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PloS one
2014;9 (7): e101742.

Characterization of antibacterial and hemolytic activity of synthetic pandinin 2 variants and their inhibition against Mycobacterium tuberculosis.

Alexis Rodríguez, Elba Villegas, Alejandra Montoya-Rosales, Bruno Rivas-Santiago, Gerardo Corzo
Author Information
  1. Alexis Rodríguez: Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca Morelos, México; Centro de Investigación en Biotecnología, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos, México.
  2. Elba Villegas: Centro de Investigación en Biotecnología, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos, México.
  3. Alejandra Montoya-Rosales: Medical Research Unit-Zacatecas, Mexican Institute of Social Security, UIMZ-IMSS, Zacatecas, Mexico.
  4. Bruno Rivas-Santiago: Medical Research Unit-Zacatecas, Mexican Institute of Social Security, UIMZ-IMSS, Zacatecas, Mexico.
  5. Gerardo Corzo: Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca Morelos, México.
PMID: 25019413 DOI: 10.1371/journal.pone.0101742

Abstract

The contention and treatment of Mycobacterium tuberculosis and other bacteria that cause infectious diseases require the use of new type of antibiotics. Pandinin 2 (Pin2) is a scorpion venom antimicrobial peptide highly hemolytic that has a central proline residue. This residue forms a structural "kink" linked to its pore-forming activity towards human erythrocytes. In this work, the residue Pro14 of Pin2 was both substituted and flanked using glycine residues (P14G and P14GPG) based on the low hemolytic activities of antimicrobial peptides with structural motifs Gly and GlyProGly such as magainin 2 and ponericin G1, respectively. The two Pin2 variants showed antimicrobial activity against E. coli, S. aureus, and M. tuberculosis. However, Pin2 [GPG] was less hemolytic (30%) than that of Pin2 [G] variant. In addition, based on the primary structure of Pin2 [G] and Pin2 [GPG], two short peptide variants were designed and chemically synthesized keeping attention to their physicochemical properties such as hydrophobicity and propensity to adopt alpha-helical conformations. The aim to design these two short antimicrobial peptides was to avoid the drawback cost associated to the synthesis of peptides with large sequences. The short Pin2 variants named Pin2 [14] and Pin2 [17] showed antibiotic activity against E. coli and M. tuberculosis. Besides, Pin2 [14] presented only 25% of hemolysis toward human erythrocytes at concentrations as high as 100 µM, while the peptide Pin2 [17] did not show any hemolytic effect at the same concentration. Furthermore, these short antimicrobial peptides had better activity at molar concentrations against multidrug resistance M. tuberculosis than that of the conventional antibiotics ethambutol, isoniazid and rifampicin. Therefore, Pin2 [14] and Pin2 [17] have the potential to be used as an alternative antibiotics and anti-tuberculosis agents with reduced hemolytic effects.

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MeSH Term

Anti-Bacterial Agents
Cell Line
Circular Dichroism
Drug Evaluation, Preclinical
Escherichia coli
Hemolysis
Hemolytic Agents
Humans
Mycobacterium tuberculosis
Peptides
Protein Conformation
Protein Engineering
Regression Analysis
Staphylococcus aureus

Chemicals

Anti-Bacterial Agents
Hemolytic Agents
Peptides
pandinin 2
Journal Article Research Support, Non-U.S. Gov't

Word Cloud

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