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Pan-Drug Resistant Acinetobacter baumannii, but Not Other Strains, Are Resistant to the Bee Venom Peptide Mellitin
Rangel Karyne1, Guilherme Curty Lechuga1,2, André Luis Almeida Souza1
1FIOCRUZ, Center for Technological, Development in Health (CDTS)/National, Institute of Science and Technology for Innovation in Neglected Population Diseases (INCT-IDPN), Rio de Janeiro 21040-900, Brazil.
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.
Insights
Melittin shows potential against drug-resistant Acinetobacter baumannii infections, inhibiting biofilm formation. However, pan drug-resistant strains exhibit resistance, suggesting cross-resistance mechanisms.
Area of Science:
- Microbiology
- Infectious Diseases
- Drug Discovery
Background:
- Acinetobacter baumannii is a critical hospital pathogen with rising multidrug resistance.
- Polymyxins are last-resort treatments, but resistance is emerging.
- Pan drug-resistant (PDR) strains pose a significant public health threat.
Purpose of the Study:
- To evaluate the in vitro efficacy of melittin against susceptible (S), extensively drug-resistant (XDR), and pan drug-resistant (PDR) Acinetobacter baumannii.
- To compare melittin's activity with polymyxin and imipenem.
- To investigate melittin's effect on biofilm formation and bacterial membrane integrity.
Main Methods:
- Broth microdilution method to determine minimum inhibitory concentrations (MICs).
- Testing of melittin, polymyxin, and imipenem against S, XDR, and PDR A. baumannii strains.
- Assessment of biofilm inhibition and membrane damage.
Main Results:
- Melittin demonstrated in vitro activity against S and XDR A. baumannii strains.
- PDR A. baumannii strains were resistant to melittin, polymyxin, and imipenem.
- Melittin inhibited biofilm formation in a susceptible strain and caused membrane damage.
- PDR strains showed some membrane damage but maintained growth, indicating melittin resistance.
Conclusions:
- Melittin shows promise as a therapeutic agent against certain Acinetobacter baumannii infections.
- Antimicrobial peptides like melittin could form the basis for novel treatments.
- Mechanisms of antibiotic resistance in PDR strains may confer cross-resistance to melittin.
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