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852 results on '"Velkov, Tony"'

152. Comparative Metabolomics Reveals Key Pathways Associated With the Synergistic Killing of Colistin and Sulbactam Combination Against Multidrug-Resistant Acinetobacter baumannii

Author

Han, Mei-Ling, primary, Liu, Xiaofen, additional, Velkov, Tony, additional, Lin, Yu-Wei, additional, Zhu, Yan, additional, Creek, Darren J., additional, Barlow, Christopher K., additional, Yu, Heidi H., additional, Zhou, Zhihui, additional, Zhang, Jing, additional, and Li, Jian, additional

Published
2019
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153. Effects of the antibiotic component on in-vitro bacterial killing, physico-chemical properties, aerosolization and dissolution of a ternary-combinational inhalation powder formulation of antibiotics for pan-drug resistant Gram-negative lung infections

Author

Mangal, Sharad, primary, Huang, Jiayang, additional, Shetty, Nivedita, additional, Park, Heejun, additional, Lin, Yu-wei, additional, Yu, Heidi H., additional, Zemlyanov, Dmitry, additional, Velkov, Tony, additional, Li, Jian, additional, and Zhou, Qi (Tony), additional

Published
2019
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154. Novel Polymyxin Combination with the Antiretroviral Zidovudine Exerts Synergistic Killing against NDM-Producing Multidrug-Resistant Klebsiella pneumoniae

Author

Lin, Yu-Wei, primary, Abdul Rahim, Nusaibah, additional, Zhao, Jinxin, additional, Han, Mei-Ling, additional, Yu, Heidi H., additional, Wickremasinghe, Hasini, additional, Chen, Ke, additional, Wang, Jiping, additional, Paterson, David L., additional, Zhu, Yan, additional, Rao, Gauri G., additional, Zhou, Qi Tony, additional, Forrest, Alan, additional, Velkov, Tony, additional, and Li, Jian, additional

Published
2019
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158. An optimised Cu(0)-RDRP approach for the synthesis of lipidated oligomeric vinyl azlactone: toward a versatile antimicrobial materials screening platform

Author

Grace, James L., primary, Amado, Maite, additional, Reid, Janet C., additional, Elliott, Alysha G., additional, Landersdorfer, Cornelia B., additional, Truong, Nghia P., additional, Kempe, Kristian, additional, Cooper, Matthew A., additional, Davis, Thomas P., additional, Montembault, Véronique, additional, Pascual, Sagrario, additional, Fontaine, Laurent, additional, Velkov, Tony, additional, Quinn, John F., additional, and Whittaker, Michael R., additional

Published
2019
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159. Comparative analysis of phosphoethanolamine transferases involved in polymyxin resistance across ten clinically relevant Gram-negative bacteria

Author

Huang, Jiayuan, Zhu, Yan, Han, Meiling, Li, Mengyao, Song, Jiangning, Velkov, Tony, Li, Chen, and Li, Jian

Subjects
Base Sequence, Escherichia coli Proteins, food and beverages, Membrane Proteins, Ethanolaminephosphotransferase, Article, Anti-Bacterial Agents, Phosphotransferases (Alcohol Group Acceptor), Lipid A, Ethanolamines, Catalytic Domain, Drug Resistance, Multiple, Bacterial, Gram-Negative Bacteria, Amino Acid Sequence, Polymyxins, Gram-Negative Bacterial Infections, Sequence Alignment, Phylogeny
Abstract

