Pan-Drug Resistant Acinetobacter baumannii, but Not Other Strains, Are Resistant to the Bee Venom Peptide Melittin

Abstract

Acinetobacter baumannii is a prevalent pathogen in hospital settings with increasing importance in infections associated with biofilm production. Due to a rapid increase in its drug resistance and the failure of commonly available antibiotics to treat A. baumannii infections, this bacterium has become a critical public health issue. For these multi-drug resistant A. baumannii, polymyxin antibiotics are considered the only option for the treatment of severe infections. Concerning, several polymyxin-resistant A. baumannii strains have been isolated over the last few years. This study utilized pan drug-resistant (PDR) strains of A. baumannii isolated in Brazil, along with susceptible (S) and extreme drug-resistant (XDR) strains in order to evaluate the in vitro activity of melittin, an antimicrobial peptide, in comparison to polymyxin and another antibiotic, imipenem. From a broth microdilution method, the determined minimum inhibitory concentration showed that S and XDR strains were susceptible to melittin. In contrast, PDR A. baumannii was resistant to all treatments. Treatment with the peptide was also observed to inhibit biofilm formation of a susceptible strain and appeared to cause permanent membrane damage. A subpopulation of PDR showed membrane damage, however, it was not sufficient to stop bacterial growth, suggesting that alterations involved with antibiotic resistance could also influence melittin resistance. Presumably, mutations in the PDR that have arisen to confer resistance to widely used therapeutics also confer resistance to melittin. Our results demonstrate the potential of melittin to be used in the control of bacterial infections and suggest that antimicrobial peptides can serve as the basis for the development of new treatments.

Antimicrobial Peptide Cec4 Eradicates Multidrug-Resistant Acinetobacter baumannii in vitro and in vivo

“…Previous studies have reported that A. baumannii will develop resistance to melittin-like AMP. 44 Long-term Cec4 treatment resulted in stable downregulation of key genes in the Sec secretion system, suggesting that Cec4 may interact with proteins secreted by the Sec secretion pathway and exert negative effects on bacterial cells ( Figure 7 ). SecA/E/Y gene in the general secretion pathway and TatA gene in the double arginine translocation Tat transporter both showed significant down-regulation.…”

An Update on the Therapeutic Potential of Antimicrobial Peptides against Acinetobacter baumannii Infections

“…Importantly, the injured derma and surrounding tissue, including red blood cells, showed no toxicity. Brazilian clinical studies confirmed melittin activity against most Acinetobacter strains except for one PDR [ 283 ].…”

Peptides with Therapeutic Potential against Acinetobacter baumanii Infections

“…No toxicity was observed on the injured or healthy derma and circulating red blood cells in the examined mice. Recently, a study that evaluated the melittin against Brazilian clinical strains revealed that most strains were susceptible, except for one pan drug-resistant strain [190].…”