Generic placeholder image

Infectious Disorders - Drug Targets


ISSN (Print): 1871-5265
ISSN (Online): 2212-3989

Research Article

Bactericidal Activity of a Cationic Peptide on Neisseria meningitidis

Author(s): Salvatore G. De-Simone*, Andre L.A. Souza, Jorge L.S. Pina, Ivan N. Junior, Maria C. Lourenço and David W. Provance

Volume 19, Issue 4, 2019

Page: [421 - 427] Pages: 7

DOI: 10.2174/1871526518666180816132414

Price: $65


Background: 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.

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: Poly-Leu peptide demonstrated definitive antimicrobial activity against N. meningitidis.

Keywords: Neisseria meningitidis, antimicrobial peptide, membrane lysis, natural immunity, cecropin A, poly-leu, cationic peptides.

Graphical Abstract
Halperin, S.A.; Bettinger, J.A.; Greenwood, B.; Harrison, L.H.; Jelfs, J.; Ladhani, S.N.; McIntyre, P.; Ramsay, M.E.; Sáfadi, M.A. The changing and dynamic epidemiology of meningococcal disease. Vaccine, 2012, 30(2)(Suppl. 2), B26-B36.
[] [PMID: 22178525]
Brouwer, M.C.; van de Beek, D. Epidemiology of community-acquired bacterial meningitis. Curr. Opin. Infect. Dis., 2018, 31(1), 78-84.
[] [PMID: 29176349]
MacNeil, J.R.; Blain, A.E.; Wang, X.; Cohn, A.C. Current epidemiology and trends in meningococcal disease-United States, 1996-2015. Clin. Infect. Dis., 2017.
[PMID: 29126310]
Rosenstein, N.E.; Perkins, B.A.; Stephens, D.S.; Popovic, T.; Hughes, J.M. Meningococcal disease. N. Engl. J. Med., 2001, 344(18), 1378-1388.
[] [PMID: 11333996]
Read, R.C. Neisseria meningitidis; clones, carriage, and disease. Clin. Microbiol. Infect., 2014, 20(5), 391-395.
[] [PMID: 24766477]
AlMatar, M.; Makky, E.A.; Yakıcı, G.; Var, I.; Kayar, B.; Köksal, F. Antimicrobial peptides as an alternative to anti-tuberculosis drugs. Pharmacol Res, 2017. S1043-6618(17), 31051-31054.
Nuti, R.; Goud, N.S.; Saraswati, A.P.; Alvala, R.; Alvala, M. Antimicrobial Peptides: A promising therapeutic strategy in tackling antimicrobial resistance. Curr. Med. Chem., 2017, 24(38), 4303-4314.
[] [PMID: 28814242]
Jorgensen, J.H.; Crawford, S.A.; Fiebelkorn, K.R. Susceptibility of Neisseria meningitidis to 16 antimicrobial agents and characterization of resistance mechanisms affecting some agents. J. Clin. Microbiol., 2005, 43(7), 3162-3171.
[] [PMID: 16000430]
Geörg, M.; Maudsdotter, L.; Tavares, R.; Jonsson, A.B. Meningococcal resistance to antimicrobial peptides is mediated by bacterial adhesion and host cell RhoA and Cdc42 signalling. Cell. Microbiol., 2013, 15(11), 1938-1954.
[] [PMID: 23834289]
Peak, I.R.; Jennings, C.D.; Jen, F.E.; Jennings, M.P. Role of Neisseria meningitidis PorA and PorB expression in antimicrobial susceptibility. Antimicrob. Agents Chemother., 2014, 58(1), 614-616.
[] [PMID: 24145542]
Tzeng, Y.L.; Ambrose, K.D.; Zughaier, S.; Zhou, X.; Miller, Y.K.; Shafer, W.M.; Stephens, D.S. Cationic antimicrobial peptide resistance in Neisseria meningitidis. J. Bacteriol., 2005, 187(15), 5387-5396.
[] [PMID: 16030233]
Tzeng, Y.L.; Stephens, D.S. Antimicrobial peptide resistance in Neisseria meningitidis. Biochim. Biophys. Acta, 2015, 1848(11 Pt B), 3026-3031.
[] [PMID: 26002321]
Woods, C.R.; Smith, A.L.; Wasilauskas, B.L.; Campos, J.; Givner, L.B. Invasive disease caused by Neisseria meningitidis relatively resistant to penicillin in North Carolina. J. Infect. Dis., 1994, 170(2), 453-456.
[] [PMID: 8035036]