The rapid emergence of Gram-negative 'superbugs' has become a significant threat to human health globally, and polymyxins have become a last-line therapy for these very problematic pathogens. Polymyxins exhibit their antibacterial killing by initial interaction with lipid A in Gram-negative bacteria. Polymyxin resistance can be mediated by phosphoethanolamine (PEA) modification of lipid A, which abolishes the initial electrostatic interaction with polymyxins. Both chromosome-encoded (e.g. EptA, EptB and EptC) and plasmid-encoded (e.g. MCR-1 and MCR-2) PEA transferases have been reported in Gram-negative bacteria; however, their sequence and functional heterogeneity remain unclear. This article reports a comparative analysis of PEA transferases across 10 clinically relevant Gram-negative bacterial species using multiple sequence alignment and phylogenetic analysis. The results show that the pairwise identities among chromosome-mediated EptA, EptB and EptC from Escherichia coli are low, and EptA shows the greatest similarity with MCR-1 and MCR-2. Among PEA transferases from representative strains of 10 clinically relevant species, the catalytic domain is more conserved compared with the transmembrane domain. In particular, PEA acceptor sites and zinc-binding pockets show high conservation between different species, indicating their potential importance for the function of PEA transferases. The evolutionary relationship of MCR-1, MCR-2 and EptA from the 10 selected bacterial species was evaluated by phylogenetic analysis. Cluster analysis illustrates that 325 EptA from 275 strains of 10 species within each individual species are highly conserved, whereas interspecies conservation is low. This comparative analysis provides key bioinformatic information to better understand the mechanism of polymyxin resistance via PEA modification of lipid A.

Published
2017

161. Graphene-enhanced 3D chemical mapping of biological specimens at near-atomic resolution

Author

Adineh, Vahid R., Zheng, Changxi, Zhang, Qianhui, Marceau, Ross K. W., Liu, Boyin, Chen, Yu, Si, Kae J., Weyland, Matthew, Velkov, Tony, Cheng, Wenlong, Li, Jian, Fu, Jing, Adineh, Vahid R., Zheng, Changxi, Zhang, Qianhui, Marceau, Ross K. W., Liu, Boyin, Chen, Yu, Si, Kae J., Weyland, Matthew, Velkov, Tony, Cheng, Wenlong, Li, Jian, and Fu, Jing

Published
2018

162. Investigating the interaction of octapeptin A3 with model bacterial membranes

Author

Han, Mei-Ling, Shen, Hsin-Hui, Hansford, Karl A., Schneider, Elena. K., Sivanesan, Sivashangarie, Kade, Roberts, D., Thompson, Philip E., Le Brun, Anton P., Zhu, Yan, Sani, Marc-Antoine, Separovic, Frances, Blaskovich, Mark A.T., Baker, Mark A., Moskowitz, Samuel M., Cooper, Matthew A., Li, Jian, and Velkov, Tony

Subjects
0301 basic medicine, 1,2-Dipalmitoylphosphatidylcholine, medicine.drug_class, Polymyxin, 030106 microbiology, Lipid Bilayers, Phospholipid, Biology, Article, Cell membrane, Lipid A, 03 medical and health sciences, chemistry.chemical_compound, Lipopeptides, Drug Resistance, Multiple, Bacterial, medicine, Carbohydrate Conformation, Lipid bilayer, Unilamellar Liposomes, Polymyxin B, Cell Membrane, 030104 developmental biology, Infectious Diseases, medicine.anatomical_structure, Membrane, chemistry, Biochemistry, Pseudomonas aeruginosa, lipids (amino acids, peptides, and proteins), Neutron reflectometry, Bacterial outer membrane, Protein Binding
Abstract

