ABSTRACT
Hospital and agriculture wastewater is mostly responsible for causing environmental pollution by spreading un-metabolized antibiotics and resistant bacteria, especially in Bangladesh. Here, we studied the influence of the most frequently prescribed antibiotic, fluoroquinolone (~72%), on the development of antibiotic resistance in Escherichia coli. Out of 300, 24 ciprofloxacin resistant E. coli isolates were selected for the study that showed the MBC(100) higher than expected (600 µg/mL). Here, we profiled plasmid, sequenced gyr genes, screened mutations and analyzed the effect of mutation on drug-protein interaction through molecular docking approach. We found that (1) out of 10, most of them (n = 7) had large plasmid(s); (2) all ciprofloxacin-resistant isolates had gyrA double mutations (S83L and D87Y); (3) no isolate had qnr gene; and (4) docking of ciprofloxacin with DNA gyrase A subunit suggests that acquisition of double mutation leads to alteration of the ciprofloxacin binding pocket.
Subject(s)
Anti-Bacterial Agents/pharmacology , Ciprofloxacin/pharmacology , Drug Resistance, Bacterial , Escherichia coli/classification , Escherichia coli/drug effects , Wastewater/microbiology , Anti-Bacterial Agents/metabolism , Bangladesh , Ciprofloxacin/metabolism , DNA Gyrase/genetics , DNA, Bacterial/chemistry , DNA, Bacterial/genetics , Escherichia coli/genetics , Escherichia coli/isolation & purification , Hospitals , Microbial Sensitivity Tests , Microbial Viability/drug effects , Molecular Sequence Data , Mutation, Missense , Plasmids/analysis , Sequence Analysis, DNAABSTRACT
A total of 1106 stool samples collected from diarrhoea patients admitted to Dhaka hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh, during January-December 2008 were analysed for the presence of rotavirus-specific RNA by PAGE. The group B-specific RNA migration pattern was detected in 26 patients (2.4%) and group A-specific pattern in 259 patients (23.4%). Clinical data from group A and group B rotavirus-infected patients indicated that episodes did not differ much in the prevalence of diarrhoea, number of stools, outcome or differences in gender. However, abdominal pain was more common in group B rotavirus infections (36 vs 15%, P=0.02) and the virus was responsible for more severe dehydration compared with group A-infected patients (12 vs 3%, P=0.04). Sequence analyses of VP4, VP7 and NSP2 indicated that an Indian-Bangladeshi lineage of the virus, which is different from both the prototype (Chinese) lineage and from the animal group B rotaviruses, has been circulating in Bangladesh. Continuous monitoring of group B rotaviruses both in hospitals and in the community will be helpful to determine the true burden of group B rotaviruses.
Subject(s)
Diarrhea/pathology , Diarrhea/virology , Rotavirus Infections/pathology , Rotavirus Infections/virology , Rotavirus/classification , Rotavirus/isolation & purification , Adolescent , Adult , Aged , Aged, 80 and over , Bangladesh , Child , Cluster Analysis , Electrophoresis, Polyacrylamide Gel , Feces/virology , Humans , Middle Aged , Molecular Sequence Data , Phylogeny , RNA, Viral/genetics , Rotavirus/genetics , Sequence Analysis, DNA , Young AdultABSTRACT
Dengue virus, a member of the flavivirus family, is a mosquito-borne viral pathogen for which any specific treatment or control of infection by vaccination is yet to be conclusive. The envelope glycoprotein, E, mediates viral entry by membrane fusion. Elucidation of post-translational modification sites in E protein followed by sequence alignment produced stretches of residues which are conserved in most of the members of flaviviruses. Presence of protein kinase A (PKA) and protein kinase G (PKG) phosphorylation sites predicts that E protein may activate PKA and PKG through phosphorylation which is responsible for inhibition of platelet activation, and thereby causing thrombocytopenia. Here, we attempt to decipher the novel role of Dengue virus E protein in pathogenesis.
