Aedesin: structure and antimicrobial activity against multidrug resistant bacterial strains

PLoS One. 2014 Aug 27;9(8):e105441. doi: 10.1371/journal.pone.0105441. eCollection 2014.

Abstract

Multidrug resistance, which is acquired by both Gram-positive and Gram-negative bacteria, causes infections that are associated with significant morbidity and mortality in many clinical settings around the world. Because of the rapidly increasing incidence of pathogens that have become resistant to all or nearly all available antibiotics, there is a need for a new generation of antimicrobials with a broad therapeutic range for specific applications against infections. Aedesin is a cecropin-like anti-microbial peptide that was recently isolated from dengue virus-infected salivary glands of the Aedes aegypti mosquito. In the present study, we have refined the analysis of its structural characteristics and have determined its antimicrobial effects against a large panel of multidrug resistant bacterial strains, directly isolated from infected patients. Based the results from nuclear magnetic resonance spectroscopy analysis, Aedesin has a helix-bend-helix structure typical for a member of the family of α-helix anti-microbial peptides. Aedesin efficiently killed Gram-negative bacterial strains that display the most worrisome resistance mechanisms encountered in the clinic, including resistance to carbapenems, aminoglycosides, cephalosporins, 4th generation fluoroquinolones, folate inhibitors and monobactams. In contrast, Gram-positive strains were insensitive to the lytic effects of the peptide. The anti-bacterial activity of Aedesin was found to be salt-resistant, indicating that it is active under physiological conditions encountered in body fluids characterized by ionic salt concentrations. In conclusion, because of its strong lytic activity against multidrug resistant Gram-negative bacterial strains displaying all types of clinically relevant resistance mechanisms known today, Aedesin might be an interesting candidate for the development of alternative treatment for infections caused by these types of bacteria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aedes / chemistry*
  • Aedes / immunology
  • Amino Acid Sequence
  • Animals
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / isolation & purification
  • Anti-Bacterial Agents / pharmacology*
  • Antimicrobial Cationic Peptides / chemical synthesis
  • Antimicrobial Cationic Peptides / chemistry
  • Antimicrobial Cationic Peptides / isolation & purification
  • Antimicrobial Cationic Peptides / pharmacology*
  • Drug Resistance, Multiple, Bacterial / drug effects*
  • Gram-Negative Bacteria / drug effects*
  • Gram-Negative Bacteria / growth & development
  • Insect Proteins / chemical synthesis
  • Insect Proteins / chemistry
  • Insect Proteins / isolation & purification
  • Insect Proteins / pharmacology*
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Structure, Secondary
  • Salivary Glands / chemistry
  • Salivary Glands / immunology
  • Salt Tolerance

Substances

  • Anti-Bacterial Agents
  • Antimicrobial Cationic Peptides
  • Insect Proteins
  • aedesin protein, Aedes aegypti

Grant support

This work was supported by grants from the French Research Agency Agence Nationale de la Recherche (ANR-12-BSV3-0004-01) and the French Infrastructure for Integrated Structural Biology (FRISBI) ANR-10-INSB-05-01. Nadia Leban was supported by a fellowship of the Infectiopôle Sud foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.