Octapeptins are cyclic lipopeptides that do not exhibit cross-resistance with polymyxins and have a broader spectrum of activity that includes fungi and Gram-positive bacteria. In the present study we investigated the interaction of octapeptin A3 with asymmetric outer membrane models of the Gram-negative pathogen Pseudomonas aeruginosa, using neutron reflectometry, together with fluorimetric and calorimetry methods. For the first time our neutron reflectometry results reveal that the interaction of octapeptin A3 with the Gram-negative outer membrane involves an initial transient polar interaction with the phospholipid and lipid A head groups, followed by the penetration of the entire octapeptin molecule into the fatty acyl core of the outer membrane. This mechanism contrasts that of polymyxin B which specifically targets lipid A, whereas octapeptins appear to target both lipid A and phospholipids. Furthermore, the mechanism of octapeptins does not appear to be highly dependent on an initial complimentary electrostatic interaction with lipid A, which accounts for their ability to bind to the lipid A of polymyxin-resistant Gram-negative bacteria which is modified with cationic moieties that act to electrostatically repel the cationic polymyxin molecule. The presented findings shed new light on the mechanism whereby octapeptins penetrate the outer membrane of polymyxin-resistant Gram-negative pathogens and highlight their potential as candidates for development as new antibiotics against problematic multi-drug resistant pathogens.

Published
2017

163. Hydrolyzable Poly(PEGA) Colistin Prodrugs through Copper-mediated Photo-induced Living Radical Polymerization

Author

Zhu, Chongyu, Schneider, Elena K., Nikolaou, Vasiliki, Klein, Tobias, Li, Jian, Davis, Thomas P., Whittaker, Michael R., Wilson, Paul, Kempe, Kristian, Velkov, Tony, and Haddleton, David M.

Subjects
Colistin, Hydrolysis, Photochemical Processes, Article, Drug Resistance, Multiple, Anti-Bacterial Agents, Polyethylene Glycols, Polymerization, Structure-Activity Relationship, Acrylates, Gram-Negative Bacteria, lipids (amino acids, peptides, and proteins), Prodrugs, Copper
Abstract

Through the recently developed copper-mediated photo-induced living radical polymerization (CP-LRP), a novel and well-defined polymeric prodrug of the antimicrobial lipopeptide colistin has been developed. A colistin initiator (Boc5-col-Br2) was synthesized through the modification of colistin on both of its threonine residues using a cleavable initiator linker, 2-(2-bromo-2-methylpropanoyloxy) acetic acid (BMPAA) and used for the polymerization of acrylates via CP-LRP. Polymerization proceeds from both sites of the colistin initiator, and through the polymerization of PEGA480, three water-soluble polymer-colistin conjugates (col-PPEGA, DP = 5, 10, 20) were achieved with high yield (conv. ≥ 93%) and narrow dispersities (Đ < 1.3) in 2 – 4 hours. Little or no effect on the structure/activity of the colistin was observed during the synthesis and most of the active colistin can be recovered from the conjugates in vitro within 2 days. Furthermore, in vitro biological analyses including disk diffusion, broth microdilution and time-kill studies suggested all the conjugates have the ability to inhibit the growth of multi-drug resistant (MDR) Gram-negative bacteria, of which col-PPEGA DP5 and DP10 showed similar or better antibacterial performance compared to the clinically relevant colistin prodrug CMS, indicating their potential as an alternative antimicrobial therapy. Moreover, considering the control over the polymerization, CP-LRP technique has the potential to provide an alternative platform for the development of polymer bioconjugates.

Published
2017

165. Synthesis and structure−activity relationships of teixobactin.

Author

Karas, John A., Chen, Fan, Schneider‐Futschik, Elena K., Kang, Zhisen, Hussein, Maytham, Swarbrick, James, Hoyer, Daniel, Giltrap, Andrew M., Payne, Richard J., Li, Jian, and Velkov, Tony

Subjects
STRUCTURE-activity relationships, METHICILLIN-resistant staphylococcus aureus, SOIL microbiology, BIOCHEMICAL mechanism of action, BACTERIAL diseases, COLISTIN
Abstract

