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
The genetic diversity from species of the genus Jatropha collected from Costa Rica was analyzed by AFLP (amplified fragments length polymorphism). The study consisted of 114 accessions from 15 populations of 4 differe...The genetic diversity from species of the genus Jatropha collected from Costa Rica was analyzed by AFLP (amplified fragments length polymorphism). The study consisted of 114 accessions from 15 populations of 4 different species: J. curcas, J. costaricensis, J. gossypifolia and J. stevensii. These were collected from different locations in Costa Rica. Three different primers were used, resulting in 428 loci, and they were classified in three categories: unique and double bands (UBD), rare bands (RB) and shared bands (SB). The UBD were excluded for a total of 339 polymorphic loci used for the UPGMA dendrogram and principal component analysis (PCA). The species that obtained the highest average of polymorphic loci was J. curcas, which obtained the highest percentage of polymorphic loci (80.24%), followed by J. gossypifolia (79.35%), J. costaricensis (78.76%), and finally J. stevensii (40.71%). The average for the polymorphic loci was of 69.76%. Thus, the phylogeny of the Jatropha species in Costa Rica was elucidated, showing J. curcas more related to J. stevensii and this one with J. costaricensis, and J. gossypifolia as the most distant member of the genus. For the best of our knowledge this is the first report of a genetic analysis of J. costaricensis and J. stevensii. The obtained molecular evidence showed high levels of polymorphisms in the present study compared with reports from Africa, India, and China. The molecular diversity estimated in our analysis, together with agronomical or morphological data, can be very useful for plant breeding programs, given the importance of Jatropha species in oil production. Interestingly, Central American Jatropha material can be used to increase the genetic base of J. curcas populations localized in Asia and Africa, where reduced genetic diversity has been reported.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.
基金This work was supported by the Vicerrectoría de Investigación of the University of Costa Rica and the National Center for Biotechnological Innovations—CENIBiot,through the project No.111-B2-503 and CB-D1-2010 respectively.
文摘The genetic diversity from species of the genus Jatropha collected from Costa Rica was analyzed by AFLP (amplified fragments length polymorphism). The study consisted of 114 accessions from 15 populations of 4 different species: J. curcas, J. costaricensis, J. gossypifolia and J. stevensii. These were collected from different locations in Costa Rica. Three different primers were used, resulting in 428 loci, and they were classified in three categories: unique and double bands (UBD), rare bands (RB) and shared bands (SB). The UBD were excluded for a total of 339 polymorphic loci used for the UPGMA dendrogram and principal component analysis (PCA). The species that obtained the highest average of polymorphic loci was J. curcas, which obtained the highest percentage of polymorphic loci (80.24%), followed by J. gossypifolia (79.35%), J. costaricensis (78.76%), and finally J. stevensii (40.71%). The average for the polymorphic loci was of 69.76%. Thus, the phylogeny of the Jatropha species in Costa Rica was elucidated, showing J. curcas more related to J. stevensii and this one with J. costaricensis, and J. gossypifolia as the most distant member of the genus. For the best of our knowledge this is the first report of a genetic analysis of J. costaricensis and J. stevensii. The obtained molecular evidence showed high levels of polymorphisms in the present study compared with reports from Africa, India, and China. The molecular diversity estimated in our analysis, together with agronomical or morphological data, can be very useful for plant breeding programs, given the importance of Jatropha species in oil production. Interestingly, Central American Jatropha material can be used to increase the genetic base of J. curcas populations localized in Asia and Africa, where reduced genetic diversity has been reported.
