and bile acids. Thus, a single residue external to its active site induces ESR activity to confer resilience in MCR-1-expressing strains to commonly encountered environmental stimuli, such as changes in acidity and antimicrobial peptides. Targeted activation of the nonessential protease DegP can lead to the elimination of transferable colistin resistance in Gram-negative bacteria.Item Bioactive Azadirachta indica and Melia azedarach leaves extracts with anti-SARS-CoV-2 and antibacterial activities(2023) Hemdan, Bahaa A.; Mostafa, Ahmed; Elbatanony, Marwa M.; El-Feky, Amal M.; Paunova-Krasteva, Tsvetelina; Stoitsova, Stoyanka; El-Liethy, Mohamed Azab; El-Taweel, Gamila E.; Abu Mraheil, MobarakThe leaves of Azadirachta indica L. and Melia azedarach L., belonging to Meliaceae family, have been shown to have medicinal benefits and are extensively employed in traditional folk medicine. Herein, HPLC analysis of the ethyl acetate fraction of the total methanolic extract emphasized the enrichment of both A. indica L., and M. azedarach L. leaves extracts with phenolic and flavonoids composites, respectively. Besides, 4 limonoids and 2 flavonoids were isolated using column chromatography. By assessing the in vitro antiviral activities of both total leaves extracts against Severe Acute Respiratory Syndrome Corona virus 2 (SARS-CoV-2), it was found that A. indica L. and M. azedarach L. have robust anti-SARSCoV- 2 activities at low half-maximal inhibitory concentrations (IC50) of 8.451 and 6.922 μg/ mL, respectively. Due to the high safety of A. indica L. and M. azedarach L. extracts with half-maximal cytotoxic concentrations (CC50) of 446.2 and 351.4 μg/ml, respectively, both displayed extraordinary selectivity indices (SI>50). A. indica L. and M. azedarach L. leaves extracts could induce antibacterial activities against both Gram-negative and positive bacterial strains. The minimal inhibitory concentrations of A. indica L. and M. azedarach L. leaves extracts varied from 25 to 100 mg/mL within 30 min contact time towards the tested bacteria. Our findings confirm the broad-spectrum medicinal value of A. indica L. and M. azedarach L. leaves extracts. Finally, additional in vivo investigations are highly recommended to confirm the anti-COVID-19 and antimicrobial activities of both plant extracts.Item Reassessment of the Listeria monocytogenes pan-genome reveals dynamic integration hotspots and mobile genetic elements as major components of the accessory genome(2013) Kuenne, Carsten; Billion, André; Abu Mraheil, Mobarak; Strittmatter, Axel; Daniel, Rolf; Goesmann, Alexander; Barbuddheand , Sukhadeo; Hain, Torsten; Chakraborty, TrinadBackground: Listeria monocytogenes is an important food-borne pathogen and model organism for host-pathogeninteraction, thus representing an invaluable target considering research on the forces governing the evolution ofsuch microbes. The diversity of this species has not been exhaustively explored yet, as previous efforts have focusedon analyses of serotypes primarily implicated in human listeriosis. We conducted complete genome sequencing of11 strains employing 454 GS FLX technology, thereby achieving full coverage of all serotypes including the firstcomplete strains of serotypes 1/2b, 3c, 3b, 4c, 4d, and 4e. These were comparatively analyzed in conjunction withpublicly available data and assessed for pathogenicity in the Galleria mellonella insect model.Results: The species pan-genome of L. monocytogenes is highly stable but open, suggesting an ability to adapt tonew niches by generating or including new genetic information. The majority of gene-scale differences representedby the accessory genome resulted from nine hyper variable hotspots, a similar number of different prophages,three transposons (Tn916, Tn554, IS3-like), and two mobilizable islands. Only a subset of strains showed CRISPR/Casbacteriophage resistance systems of different subtypes, suggesting a supplementary function in maintenance ofchromosomal stability. Multiple phylogenetic branches of the genus Listeria imply long common histories of strainsof each lineage as revealed by a SNP-based core genome tree highlighting the impact of small mutations for theevolution of species L. monocytogenes. Frequent loss or truncation of genes described to be vital for virulence orpathogenicity was confirmed as a recurring pattern, especially for strains belonging to lineages III and II. Newcandidate genes implicated in virulence function were predicted based on functional domains and phylogeneticdistribution. A comparative analysis of small regulatory RNA candidates supports observations of a differentialdistribution of trans-encoded RNA, hinting at a diverse range of adaptations and regulatory impact.Conclusions: This study determined commonly occurring hyper variable hotspots and mobile elements as primaryeffectors of quantitative gene-scale evolution of species L. monocytogenes, while gene decay and SNPs seem torepresent major factors influencing long-term evolution. The discovery of common and disparately distributedgenes considering lineages, serogroups, serotypes and strains of species L. monocytogenes will assist in diagnostic,phylogenetic and functional research, supported by the comparative genomic GECO-LisDB analysis server(http://bioinfo.mikrobio.med.uni-giessen.de/geco2lisdb).Item SecA2 Associates with Translating Ribosomes and Contributes to the Secretion of Potent IFN-ß Inducing RNAs(2022) Teubner, Lisa; Frantz, Renate; La Pietra, Luigi; Hudel, Martina; Bazant, Jasmin; Lochnit, Günter; Eismann, Lena; Kramer, Günter; Chakraborty, Trinad; Abu Mraheil, MobarakItem Toward Homogenous Antibody Drug Conjugates Using Enzyme-Based Conjugation Approaches(2021) Hussain, Ahmad; Grimm, Armin; Sheng, Wenjie; Zhang, Chaoyu; Al-Rawe, Marwah; Bräutigam, Karen; Abu Mraheil, Mobarak; Zeppernick, Felix; Meinhold-Heerlein, Ivo