The discovery of antibiotics has led to the effective treatment of bacterial infections that were otherwise fatal and has had a transformative effect on modern medicine. Teixobactin is an unusual depsipeptide natural product that was recently discovered from a previously unculturable soil bacterium and found to possess potent antibacterial activity against several Gram positive pathogens, including methicillin‐resistant Staphylococcus aureus and vancomycin‐resistant Enterococci. One of the key features of teixobactin as an antibiotic lead is that resistance could not be generated in a laboratory setting. This is proposed to be a result of a mechanism of action that involves binding to essential cell wall synthesis building blocks, lipid II and lipid III. Since the initial isolation report in 2015, significant efforts have been made to understand its unique mechanism of action, develop efficient synthetic routes for its production, and thus enable the generation of analogues for structure−activity relationship studies and optimization of its pharmacological properties. Our review provides a comprehensive treatise on the progress in understanding teixobactin chemistry, structure−activity relationships, and mechanisms of antibacterial activity. Teixobactin represents an exciting starting point for the development of new antibiotics that can be used to combat multidrug‐resistant bacterial ("superbug") infections. [ABSTRACT FROM AUTHOR]

Published
2020
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176. Polymyxin B in Combination with Enrofloxacin Exerts Synergistic Killing against Extensively Drug-Resistant Pseudomonas aeruginosa

Author

Lin, Yu-Wei, primary, Yu, Heidi H., additional, Zhao, Jinxin, additional, Han, Mei-Ling, additional, Zhu, Yan, additional, Akter, Jesmin, additional, Wickremasinghe, Hasini, additional, Walpola, Hasini, additional, Wirth, Veronika, additional, Rao, Gauri G., additional, Forrest, Alan, additional, Velkov, Tony, additional, and Li, Jian, additional

Published
2018
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182. Genome-scale metabolic modeling of responses to polymyxins inPseudomonas aeruginosa

Author

Zhu, Yan, primary, Czauderna, Tobias, additional, Zhao, Jinxin, additional, Klapperstueck, Matthias, additional, Maifiah, Mohd Hafidz Mahamad, additional, Han, Mei-Ling, additional, Lu, Jing, additional, Sommer, Björn, additional, Velkov, Tony, additional, Lithgow, Trevor, additional, Song, Jiangning, additional, Schreiber, Falk, additional, and Li, Jian, additional

Published
2018
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186. Mechanistic Insights From Global Metabolomics Studies into Synergistic Bactericidal Effect of a Polymyxin B Combination With Tamoxifen Against Cystic Fibrosis MDR Pseudomonas aeruginosa

Author

Hussein, Maytham, primary, Han, Mei-Ling, additional, Zhu, Yan, additional, Schneider-Futschik, Elena K., additional, Hu, Xiaohan, additional, Zhou, Qi Tony, additional, Lin, Yu-Wei, additional, Anderson, Dovile, additional, Creek, Darren J., additional, Hoyer, Daniel, additional, Li, Jian, additional, and Velkov, Tony, additional

Published
2018
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187. Rapamycin Confers Neuroprotection against Colistin-Induced Oxidative Stress, Mitochondria Dysfunction, and Apoptosis through the Activation of Autophagy and mTOR/Akt/CREB Signaling Pathways

Author

Dai, Chongshan, primary, Ciccotosto, Giuseppe D., additional, Cappai, Roberto, additional, Wang, Yang, additional, Tang, Shusheng, additional, Hoyer, Daniel, additional, Schneider, Elena K., additional, Velkov, Tony, additional, and Xiao, Xilong, additional

Published
2017
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192. Gelofusine Ameliorates Colistin-Induced Nephrotoxicity

Author

Sivanesan, Sivashangarie S., primary, Azad, Mohammad A. K., additional, Schneider, Elena K., additional, Ahmed, Maizbha U., additional, Huang, Jiayuan, additional, Wang, Jiping, additional, Li, Jian, additional, Nation, Roger L., additional, and Velkov, Tony, additional

Published
2017
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193. The thermodynamics of Pr55Gag-RNA interaction regulate the assembly of HIV

