Inhibition of multidrug resistant Listeria monocytogenes by peptides isolated from combinatorial phage display libraries

Abstract

The aim of the study was to isolate and characterize novel antimicrobial peptides from peptide phage library with antimicrobial activity against multidrug resistant Listeria monocytogenes. Combinatorial phage-display library was used to affinity select peptides binding to the cell surface of multidrug resistant L. monocytogenes. After several rounds of affinity selection followed by sequencing, three peptides were revealed as the most promising candidates. Peptide L2 exhibited features common to antimicrobial peptides (AMPs), and was rich in Asp, His and Lys residues. Peptide L3 (NSWIQAPDTKSI), like peptide L2, inhibited bacterial growth in vitro, without any hemolytic or cytotoxic effects on eukaryotic cells. L1 peptide showed no inhibitory effect on Listeria. Structurally, peptides L2 and L3 formed random coils composed of α-helix and β-sheet units. Peptides L2 and L3 exhibited antimicrobial activity against multidrug resistant isolates of L. monocytogenes with no haemolytic or toxic effects. Both peptides identified in this study have the potential to be beneficial in human and veterinary medicine.

Reassessing the Host Defense Peptide Landscape

“…For instance, a phage display approach was used to identify peptides capable of binding to the cell surface of E. coli resulting in a novel antibacterial peptide sequence with activity against both E. coli and P. aeruginosa , although the resultant peptide was unfortunately only moderately active and did not inhibit other tested bacteria (Rao et al, 2013). A similar strategy was employed to identify AMPs with selective activity against Listeria monocytogenes (Flachbartova et al, 2016). Furthermore, phage display has successfully identified peptides with antiviral (Ojeda et al, 2016) and antifungal activity (de Oliveira et al, 2016) demonstrating the utility of such a technique to explore other activity landscapes within the chemical space of HDPs.…”

Anti-Biofilm Strategies: A Focused Review on Innovative Approaches

“…Then, phages that did not bind efficiently to the target are washed, while strongly phage-binding targets are eluted by different methods. The phage display technique has been used to find peptides able to detect enzymes, whole eukaryotic and prokaryotic cells, including MDR strains, and assess if they presented microbicidal activities [266][267][268][269]. In addition, it has been observed that foreign peptides can be modified in their conformation on the phage surfaces and resistance to chemical-physical environment compared to the wild-type [270,271].…”

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

“…Listeriosis is highly lethal and has been associated with foodborne epidemics over the past decade [ 64 ]. Z. Flachbartova et al used the phage-display random-peptide library Ph.D.-12 to target MDR L. monocytogenes [ 23 ]. The selected peptides (L2 and L3) showed antibacterial activities against L. monocytogenes , and their MIC values were both 30 µM.…”