Structural and Functional Characterization of Biofilm-Related Proteins of Mycobacterium spp: An in-silico Approach

Abstract

Biofilm-associated infections are characterized by the chronicity, recurrence, and the requirement of a prolonged administration of multiple drugs. Several non-pathogenic and pathogenic species of microorganism including Mycobacteria spp form biofilm. Mycobacterial biofilms present a unique composition. Instead of exopolysaccharides in other bacteria, proteins are essential compounds of the biofilm matrix in mycobacteria. To tackle mycobacterial infections, a detailed understanding of the biofilm-forming mechanisms is crucial. In this present study, all available Mycobacterial proteins involved in the biofilm were selected. Their sequences were retrieved and characterized through the determination of their physicochemical properties, secondary structure, 3D structure, subcellular localization, conserved domain, ubiquitination sites, and virulence potentiality. Furthermore, druggability testing was undertaken after excluding proteins with homology to human proteins to identify possible drug targets. The results showed that they possess functionally important domains and families. All of the selected hypothetical proteins were stable. Six of them were classified as soluble and the remaining as transmembrane proteins. A sole protein was found to lack ubiquitination sites. Additionally, three of these were discovered to be virulent. Moreover, host non-homology results indicated eight pathogen-specific proteins that might be potential therapeutic targets. Among them, D-alanyl-D-alanine carboxypeptidase is a druggable target that is inhibited by beta-lactam antibiotics. The remainder of the proteins were categorized as new targets. 
 In conclusion, this study may increase our knowledge of pathogenesis and host adaptation, drug resistance, and identification of drug and vaccine targets against infections caused by Mycobacteria. It can also guide new research.