Antimicrobial antibodies by phage display: Identification of antibody-based inhibitor against mycobacterium tuberculosis isocitrate lyase. (October 2022)

• Record Type: Journal Article
• Authors: Ch'ng, Angela Chiew Wen; Schepergerdes, Lena; Choong, Yee Siew; Hust, Michael; Lim, Theam Soon
• Is Part Of: Molecular immunology. Volume 150(2022)
• Page Start: 47
• Page End: 57
• Publication Date: 2022-10
• Subjects: Isocitrate lyase -- Inhibitor -- Enzymatic Assay -- scFv -- Phage Display -- Monoclonal Antibodies; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2022.08.005
• Languages: English
• ISSNs: 0161-5890

Abstract

Abstract: The increasing incidence reports of antibiotic resistance highlights the need for alternative approaches to deal with bacterial infections. This brought about the idea of utilizing monoclonal antibodies as an alternative antibacterial treatment. Majority of the studies are focused on developing antibodies to bacterial surface antigens, with little emphasis on antibodies that inhibit the growth mechanisms of a bacteria host. Isocitrate lyase (ICL) is an important enzyme for the growth and survival of Mycobacterium tuberculosis (MTB) during latent infection as a result of its involvement in the mycobacterial glyoxylate and methylisocitrate cycles. It is postulated that the inhibition of ICL can disrupt the life cycle of MTB. To this extent, we utilized antibody phage display to identify a single chain fragment variable (scFv) antibody against the recombinant ICL protein from MTB. The soluble a-ICL-C6 scFv clone exhibited good binding characteristics with high specificity against ICL. More importantly, the clone exhibited in vitro inhibitory effect with an enzymatic assay resulting in a decrease of ICL enzymatic activity. In silico analysis showed that the scFv-ICL interactions are driven by 23 hydrogen bonds and 13 salt bridges that might disrupt the formation of ICL subunits for the tertiary structure or the formation of active site β domain. However, further validation is necessary to confirm if the isolated clone is indeed a good inhibitor against ICL for application against MTB. Highlights: Recombinant monoclonal antibodies against Mycobacterium tuberculosis Isocitrate Lyase. Inhibition of ICL enzymatic activity by monoclonal scFv. Antibodies as alternatives to antibiotics.