Broadening the antibacterial spectrum of histidine kinase autophosphorylation inhibitors via the use of ε-poly-L-lysine capped mesoporous silica-based nanoparticles

Autor: Núria Mas, Lorena Polo, Jerry M. Wells, Ramón Martínez-Máñez, Rui Cao, Laura Miguel-Romero, Ellen H. Stolte, Alberto Marina, Nico Taverne, Nadya Velikova, José Ramón Murguía, Edoardo Zaccaria
Rok vydání: 2016
Předmět:
0301 basic medicine
Histidine Kinase
Lysine
Pharmaceutical Science
Medicine (miscellaneous)
02 engineering and technology
Drug Delivery Systems
Nanotechnology
General Materials Science
Internalization
media_common
biology
Autophosphorylation
021001 nanoscience & nanotechnology
Silicon Dioxide
Anti-Bacterial Agents
Biochemistry
Two-component systems
Drug delivery
Molecular Medicine
0210 nano-technology
media_common.quotation_subject
Biomedical Engineering
Gram negative
Bioengineering
Gram-Positive Bacteria
03 medical and health sciences
In vivo
Gram-Negative Bacteria
QUIMICA ANALITICA
BIOQUIMICA Y BIOLOGIA MOLECULAR
Animals
Humans
Histidine
Host-Microbe Interactomics
PROYECTOS DE INGENIERIA
VLAG
Histidine kinase
fungi
QUIMICA INORGANICA
biology.organism_classification
In vitro
Multi-drug resistance
030104 developmental biology
WIAS
Nanoparticles
Bacteria
Zdroj: Nanomedicine: Nanotechnology, Biology and Medicine
Nanomedicine: Nanotechnology, Biology, and Medicine, 13(2), 569-581
Nanomedicine: Nanotechnology, Biology, and Medicine 13 (2017) 2
RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia
instname
ISSN: 1549-9634
DOI: 10.1016/j.nano.2016.09.011
Popis: [EN] Two-component systems (TCS) regulate diverse processes such as virulence, stress responses, metabolism and antibiotic resistance in bacteria but are absent in humans, making them promising targets for novel antibacterials. By incorporating recently described TCS histidine kinase autophosphorylation inhibitors (HKAIs) into epsilon-poly-L-lysine capped nanoparticles (NPs) we could overcome the Gram negative (Gr(-)) permeability barrier for the HKAIs. The observed bactericidal activity against Gr(-) bacteria was shown to be due to the enhanced delivery and internalization of the HKAIs and not an inhibitory or synergistic effect of the NPs. The NPs had no adverse effects on mammalian cell viability or the immune function of macrophages in vitro and showed no signs of toxicity to zebrafish larvae in vivo. These results show that HKAIs are promising antibacterials for both Gr(-) and Gr + pathogens and that NPs are a safe drug delivery technology that can enhance the selectivity and efficacy of HKAIs against bacteria. (C) 2016 Elsevier Inc. All rights reserved.
This work was funded by FP7 ITN STARS-Scientific Training in Antimicrobial Research Strategies (Contract No. PITN-GA-2009-238490, J.M.W., A.M.), H2020 MSCA IF (AND-659121, N.V.), grant BIO2013-42619-P from the Ministerio de Economia y Competitividad (A.M.), grant from the Spanish Government (Project MAT2015-64139-C4-1-R,N. M., J.R.M, R.M.M.), and a grant from Generalitat Valenciana (Project PROMETEOII/2014/047, N.M.). and Prometeo II/2014/029, A.M.).
Databáze: OpenAIRE
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