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.
Highlights
Antibiotics have saved millions of lives worldwide by significantly decreasing the mortality associated with infectious diseases
Widespread resistance against several types of modern synthetic antibiotics has been discovered among bacterial strains that had been geologically isolated from the surface of the earth for more than 4 millions years [1], demonstrating that mechanisms of antibiotic modification and inactivation are part of the highly specific evolutionary adaptations of these microorganisms to evade the cytotoxic action of antibiotics, even those they have yet to encounter
Infections caused by MDR bacterial strains, resistant to even the latest class of antibiotics, have become a serious and worldwide problem
Summary
Antibiotics have saved millions of lives worldwide by significantly decreasing the mortality associated with infectious diseases. These drugs are losing their effectiveness because of increasing antimicrobial resistance, as their massive and repetitive use in human and veterinary medicine has resulted in the emergence of multidrug-resistant (MDR) strains of bacteria that has become a serious global problem without any signs of abating. In addition to better management of antibiotic use, there is an urgent need for the development of novel therapeutic approaches to treat infections with MDR bacterial strains
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