Eniyan, K. | Search bioRxiv

bioRxiv2022

A Lysozyme Murein Hydrolase with Broad-spectrum Antibacterial Activity from Enterobacter Phage myPSH1140

Bacteriophages and bacteriophage-derived peptidoglycan hydrolases (endolysins) present promising alternatives for the treatment of infections caused by multi-drug resistant Gram-negative and Gram-positive pathogens. In this study, Gp105, a putative lysozyme murein hydrolase from Enterobacter phage myPSH1140 was characterized in silico, in vitro as well as in vivo using the purified protein. Gp105 contains a T4-type lysozyme-like domain (IPR001165) and belongs to Glycoside hydrolase family 24 (IPR002196). The putative endolysin indeed had strong antibacterial activity against Gram-negative pathogens including E. cloacae, K. pneumoniae, P. aeruginosa, S. marcescens, Citrobacter sp. and A. baumannii. Also, an in vitro peptidoglycan hydrolysis assay showed strong activity against purified peptidoglycans. This study demonstrates the potential of Gp105 to be used as an antibacterial protein to combat Gram-negative pathogens.

microbiology↗

bioRxiv2021

Computational identification and characterization of antigenic properties of Rv3899c of Mycobacterium tuberculosis and its interaction with Human leukocyte antigen (HLA)

Tuberculosis (TB) is the second largest infectious disease that kills 1.2 million people annually worldwide. A rise in drug-resistant TB cases demands continued efforts towards the discovery & development of drugs and vaccines. In the recent past, though novel drugs have been added to the current TB regimen [1], research on new vaccine candidates needs a greater thrust. Secretory proteins of H37Rv are frequently studied for their antigenicity and their scope as protein subunit vaccines decrees further analysis. In this study, Rv3899c of H37Rv emerges as a potential vaccine candidate on its evaluation by several bioinformatics tools. It is a non-toxin, secretory protein with an immunoglobulin-like fold which does not show similarity with a human protein. We found Rv3899c homologs in several mycobacterial species and its antigenic score (0.54) to compare well with the known immunogens such as ESAT-6 (0.56) and Rv1860 (0.52). Structural examination of Rv3899c predicted ten antigenic peptides, an accessibility profile of the antigenic determinants constituting B-cell epitope rich regions and a low Abundance of Antigenic Regions (AAR) value. Significantly, our study shows ESX-2 secretion system proteins and antigenic PE/PPE proteins of H37Rv as the interacting partners of Rv3899c. Further, molecular docking predicted Rv3899c to interact with human leukocyte antigen HLA-DRB1*04:01 through its antigenically conserved motif (RAAEQQRLQRIVDAVARQEPRISWAAGLRDDGTT). Interestingly, the binding affinity was observed to increase on citrullation of its Arg1 residue. Taken together, the computational characterization and predictive information suggest Rv3899c to be a promising TB vaccine candidate, which should be examined and validated experimentally.

immunology↗