ABSTRACT
Emergence of antimicrobial resistance mediated through New Delhi metallo-ß-lactamases (NDMs) is a serious therapeutic challenge. Till date, 16 different NDMs have been described. In this study, we report the molecular and structural characteristics of NDM-5 isolated from an Escherichia coli isolate (KOEC3) of bovine origin. Using PCR amplification, cloning and sequencing of full blaNDM gene, we identified the NDM type as NDM-5. Cloning of full gene in E. coli DH5α and subsequent assessment of antibiotic susceptibility of the transformed cells indicated possible role of native promoter in expression blaNDM-5. Translated amino acid sequence had two substitutions (Val88Leu and Met154Leu) compared to NDM-1. Theoretically deduced isoelectric pH of NDM-5 was 5.88 and instability index was 36.99, indicating a stable protein. From the amino acids sequence, a 3D model of the protein was computed. Analysis of the protein structure elucidated zinc coordination and also revealed a large binding cleft and flexible nature of the protein, which might be the reason for broad substrate range. Docking experiments revealed plausible binding poses for five carbapenem drugs in the vicinity of metal ions. In conclusion, results provided possible explanation for wide range of antibiotics catalyzed by NDM-5 and likely interaction modes with five carbapenem drugs.
ABSTRACT
PIP: Prominent women from Korea, Nepal, India, Philippines, Thailand, and Afghanistan discuss family planning attitudes in broad terms. Educated women in urban areas make decisions regarding birth control and family size, but the tradition in most developing countries is that of the man in the authority role. Family planning is intrinsically a joint decision. Obligations to family and family lineage prohibit family planning. In the Philippines, Catholicism is the dominant religion and because of population density, encourages family planning. For economic and social reasons, rural families prefer more children. The changing role of women to include jobs and education will have a positive effect on family planning. The representative from Nepal points out that it is necessary to have family planning in order to have changing women's roles. Rather than emphasizing smaller family size, it is recommended by concensus, that family planners communicate health and nutritional benefits for each individual child.^ieng
