Studies on New Delhi Metallo-Beta-Lactamse-1 producing Acinetobacter baumannii isolated from donor swab in a tertiary eye care centre, India and structural analysis of its antibiotic binding interactions.

Gram-negative bacilli, Enterobacteriaceae and Non-fermentors with resistance to carbapenems and metallo beta-lactams are the major cause of concern in clinical problems in current human healthcare. The most highly emerging dreadful Metallo Beta-lactamses is New Delhi metallo-beta-lactamase (blaNDM-1) which confers resistance to carbapenems; susceptible only to colistin and, less consistently to tigecycline, leading to no therapeutic options. In the present study, we demonstrate the effects of cephalosporins and carbepenems on biofilm producing A. baumanii clinical isolate and also to infer the probable inhibitory binding mode through molecular docking studies. The result of MIC on Biofilm producing A. baumanii and the docking analysis results were found to be concordant. Moreover, we also found cephalosporins and carbepenem groups to interact with 162-166 region of blaNDM-1, which is unique for NDM-1 and also documented to be a potential drug targeting region.

Functional characterization of novel mutations in UL54 of ganciclovir resistant HCMV strain using structural analysis.

This study reports the probable impact of the coupled mutations observed in our clinical isolate of HCMV UL54 polymerase, through structural bioinformatics approaches. The reported variant was found to be resistant to Ganciclovir (GCV) as per the clinical records. The presence of Glutamine deletion at 639 (Glu639) and a mis sense mutation of Serine 655 Leucine (Ser655Leu) in UL54 were identified by DNA sequencing and were predicted to lie in the DNA polymerase type-II domain. Docking simulation studies of the phosphorylated forms of Ganciclovir (GCV), Cidofovir (CDV) and Foscarnet (PFA) with the reported mutants showed significant variation in terms of binding affinity and inhibitory constant (Ki) in comparison to wild type UL54. The findings of this study revealed that the observed coupled mutation could potentially induce allosteric effects in the binding pockets of UL54 and thereby alter the drug binding affinity. In specific, it was observed that this coupled mutation could confer changes in the binding affinity of GCV and PFA by altering the binding energies and inhibitory constants to -0.88Kcal/mol and 226.71mM, -5.81Kcal/mol and 54.83µM, respectively, in comparison to Wild Type. On the other hand, CDV showed increased susceptibility for the reported mutant with a binding energy of -6.16Kcal/mol and inhibitory constant of 30.47µM.