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Published on: October 15, 2013
In vitro susceptibility of Burkholderia pseudomallei to antimicrobial peptides
Sakawrat Kanthawong1, Kamran Nazmi, Surasakdi Wongratanacheewin
1Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
Abstract:
Burkholderia pseudomallei, the causative agent of melioidosis, is intrinsically resistant to many antibiotics, resulting in high mortality rates of 19% in Australia and even 50% in Thailand. Antimicrobial peptides (AMPs) possess potent broad-spectrum bactericidal activities and are regarded as promising therapeutic alternatives in the fight against resistant microorganisms. Moreover, these peptides may also affect inflammation, immune activation and wound healing. In this study, the in vitro activities of 10 AMPs, including histatin 5 and histatin variants, human cathelicidin peptide LL-37 and lactoferrin peptides, against 24 isolates of B. pseudomallei were investigated. The results showed that the antibacterial activities of the individual peptides depended on peptide dose and bacterial isolate. Among the 10 peptides tested, LL-37 exhibited the most effective killing activity. The smooth type A lipopolysaccharide (LPS) phenotype B. pseudomallei appeared to be more susceptible than those expressing the smooth type B LPS and the rough type LPS. Four isolates of B. pseudomallei shown to be resistant to ceftazidime and trimethoprim/sulfamethoxazole were also highly susceptible to LL-37. These data indicate that LL-37 possesses antimicrobial activity against all isolates independent of the LPS phenotype and is therefore a promising peptide to combat B. pseudomallei infections.
Insights
Antimicrobial peptides show promise against drug-resistant Burkholderia pseudomallei. The human cathelicidin peptide LL-37 effectively killed all tested B. pseudomallei isolates, including antibiotic-resistant strains.
Area of Science:
- Microbiology
- Infectious Diseases
- Drug Discovery
Background:
- Burkholderia pseudomallei causes melioidosis, a severe infection with high mortality rates.
- Intrinsic antibiotic resistance in B. pseudomallei necessitates novel therapeutic strategies.
- Antimicrobial peptides (AMPs) offer broad-spectrum bactericidal activity and immunomodulatory effects.
Purpose of the Study:
- To evaluate the in vitro antimicrobial activity of 10 AMPs against 24 B. pseudomallei isolates.
- To identify potent AMPs effective against antibiotic-resistant strains of B. pseudomallei.
- To investigate the influence of lipopolysaccharide (LPS) phenotype on bacterial susceptibility to AMPs.
Main Methods:
- In vitro testing of 10 AMPs, including histatin 5, LL-37, and lactoferrin peptides, against 24 B. pseudomallei isolates.
- Determination of peptide dose-dependency and bacterial isolate variability in antimicrobial activity.
- Assessment of susceptibility across different LPS phenotypes (smooth type A, smooth type B, rough type).
Main Results:
- Peptide efficacy varied with dose and bacterial isolate.
- Human cathelicidin peptide LL-37 demonstrated the most potent killing activity.
- B. pseudomallei with smooth type A LPS were more susceptible than those with type B or rough LPS.
- LL-37 effectively inhibited B. pseudomallei isolates resistant to ceftazidime and trimethoprim/sulfamethoxazole.
Conclusions:
- LL-37 exhibits broad-spectrum antimicrobial activity against B. pseudomallei, irrespective of LPS phenotype.
- LL-37 is a promising therapeutic candidate for treating melioidosis, including infections caused by multidrug-resistant strains.
- AMPs represent a viable alternative to conventional antibiotics for combating B. pseudomallei infections.
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