Bactericidal Activity of a Cationic Peptide on Neisseria meningitidis

• Published in: Infectious disorders drug targets Vol. 19; no. 4; p. 421
• Main Authors: De-Simone, Salvatore G, Souza, Andre L A, Pina, Jorge L S, Junior, Ivan N, Lourenço, Maria C, Provance, David W
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 2019
• Subjects: Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - pharmacology; Antimicrobial Cationic Peptides - chemical synthesis; Antimicrobial Cationic Peptides - pharmacology; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Neisseria meningitidis - drug effects; Propidium - metabolism; natural immunity; Neisseria meningitidis; cationic peptides; poly-leu; antimicrobial peptide; membrane lysis; cecropin A
• ISSN: 2212-3989
• DOI: 10.2174/1871526518666180816132414

The increasing prevalence of antibiotic resistant bacteria has raised an urgent need for substitute remedies. Antimicrobial peptides (AMPs) are considered promising candidates to address infections by multidrug-resistant bacteria through new mechanisms of action that require a careful evaluation of their performance. Identification of effective AMPs against Neisseria meningitidis, which represents a pathogen of great public health importance worldwide that is intrinsically resistant to some AMPs, such as polymyxin B. A cationic 11-residue peptide (KLKLLLLLKLK), referred to as poly-Leu, was synthesized and its antimeningococcal activity was compared to cecropin A and poly-P (KLKPPPPPKLK) through a variety of assays. Flow cytometry was used to measure propidium iodide uptake by N. meningitidis serotype B as an indicator of the effectiveness of each peptide when added to cultures at different concentrations. The addition of the poly-Leu peptide led to a 90.3% uptake of the dye with an EC50 value of 7.9 µg mL-1. In contrast, uptake was <10% in cells grown in the absence of peptides or with an identical concentration of cecropin and poly-Pro peptides. Electron micrographs indicated that the integrity of the cellular wall and internal membrane was impacted in relation to peptide concentrations, which was confirmed by the detection of released alkaline phosphatase from the periplasmic space due to disruption of the external membrane. Poly-Leu peptide demonstrated definitive antimicrobial activity against N. meningitidis.