Role of hinge motion and ATP dynamics in factors for inversion stimulation FIS protein deduced while targeting drug resistant Orientia tsutsugamushi.

Orientia tsutsugamushi, the causative agent of scrub typhus has been found resistant to various classes of antibiotics such as penicillins, gentamycin and cephalosporins. Review of current literature suggests that the prevalence of scrub typhus has increased globally. Therefore, the current study has aimed at exploring the genome of O. tsutsugamushi to identify potential drug target proteins that can be used for developing novel antibiotics against the pathogen. Subtractive proteomics approach has revealed FIS as a potential drug target protein involved in two component system (TCS), a signaling pathway crucial for bacteria to survive and adjust in changing environmental conditions. Molecular docking studies have revealed compound-356 (CHEMBRIDGE-10040641-3710.356) as a potential inhibitor in both chains A and B of the FIS protein. Simulation results suggest that the docked complex has remained stable and compact throughout the 200 ns run. Significant conformational changes including the hinge motion was observed in the DNA binding domain. Furthermore, the presence of salt bridge between GLU910 and ARG417, rearrangement of interaction residues and displacement of ATP in the central AAA + domain upon binding to the inhibitor were also observed playing a role in stabilizing the protein structure.

Genome re-seqeunce and analysis of Burkholderia glumae strain AU6208 and evidence of toxoflavin: A potential bacterial toxin.

Burkholderia glumae, the primary causative agent of bacterial panicle blight in rice, has been reported as an opportunistic pathogen in patients with chronic infections. This study aimed to re-sequence the clinical isolate B. glumae strain AU6208 and comparatively analyze its genome using B. glumae strain BGR1 from rice plant as the reference. Re-sequencing results revealed that the genome of strain AU6208 comprised 96 contigs corresponding to a 6.1 Mbp genome of the strain AU6208, with 5322 coding sequences and 68.2 % GC content; this is much larger compared to the genome previously sequenced by us and described by Seo et al (2015), which was reported to be 4.1 Mbp comprising >1200 contigs, 4361 coding sequences, and 67.31 % GC content. Moreover, this updated genome shares >80 % identity to the 7.2 Mbp genome of BGR1, which encodes 6491 coding sequences and has 68.3 % GC content. Further computational analysis revealed that the strain AU6208 encodes several bacteriocin biosynthesis genes, antibiotic, as well as virulent genes such as toxoflavin genes, which included 425 specialty genes and 12 toxoflavin genes. Upon further characterization, 12 toxoflavins (ToxA, B, C, D, E, F, G, H, I, J, TofI, and TofR) were found in AU6208 with 70-100 % sequence, family, and domain similarity with that of BGR1. Upon comparison with BGR1, the structural characterizations of selected toxoflavin genes (ToxB, ToxC, ToxG, H, and TofI) revealed variations in 2D and 3D structures such as differences in α-helix, ß-sheets, loops, physiological properties of proteins, RMSD values, etc. These variations may play significant role in different mode of action in different hosts thereby indicating that in addition to their respective hosts, toxoflavins could also contribute to exploit other hosts across the kingdom. In addition to understanding the epidemiology of strain AU6208, this updated genomics data will also unfold the pathogenicity of bacteria in diversity of various hosts and anti-virulence.