Antimicrobial activity of Tachyplesin 1 againstBurkholderia pseudomallei: an in vitro and in silico approach.
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 againstB. pseudomalleiin 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 100B. pseudomalleiisolates for planktonic cell susceptibility, where LL-37, and PG1, demonstrated 100.0% susceptibility and TP1 demonstrated 83% susceptibility. Since theB. pseudomalleiactivity was reported on LL-37 and PG1, TP1 was selected for further investigation. TP1 inhibitedB. pseudomalleicells at 61.69 μM, and membrane blebbing was observed using scanning electron microscopy. Moreover, TP1 inhibitedB. pseudomalleicell growth, reaching bactericidal endpoint within 2 h post exposure as compared to ceftazidime (CAZ) (8 h). Furthermore, TP1 was shown to suppress the growth ofB. pseudomalleicells 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 ofEscherichia coli, as well as autolysin, pneumolysin, and pneumococcal surface protein A (PspA) ofStreptococcus pneumoniae. Homology modelledB. pseudomalleiPspA 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. pseudomalleiagent.
Department of Medical Microbiology, Faculty of Medicine, University of Malaya , Kuala Lumpur , Malaysia.
Lyn-Fay
LF
Lee
Department of Medical Microbiology, Faculty of Medicine, University of Malaya , Kuala Lumpur , Malaysia.
Vanitha
V
Mariappan
Department of Medical Microbiology, Faculty of Medicine, University of Malaya , Kuala Lumpur , Malaysia.
Kumutha Malar
KM
Vellasamy
Department of Chemistry, Faculty of Science, University of Malaya , Kuala Lumpur , Malaysia.
Vannajan Sanghiran
0000-0002-2911-7726
VS
Lee
Department of Medical Microbiology, Faculty of Medicine, University of Malaya , Kuala Lumpur , Malaysia.
Jamuna
0000-0001-8679-2122
J
Vadivelu
Antimicrobial peptides; Burkholderia pseudomallei; Melioidosis; Molecular docking; Tachyplesin 1