Antibacterial and antibiofilm activities of novel antimicrobial peptides against multidrug-resistant enterotoxigenic escherichia coli
Journal
International Journal of Molecular Sciences
Journal Volume
22
Journal Issue
8
Date Issued
2021
Author(s)
Abstract
Post-weaning diarrhea due to enterotoxigenic Escherichia coli (ETEC) is a common disease of piglets and causes great economic loss for the swine industry. Over the past few decades, decreasing effectiveness of conventional antibiotics has caused serious problems because of the growing emer-gence of multidrug-resistant (MDR) pathogens. Various studies have indicated that antimicrobial peptides (AMPs) have potential to serve as an alternative to antibiotics owing to rapid killing action and highly selective toxicity. Our previous studies have shown that AMP GW-Q4 and its derivatives possess effective antibacterial activities against the Gram-negative bacteria. Hence, in the current study, we evaluated the antibacterial efficacy of GW-Q4 and its derivatives against MDR ETEC and their minimal inhibition concentration (MIC) values were determined to be around 2~32 ?g/mL. Among them, AMP Q4-15a-1 with the second lowest MIC (4 ?g/mL) and the highest minimal hemolysis concentration (MHC, 256 ?g/mL), thus showing the greatest selectivity (MHC/MIC = 64) was selected for further investigations. Moreover, Q4-15a-1 showed dose-dependent bactericidal activity against MDR ETEC in time–kill curve assays. According to the cellular localization and membrane integrity analyses using confocal microscopy, Q4-15a-1 can rapidly interact with the bacterial surface, disrupt the membrane and enter cytosol in less than 30 min. Minimum biofilm eradication concentration (MBEC) of Q4-15a-1 is 4× MIC (16 ?g/mL), indicating that Q4-15a-1 is effective against MDR ETEC biofilm. Besides, we established an MDR ETEC infection model with intestinal porcine epithelial cell-1 (IPEC-1). In this infection model, 32 ?g/mL Q4-15a-1 can completely inhibit ETEC adhesion onto IPEC-1. Overall, these results suggested that Q4-15a-1 may be a promising antibacterial candidate for treatment of weaned piglets infected by MDR ETEC. ? 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Subjects
antiinfective agent; pore forming cytotoxic protein; animal; bacterium adherence; biofilm; drug effect; enterotoxigenic Escherichia coli; Escherichia coli infection; genetics; microbial sensitivity test; microbiology; multidrug resistance; pathogenicity; pathology; pig; swine disease; veterinary medicine; Animals; Anti-Bacterial Agents; Bacterial Adhesion; Biofilms; Drug Resistance, Multiple, Bacterial; Enterotoxigenic Escherichia coli; Escherichia coli Infections; Microbial Sensitivity Tests; Pore Forming Cytotoxic Proteins; Swine; Swine Diseases
SDGs
Other Subjects
antiinfective agent; fluorescent dye; gw q 4; gw q 4a; polypeptide antibiotic agent; q 4 15; q 4 15 1; q 4 15 2; q 4 15a; q 4 15a 1; q 4 15a 2; q 4-15 2; unclassified drug; antiinfective agent; pore forming cytotoxic protein; animal cell; antibacterial activity; antibiofilm activity; Article; bacterial infection; bacterial membrane; bacterial strain; bactericidal activity; bacterium adherence; cell adhesion; cell viability assay; cellular distribution; concentration response; confocal microscopy; controlled study; cytosol; drug efficacy; drug potency; drug screening; enterotoxigenic Escherichia coli; epithelium cell; Escherichia coli infection; hemolytic concentration; inhibitory concentration; IPEC-1 cell line; IPEC-J2 cell line; membrane damage; minimum bactericidal concentration; minimum biofilm eradication concentration; minimum inhibitory concentration; multidrug resistance; nonhuman; therapeutic index; transmission electron microscopy; animal; biofilm; drug effect; enterotoxigenic Escherichia coli; Escherichia coli infection; genetics; microbial sensitivity test; microbiology; multidrug resistance; pathogenicity; pathology; pig; swine disease; veterinary medicine; Animals; Anti-Bacterial Agents; Bacterial Adhesion; Biofilms; Drug Resistance, Multiple, Bacterial; Enterotoxigenic Escherichia coli; Escherichia coli Infections; Microbial Sensitivity Tests; Pore Forming Cytotoxic Proteins; Swine; Swine Diseases
Type
journal article