Abstract
The red flour beetle Tribolium castaneum is a common insect pest and has been established as a model beetle to study insect development and immunity. This study demonstrates that defensin 1 from T. castaneum displays in vitro and in vivo antimicrobial activity against drug resistant Staphylococcus aureus strains. The minimum inhibitory concentration (MIC) of defensin 1 against 11 reference and clinical staphylococcal isolates was between 16–64 μg/ml. The putative mode of action of the defensin peptide is disruption of the bacterial cell membrane. The antibacterial activity of defensin 1 was attenuated by salt concentrations of 1.56 mM and 25 mM for NaCl and CaCl2 respectively. Treatment of defensin 1 with the reducing agent dithiothreitol (DTT) at concentrations 1.56 to 3.13 mM abolished the antimicrobial activity of the peptide. In the presence of subinhibitory concentrations of antibiotics that also target the bacterial cell envelope such as telavancin and daptomycin, the MIC of the peptide was as low as 1 μg/ml. Moreover, when tested against an S. aureus strain that was defective in D-alanylation of the cell wall, the MIC of the peptide was 0.5 μg/ml. Defensin 1 exhibited no toxicity against human erythrocytes even at 400 μg/ml. The in vivo activity of the peptide was validated in a Caenorhabditis elegans-MRSA liquid infection assay. These results suggest that defensin 1 behaves similarly to other cationic AMPs in its mode of action against S. aureus and that the activity of the peptide can be enhanced in combination with other antibiotics with similar modes of action or with compounds that have the ability to decrease D-alanylation of the bacterial cell wall.
Highlights
Antimicrobial peptides (AMPs) are short peptides less than 50 amino acids that are naturally produced in diverse organisms including plants and metazoans in response to pathogen insult [1]
Among the 65 AMPs only defensin 1 from Tribolium castaneum (Fig 1A), inhibited the growth of MW2 cells and the rest of the AMPs behaved similar to the DMSO control and did not restrict bacterial growth as determined by visual and spectrophotometric observation (S1 Table)
The rising incidence of drug resistance in S. aureus along with the dwindling supply of antibiotics that are effective against these pathogens has led to an interest in AMPs for potential therapeutic applications [1]
Summary
Antimicrobial peptides (AMPs) are short peptides less than 50 amino acids that are naturally produced in diverse organisms including plants and metazoans in response to pathogen insult [1]. AMPs have been underexploited as potential therapeutics in the past, but the rising tide of drug resistance in Staphylococcus aureus and other bacterial pathogens, coupled with the shrinking pool of available drugs for treating these infections, has necessitated the need to develop alternative treatment strategies and therapeutic compounds. Vancomycin is currently used to treat MRSA as an antibiotic of last resort, vancomycin-resistant S. aureus (VRSA) strains have started to emerge, motivating the urgent development of new antibiotics effective against antibiotic-resistant S. aureus. S. aureus causes approximately 10,800 deaths per year in the United States and approximately 50% of these are due to MRSA. These statistics underscore the urgent need for novel anti-infectives effective against S. aureus
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
