Metallo-β-lactamases are bacterial zinc-dependent enzymes involved in the hydrolysis of β-lactamic antibiotics representing the main cause of bacterial resistance to carbapenems, drugs of last resort for treating in...Metallo-β-lactamases are bacterial zinc-dependent enzymes involved in the hydrolysis of β-lactamic antibiotics representing the main cause of bacterial resistance to carbapenems, drugs of last resort for treating infections caused by multiresistant bacteria. We elaborated the hypothesis that it is possible to inhibit the enzymatic activity of metallo-β-lactamases by lowering the availability of zinc in the extracellular medium using metal chelating agents such as EDTA carried on nanoparticles. Chitosan, as linear cationic polysaccharide is frequently used in biomedical and pharmaceutical applications, has been studied as a biocompatible encapsulating agent in drug delivery systems and is an ideal transport agent for bioactive molecular complexes in antibiotic applications due to its ability to associate with negatively charged substances. We developed novel nanoparticles using chitosan as a transport matrix for β-lactamic antibiotics. Nanoparticles were synthesized according to the ion gelation method using tripolyphosphate as crosslinking agent. Nanoparticles were functionalized by the adsorption of EDTA, which acts as complexifying agent for Zn2+ ions causing inhibition of metallo-β-lactamases activity. We evaluate the antimicrobial effects of EDTA-functionalized nanoparticles with an imipenem cargo on the clinical isolate P. aeruginosa AG1, a carbapenem-resistant high-risk clone ST-111 carrying both blaIMP-18 and blaVIM-2 metallo-β-lactamases genes.展开更多
EDITOR'S NOTE: From August 11 through 21, 2005, Fernando Garcia, a reporter of Spain's ABC newspaper, undertook a reporting tour of Tibet at the invitation of China. After he returned home, Interviu, a Spanish...EDITOR'S NOTE: From August 11 through 21, 2005, Fernando Garcia, a reporter of Spain's ABC newspaper, undertook a reporting tour of Tibet at the invitation of China. After he returned home, Interviu, a Spanish magazine, carried his story titled Viejo Tibet, Nuevos Tibetanos. Following is his story translated from its Chinese version.展开更多
基金the Inter-University Fund for Higher Education(FEES)at the National Council of Rectors(CONARE)for financial support to this project through grant agreement No ACUERDO-VI-171-2014
文摘Metallo-β-lactamases are bacterial zinc-dependent enzymes involved in the hydrolysis of β-lactamic antibiotics representing the main cause of bacterial resistance to carbapenems, drugs of last resort for treating infections caused by multiresistant bacteria. We elaborated the hypothesis that it is possible to inhibit the enzymatic activity of metallo-β-lactamases by lowering the availability of zinc in the extracellular medium using metal chelating agents such as EDTA carried on nanoparticles. Chitosan, as linear cationic polysaccharide is frequently used in biomedical and pharmaceutical applications, has been studied as a biocompatible encapsulating agent in drug delivery systems and is an ideal transport agent for bioactive molecular complexes in antibiotic applications due to its ability to associate with negatively charged substances. We developed novel nanoparticles using chitosan as a transport matrix for β-lactamic antibiotics. Nanoparticles were synthesized according to the ion gelation method using tripolyphosphate as crosslinking agent. Nanoparticles were functionalized by the adsorption of EDTA, which acts as complexifying agent for Zn2+ ions causing inhibition of metallo-β-lactamases activity. We evaluate the antimicrobial effects of EDTA-functionalized nanoparticles with an imipenem cargo on the clinical isolate P. aeruginosa AG1, a carbapenem-resistant high-risk clone ST-111 carrying both blaIMP-18 and blaVIM-2 metallo-β-lactamases genes.
文摘EDITOR'S NOTE: From August 11 through 21, 2005, Fernando Garcia, a reporter of Spain's ABC newspaper, undertook a reporting tour of Tibet at the invitation of China. After he returned home, Interviu, a Spanish magazine, carried his story titled Viejo Tibet, Nuevos Tibetanos. Following is his story translated from its Chinese version.
