A Thermostable, Modified Cathelicidin-Derived Peptide With Enhanced Membrane-Active Activity Against Salmonella enterica serovar Typhimurium

Abstract

Foodborne illness caused by consumption of food contaminated with Salmonella is one of the most common causes of diarrheal disease and affects millions of people worldwide. The rising emergence and spread of antimicrobial resistance, especially in some serotypes of Salmonella, has raised a great awareness of public health issues worldwide. To ensure safety of the food processing chain, the development of new food preservatives must be expedited. Recently, thermal- and pH-stable antimicrobial peptides have received much attention for use in food production, and represent safe alternatives to chemical preservatives. A 12-mer cathelicidin-derived, α-helical cationic peptide, P7, displayed rapid killing activity, against strains of drug-resistant foodborne Salmonella enterica serovar Typhimurium and its monophasic variant (S. enterica serovar 4,5,12:i:-) and had minimal toxicity against mouse fibroblast cells. P7 tended to form helical structure in the membrane-mimic environments as evaluated by circular dichroism (CD) spectroscopy. The action mode of P7 at the membrane-level was affirmed by the results of flow cytometry, and confocal, scanning and transmission electron microscopy. P7 killed bacteria through binding to bacterial membranes, penetration and the subsequent accumulation in S. enterica serovar Typhimurium cytoplasm. This induced membrane depolarization, permeabilization, and sequential leakage of intracellular substances and cell death. Except for sensitivity to proteolytic digestive enzymes, P7 maintained its inhibitory activity against S. enterica serovar Typhimurium in the presence of different conditions [various salts, extreme pHs and heat (even at 100°C)]. Moreover, the peptide is unlikely to induce bacterial resistance in vitro. Taken together, this study demonstrated that the membrane-permeabilizing P7 peptide has much potential as a new antimicrobial agent for use in food processing and preservation.

Synthesis and Synergistic Antimicrobial Efficacy of Covalent Conjugates Composed of Epsilon-Poly-l-lysine and Beta-Lactam Antibiotics

“…Rapid-responsive antimicrobial ability, which can correspond to a short response time, is a crucial factor in reducing the risks of drug resistance. − Therefore, it is essential to consider both the required concentration and response time when assessing antimicrobial ability. In this section, a plate counting test was conducted to compare the antimicrobial ability of different drugs within a limited time frame.…”

Combined effect of SAR-endolysin LysKpV475 with polymyxin B and Salmonella bacteriophage phSE-5

“…K. pneumoniae ATCC BAA-2146 has been shown to be resistant to several antibiotics [ 61 62 ] and has about 36 chromosomal and plasmid genes associated with antibiotic resistance [ 61 ], and S . enterica Typhimurium ATCC 13311 is a reference bacteria commonly used as a MDR strain [ 63 64 ]. To our knowledge, this study is the first report of MDR in Enterobacter cloacae ATCC 35030 and P2224.…”

Salmonellosis: An Overview of Epidemiology, Pathogenesis, and Innovative Approaches to Mitigate the Antimicrobial Resistant Infections

“…Similarly, the screening of six different AMPs (KLK and KLK1) derived from flesh fly larva, BmKn-2, and BmKn-22 derived from scorpion venom, and Pug-1 and Pug-4 derived from pomegranate fruit), against eight multidrug-resistant Salmonella isolates showed that BmKn-2 derived from scorpion venom has the highest and most potent antibacterial activity against all isolates and the highest inhibition of Salmonella biofilm formation compared with other peptides [321]. Another in vitro study determining the antimicrobial activity of the modified thermostable cathelicidin-derived peptide, P7, against drug-resistant S. Typhimurium showed that P7 decreased the S. Typhimurium viable cells to more than 10 3 and 10 4 cfu/mL within 2 to 4 h, respectively, and also demonstrated complete clearance of Salmonella 24 h post incubation [322]. Furthermore, it was reported that AMP (Microcin J25) could significantly reduce the infection rate of Salmonella CVCC519 by approximately 30% in challenged Arbor Acres male broiler chickens at day 42 compared to non-treated birds [183].…”