Author

Tanwar, Hanumantsingh, Khoo, Keith K., Garvey, Megan, Waddington, Lynne, Leis, Andrew, Hijnen, Marcel, Velkov, Tony, Dumsday, Geoff J., McKinstry, William J., Mak, Johnson, Tanwar, Hanumantsingh, Khoo, Keith K., Garvey, Megan, Waddington, Lynne, Leis, Andrew, Hijnen, Marcel, Velkov, Tony, Dumsday, Geoff J., McKinstry, William J., and Mak, Johnson

Abstract

The interactions that occur during HIV Pr55Gag oligomerization and genomic RNA packagingare essential elements that facilitate HIV assembly. However, mechanistic details ofthese interactions are not clearly defined. Here, we overcome previous limitations in producinglarge quantities of full-length recombinant Pr55Gag that is required for isothermal titrationcalorimetry (ITC) studies, and we have revealed the thermodynamic properties of HIVassembly for the first time. Thermodynamic analysis showed that the binding between RNAand HIV Pr55Gag is an energetically favourable reaction (ΔG<0) that is further enhanced bythe oligomerization of Pr55Gag. The change in enthalpy (ΔH) widens sequentially from: (1)Pr55Gag-Psi RNA binding during HIV genome selection; to (2) Pr55Gag-Guanosine Uridine(GU)-containing RNA binding in cytoplasm/plasma membrane; and then to (3) Pr55Gag-Adenosine(A)-containing RNA binding in immature HIV. These data imply the stepwiseincrements of heat being released during HIV biogenesis may help to facilitate the processof viral assembly. By mimicking the interactions between A-containing RNA and oligomericPr55Gag in immature HIV, it was noted that a p6 domain truncated Pr50Gag Δp6 is less efficientthan full-length Pr55Gag in this thermodynamic process. These data suggest a potentialunknown role of p6 in Pr55Gag-Pr55Gag oligomerization and/or Pr55Gag-RNA interaction duringHIV assembly. Our data provide direct evidence on how nucleic acid sequences and theoligomeric state of Pr55Gag regulate HIV assembly.

Published
2017

198. Investigating the Interaction of Octapeptin A3 with Model Bacterial Membranes

Author

Han, Mei-Ling, primary, Shen, Hsin-Hui, additional, Hansford, Karl A., additional, Schneider, Elena K., additional, Sivanesan, Sivashangarie, additional, Roberts, Kade D., additional, Thompson, Philip E., additional, Le Brun, Anton P., additional, Zhu, Yan, additional, Sani, Marc-Antoine, additional, Separovic, Frances, additional, Blaskovich, Mark A. T., additional, Baker, Mark A., additional, Moskowitz, Samuel M., additional, Cooper, Matthew A., additional, Li, Jian, additional, and Velkov, Tony, additional

Published
2017
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199. Hydrolyzable Poly[Poly(Ethylene Glycol) Methyl Ether Acrylate]–Colistin Prodrugs through Copper-Mediated Photoinduced Living Radical Polymerization

Author

Zhu, Chongyu, primary, Schneider, Elena K., additional, Nikolaou, Vasiliki, additional, Klein, Tobias, additional, Li, Jian, additional, Davis, Thomas P., additional, Whittaker, Michael R., additional, Wilson, Paul, additional, Kempe, Kristian, additional, Velkov, Tony, additional, and Haddleton, David M., additional

Published
2017
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200. From Breast Cancer to Antimicrobial: Combating Extremely Resistant Gram-Negative “Superbugs” Using Novel Combinations of Polymyxin B with Selective Estrogen Receptor Modulators

Author

Hussein, Maytham H., primary, Schneider, Elena K., additional, Elliott, Alysha G., additional, Han, Meiling, additional, Reyes-Ortega, Felisa, additional, Morris, Faye, additional, Blaskovich, Mark A. T., additional, Jasim, Raad, additional, Currie, Bart, additional, Mayo, Mark, additional, Baker, Mark, additional, Cooper, Matthew A., additional, Li, Jian, additional, and Velkov, Tony, additional

Published
2017
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