Mycobacterial infections result in huge damage to public health and economy each year because of the alarming emergence of extensively drug-resistant strains of Mycobacterium tuberculosis (WHO, 2019). Mycobacteria have long known to be intrinsically resistant to β-lactam antibiotics. Β-lactamases are enzymes those protect bacterial cells by hydrolyzing β-lactam ring of antibiotics making them ineffective. Class-A β-lactamases have a conserved structural domain called omega loop (RLDRWETELNEAIPGDARD) participating in catalytic activity being a part of the drug-binding pocket of the enzyme. In this work we have attempted to design and characterize some peptides against the omega-loop of class A β-lactamases to reverse antimicrobial resistance in bacteria. Primarily, about 100 peptides were designed against the conserved sequence of omega-loop of class A β-lactamases. The peptides sequences were subjected to different bioinformatics tool and finally, 10 peptides were synthesized by Fmoc Solid-Phase Synthesis Peptide (SPPS) strategy (J.M. Palomo, 2014). Whole-cell phenotypic evaluations were done to ascertain the hydrolytic potential of pbad-blatem1 (class A β-lactamases) against different β-lactam antibiotics in presence of all the synthesized peptides in different bacteria (E. Coli CS109, Mycobacterium smegmatis and Mycobacterium tuberculosis H37Rv) and we observed a significant decreased level of hydrolytic activity of blatem1 in the presence of peptides. Thus, the study may explore the role of peptides in masking of omega-loop facilitating β-lactams to kill the bacteria.
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