The emergence of antibiotic resistance in bacteria is a serious threat with enormous social and economic
implications. The distribution of resistance genes/markers through horizontal gene transfer leads to the dissemination
of resistant strains in different parts of the world. The resistant bacteria acquire the ability to overcome resistance by
different modes amongst which the expression of β-lactamases is a major factor. The β-lactamase enzymes cleave the
amide bond of the β-lactam antibiotics, which constitute about one-third of the antibiotics used all over the world. In a
quest to control the spread of resistant bacteria, advanced generations of antibiotics are used either alone or in combination
with inhibitors. However, these antibiotics and inhibitors also contain β-lactam ring in their structure and hence
are prone to be hydrolyzed by β-lactamase enzymes in the near future. Thus, the severity of the problem is manifested
due to the paucity of novel non-β-lactam core containing antibiotics in the drug development stage. One approach to
overcome these shortcomings is to use peptide-based inhibitors. Here, we describe the potential use of phage display
technique to screen commercially available libraries to pan against β-lactamase enzymes. The main advantage of using
peptide-based inhibitors is that the bacteria will not be able to recruit pre-existing defense mechanisms and it will take
a long time to evolve a new mechanism in its defense against peptide-based inhibitors.
Keywords: Antibiotic resistance, antimicrobial peptides, peptide-based inhibitors, phage display, gram-negative bacteria.
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