Phage Display-Derived Peptides and Antibodies for Bacterial Infectious Diseases Therapy and Diagnosis

Abstract

The emergence of antibiotic-resistant-bacteria is a serious public health threat, which prompts us to speed up the discovery of novel antibacterial agents. Phage display technology has great potential to screen peptides or antibodies with high binding capacities for a wide range of targets. This property is significant in the rapid search for new antibacterial agents for the control of bacterial resistance. In this paper, we not only summarized the recent progress of phage display for the discovery of novel therapeutic agents, identification of action sites of bacterial target proteins, and rapid detection of different pathogens, but also discussed several problems of this technology that must be solved. Breakthrough in these problems may further promote the development and application of phage display technology in the biomedical field in the future.

Bacteriophages and their unique components provide limitless resources for exploitation

“…These and several additional studies have emerged demonstrating that phages are an invaluable resource to scientists and that their individual components have a plethora of functions beyond the usage of intact phages for bacterial therapy and gene transduction [for an excellent review, see Salmond and Fineran ( 2015 )]; although new applications for phages even in gene cloning and expression have emerged through the discovery of phage N15's ability to deliver linearized vectors into bacteria, and now also engineered for use in eukaryotic cells (Wong et al, 2023 ). Additional phage applications include the use of their receptor binding proteins for bacterial detection, or engineering intact phages for bacterial viability reporting [using phage cocktails or synthetic approaches to expand host ranges (Sun et al, 2023 )], and even uses in tumor detection, targeted therapeutic delivery (Shen et al, 2023 ), or reducing cancer progression (Sanmukh et al, 2021a , b ); the exploitation of filamentous phages for phage display (Franca et al, 2023 ) traditionally for antibody screening and more recently for antibacterial development (Zhao et al, 2023 ); exogenous addition of phage endolysins (Fischetti, 2011 ; Cahill and Young, 2019 ; Abdelrahman et al, 2021 ) as a method for killing of Gram-positive (Mursalin et al, 2023 ), and more recently, Gram-negative microbes (Gondil et al, 2020 ) [together with outer membrane permeabilizers (Kocot et al, 2023 )]; phage-based vaccines (more on this below) (Palma, 2023 ); and the use of phage depolymerases as adjuvant therapy to disperse microbial biofilms (Topka-Bielecka et al, 2021 ). Bacteria have also retained phage proteins such as their toxins (typically in lysogenic conversion) to help with dissemination (Kumar et al, 2020 ), or permanently adapted phage tail-like structures in Type VI secretions systems for injection of toxic effectors into eukaryotic or bacterial hosts (Leiman et al, 2009 ), or co-opted holins coupled with cell-wall editing enzymes in Type X secretion systems (Palmer et al, 2021 ).…”

Phage Display in Cancer Research: Special Issue Editorial

“…Soon after its birth in 1985, following a short lag period [ 1 , 2 ], the phage display technology enjoyed a tremendous exponential growth, demonstrating its competence and performance in solving numerous challenging problems in material science, bioengineering, and medicine, including cancer research [ 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ] ( Figure 1 ). This Special Issue aims to illustrate the promise of phage display as a universal research tool in cancer research.…”

Reprogramming Filamentous fd Viruses to Capture Copper Ions

“…[17] Metal specific peptide-based binding moieties could be identified by phage display technology introduced by Prof. George P. Smith and his colleagues in mid 80s which lead to a Nobel prize in chemistry in 2018. [18] Phage display technique employs filamentous M13 viruses engineered to display a library of short peptide sequences on P3 tail coat proteins. Structurally and genetically, M13 bacteriophages are very close relatives of fd viruses.…”