Martinez, I.; Palma, S.; Alonso, R.; Valdés, E.; Llanes, R.; Sosa, J.; Bravo, J. Detection de cepas de Neisseria meningitidis com susceptibilidad intermédia a la penicilin. Enf. Infec. Microb., 1997, 17, 23-26.
Sosa, J.; Llanes, R.; Guzmán, D.; Quintana, I.; Flores, M.; Gutiérrez, O. Typing and susceptibility to penicillin of Neisseria meningitidis isolated from patients in Cuba (1993-1999). Mem. Inst. Oswaldo Cruz, 2001, 96(4), 523-525.
[] [PMID: 11391426]
Latorre, C.; Gene, A.; Juncosa, T.; Munoz, C.; Gonzalez-Cuevas, F. Neisseria meningitidis: evolution of penicillin resistant and pheno-type in a children’s hospital. Acta Paediatr., 2000, 89(6), 661.
Souza, A.L.A.; Díaz-Dellavalle, P.; Cabrera, A.; Larrañaga, P.; Dalla-Rizza, M.; De-Simone, S.G. Antimicrobial activity of pleurocidin is retained in Plc-2, a C-terminal 12-amino acid fragment. Peptides, 2013, 45, 78-84.
[] [PMID: 23603258]
Nicoletti, I.; Migliorati, G.; Pagliacci, M.C.; Grignani, F.; Riccardi, C. A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry. J. Immunol. Methods, 1991, 139(2), 271-279.
[] [PMID: 1710634]
Ásgeirsson, B.; Hartemink, R.; Chlebowski, J.F. Alkaline phosphatase from atlantics cod (Godus morhua). Comp. Biochem. Physiol., 1995, 110B, 315-329.
van ’t Hof, W.; Veerman, E.C.; Helmerhorst, E.J.; Amerongen, A.V. Antimicrobial peptides: properties and applicability. Biol. Chem., 2001, 382(4), 597-619.
[PMID: 11405223]
Steiner, H.; Andreu, D.; Merrifield, R.B. Binding and action of cecropin and cecropin analogues: antibacterial peptides from insects. Biochim. Biophys. Acta, 1988, 939(2), 260-266.
[] [PMID: 3128324]
Silvestro, L.; Weiser, J.N.; Axelsen, P.H. Antibacterial and antimembrane activities of cecropin A in Escherichia coli. Antimicrob. Agents Chemother., 2000, 44(3), 602-607.
[] [PMID: 10681325]
Otvos, L., Jr The short proline-rich antibacterial peptide family. Cell. Mol. Life Sci., 2002, 59(7), 1138-1150.
[] [PMID: 12222961]
Skerlavaj, B.; Romeo, D.; Gennaro, R. Rapid membrane permeabilization and inhibition of vital functions of gram-negative bacteria by bactenecins. Infect. Immun., 1990, 58(11), 3724-3730.
[PMID: 2228243]
Yang, L.; Harroun, T.A.; Weiss, T.M.; Ding, L.; Huang, H.W. Barrel-stave model or toroidal model? A case study on melittin pores. Biophys. J., 2001, 81(3), 1475-1485.
[] [PMID: 11509361]
Herrera, A.I.; Tomich, J.M.; Prakash, O. Membrane interacting peptides: A review. Curr. Protein Pept. Sci., 2016, 17(8), 827-841.
[] [PMID: 27226195]
Sierra, J.M.; Fusté, E.; Rabanal, F.; Vinuesa, T.; Viñas, M. An overview of antimicrobial peptides and the latest advances in their development. Expert Opin. Biol. Ther., 2017, 17(6), 663-676.
[] [PMID: 28368216]
Bechinger, B. Structure and functions of channel-forming peptides: magainins, cecropins, melittin and alamethicin. J. Membr. Biol., 1997, 156(3), 197-211.
[] [PMID: 9096062]
Eriksson, O.S.; Geörg, M.; Sjölinder, H.; Sillard, R.; Lindberg, S.; Langel, U.; Jonsson, A.B. Identification of cell-penetrating peptides that are bactericidal to Neisseria meningitidis and prevent inflammatory responses upon infection. Antimicrob. Agents Chemother., 2013, 57(8), 3704-3712.
[] [PMID: 23689723]
Alvarez-Bravo, J.; Kurata, S.; Natori, S. Novel synthetic antimicrobial peptides effective against methicillin-resistant Staphylococcus aureus. Biochem. J., 1994, 302(Pt 2), 535-538.
[] [PMID: 8093007]
Alvarez-Bravo, J.; Kurata, S.; Natori, S. Mode of action of an antibacterial peptide, KLKLLLLLKLK-NH2. J. Biochem., 1995, 117(6), 1312-1316.
[] [PMID: 7490276]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy