Abstract
Burkholderia pseudomallei, the causative agent of melioidosis, is intrinsically resistant to many conventional antibiotics. Therefore, alternative antimicrobial agents such as antimicrobial peptides (AMPs) are extensively studied to combat this issue. Our study aims to identify and understand the mode of action of the potential AMP(s) that are effective against B. pseudomallei in both planktonic and biofilm state as well as to predict the possible binding targets on using in vitro and in silico approaches. In the in vitro study, 11 AMPs were tested against 100 B. pseudomallei isolates for planktonic cell susceptibility, where LL-37, and PG1, demonstrated 100.0% susceptibility and TP1 demonstrated 83% susceptibility. Since the B. pseudomallei activity was reported on LL-37 and PG1, TP1 was selected for further investigation. TP1 inhibited B. pseudomallei cells at 61.69 μM, and membrane blebbing was observed using scanning electron microscopy. Moreover, TP1 inhibited B. pseudomallei cell growth, reaching bactericidal endpoint within 2 h post exposure as compared to ceftazidime (CAZ) (8 h). Furthermore, TP1 was shown to suppress the growth of B. pseudomallei cells in biofilm state at concentrations above 221 μM. However, TP1 was cytotoxic to the mammalian cell lines tested. In the in silico study, molecular docking revealed that TP1 demonstrated a strong interaction to the common peptide or inhibitor binding targets for lipopolysaccharide of Escherichia coli, as well as autolysin, pneumolysin, and pneumococcal surface protein A (PspA) of Streptococcus pneumoniae. Homology modelled B. pseudomallei PspA protein (YDP) also showed a favourable binding with a strong electrostatic contribution and nine hydrogen bonds. In conclusion, TP1 demonstrated a good potential as an anti-B. pseudomallei agent.
Highlights
Burkholderia pseudomallei, the causative agent for melioidosis, is commonly found in the soil and water of Southeast Asia, and Northern Australia (Cheng & Currie, 2005)
Among these LL-37, Magainin 2, Tachyplesin 1 (TP1), and protegrin 1 (PG1) were synthesized by SBS Genetech, China; Sushi 1 and Sushi 2 were synthesised by First Base Laboratories, Singapore; Peptide 1037, 1018, and DJK5 were kindly provided by our collaborators from University of British Columbia, Canada; while V2D and ornithine were provided by our collaborators in National University of Singapore (Table 1)
TP1 did not completely inhibit all the tested B. pseudomallei isolates as seen with both LL-37 and PG1, it still was able to inhibit the isolates compared to the remainder eight antimicrobial peptides (AMPs) which did not inhibit the tested isolates
Summary
Burkholderia pseudomallei, the causative agent for melioidosis, is commonly found in the soil and water of Southeast Asia, and Northern Australia (Cheng & Currie, 2005). How to cite this article Lee et al (2016), Antimicrobial activity of Tachyplesin 1 against Burkholderia pseudomallei: an in vitro and in silico approach. B. pseudomallei has been reported to resist the commonly used antibiotics (increased usage of CAZ and amoxicillin/clavulanic acid in treatment), and to the ability to form biofilm in vitro and in vivo (Schweizer, 2012). Incomplete treatment resulted in a high rate of melioidosis relapse. Despite appropriate antimicrobial therapy, mortality from melioidosis septic shock remained high (Wiersinga et al, 2006). There is a need to consider alternative antimicrobial agents, one of which is the antimicrobial peptides (AMPs) (Rotem & Mor, 2009)
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