Mutations in gyrA are the primary cause of quinolone resistance encountered in gram-negative clinical isolates. The prospect of this work was to analyze the role of gyrA mutations in eliciting high quinolone resistance in uropathogenic E.coli (UPEC) through molecular docking studies. Quinolone susceptibility testing of 18 E.coli strains isolated from UTI patients revealed unusually high resistance level to all the quinolones used; especially norfloxacin and ciprofloxacin. The QRDR of gyrA was amplified and sequenced. Mutations identified in gyrA of E.coli included Ser83Leu, Asp87Asn and Ala93Gly/Glu. Contrasting previous reports, we found Ser83Leu substitution in sensitive strains. Strains with S83L, D87N and A93E (A15 and A26) demonstrated norfloxacin MICs ≥1024mg/L which could be proof that Asp87Asn is necessary for resistance phenotype. Resistance to levofloxacin was comparatively lower in all the isolates. Docking of 4 quinolones (ciprofloxacin, ofloxacin, levofloxacin and norfloxacin) to normal and mutated E.coli gyrase A protein demonstrated lower binding energies for the latter, with significant displacement of norfloxacin in the mutated GyrA complex and least displacement in case of levofloxacin.
Melamine is a nitrogenous organic compound containing high amounts of nitrogen, which is interpreted as high protein in various standard protein measuring tests, therefore added to foods to boost the protein content. Illegal addition of melamine has been in practice by food manufacturers, which leads to toxicity and stone formation in kidneys of individuals consuming melamine-contaminated milk products. A focused and thorough structured search of bibliographic databases for peer-reviewed researches reported in the literature was carried out with a focused attention on melamine contamination, associated health risks, and the role of gut microbiota. The overall outcomes of the research and review articles pertaining to searched keywords along with analysis of the interventions have been described employing a deductive qualitative content analysis approach. Current review focuses on the various health risks associated with consumption of melamine-contaminated foods and the need to develop better and effective methods for its testing. Moreover, the importance of gut microbiota in mediating toxicity due to melamine has also been discussed as there is a link between toxicity and activities of gut microbiota.
Melamine adulteration of food is a public health concern. It has been seen that melamine causes disease in many organs. Melamine-induced kidney disease is a well-recognized clinicopathological entity. Inflammation is thought to be important in melamine-induced pathology. Melamine is expected to bind with albumin because it has a positive charge. Albumin binds arachidonic acid. So if binding of melamine with albumin takes place, it has the potential to displace arachidonic acid from the albumin bound state. This phenomenon may be the source of mediators of inflammation in the melamine exposure state. This aspect is investigated in the present study by docking and molecular dynamics simulation. It is observed that melamine binds with some known arachidonic acid binding sites of albumin. This can lead to formation of more free arachidonic acid. It is also observed that melamine does not bind with extracellular signal regulated kinase 2 (ERK2). Therefore, the signal transduction mediated process involving ERK2 is not a likely mechanism of melamine-induced inflammation. Therefore, we think that an increased free arachidonic acid level may contribute more to inflammation in the melamine exposure state.
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