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1.
Infect Genet Evol ; 91: 104808, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33737229

RESUMO

The global dissemination of multidrug-resistant Escherichia coli lineages belonging to high- risk clones poses a significant public health threat. Herein we report the identification and genomic profiling of two multidrug-resistant E. coli strains [BL-II-03(2) and BL-II-11(3)] belonging to the O15:H1-D-ST393 (clonal complex 31) worldwide spread clone, isolated from fecal samples of indigenous peoples belonging to two different ethnic groups of remote communities of Brazilian Amazon. Genomic analysis revealed genes and mutations conferring resistance to ß-lactams [blaTEM-1], aminoglycosides [aadA5, aph(3″)-Ib, aph(6)-Id], tetracyclines [tetB], sulfamethoxazole/trimethoprim [sul1, sul2, dfrA17], and fluoroquinolones [gyrA (D87N, S83L), parC (S80I, S57T), parE (L416F)]; and presence of IncQ1, IncFIA, and IncFIB(pB171) plasmids. On the other hand, phylogenomics of globally reported E. coli ST393 assigned E. coli strains BL-II-03(2) and BL-II-11(3) to a cluster comprising human isolates from Australia, Canada, China, Sweden, and United States of America. These results might provide valuable information for understanding dissemination of intercontinental multidrug-resistant clones in remote communities with low levels of antibiotic exposure.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Escherichia coli/isolamento & purificação , Fluoroquinolonas/farmacologia , Escherichia coli/classificação , Escherichia coli/genética , Fezes/microbiologia , Humanos , Indígenas Sul-Americanos , População Rural
2.
Eur J Pharmacol ; 570(1-3): 10-7, 2007 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-17588561

RESUMO

The effects of the alkylaminoalkanethiosulfuric acids (AAATs), new schistosomicidal drugs, on Schistosoma mansoni ATP diphosphohydrolase isoforms, members of the NTPDase family, were analyzed. Pre-incubation of worm adult tegument with AAATs derivatives, with small apolar alkyl groups and an apolar alkane portion of 6 or 8 carbon atoms linked to the amino group, inhibited ATPase activity with a Ki 100-1000 microM. Little inhibition (20%) was observed when ADP was the substrate. The 2-[(tert-butyl)amino]-1-ethanethiosulfuric acid (100 microM) which has a less lipophilic structure, inhibited 28% ATPase and 12% ADPase activities, suggesting that the lipophilicity, although important, is not the only requisite for enzyme activity inhibition. The N-(sec-butyl)-2-bromo-1-octanaminium bromide, which contains a bromide atom instead of thiosulphate, inhibited <10% of the enzyme activity, suggesting the involvement of cysteine residue(s) from S. mansoni ATP diphosphohydrolase isoforms in a mixed disulfide formation. Treatment of parasite tegument with 5 mM iodoacetamide or 1 mM dithiothreitol protected ATPase and ADPase activities against inhibition by AAATs, corroborating the participation of disulfide interchange in the AAATs mechanism. Since S. mansoni ATP diphosphohydrolase isoforms and potato apyrase share structural similarities, the latter enzyme was also tested. ADPase activity from potato apyrase was inhibited by 55%, showing a higher sensitivity to 1 mM AAATs than that shown by ADPase activity from the tegument, while the ATPase activities from both samples showed similar inhibition levels. Furthermore, sulfhydryl reagents protected potato apyrase activity. Therefore, it is possible that both soluble S. mansoni ATP diphosphohydrolase and membrane-associated isoforms are targets for the AAATs.


Assuntos
Apirase/antagonistas & inibidores , Schistosoma mansoni/efeitos dos fármacos , Esquistossomicidas/farmacologia , Ésteres do Ácido Sulfúrico/farmacologia , Adenosina Trifosfatases/metabolismo , Animais , Apirase/metabolismo , Ditiotreitol/farmacologia , Glutationa/farmacologia , Iodoacetamida/farmacologia , Masculino , Camundongos , Schistosoma mansoni/enzimologia , Solanum tuberosum/enzimologia , Reagentes de Sulfidrila/farmacologia
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