Antimicrobial activity of Tachyplesin 1 againstBurkholderia pseudomallei: an in vitro and in silico approach

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.

<i>In silico</i> study and bioprospection of the antibacterial and antioxidant effect of the essential oils of <i>Cymbopogon citratus</i> and <i>Zingiber Officinale</i> against bacteria associated with otitis media in children

“…Kolawole et al www.niprdjopat.gov.net; niprdjopat@gmail.com in shorter periods and aids the designing of better therapeutic compounds [26]. Hence, the aim of this study was to determine the antibacterial effects of the essential oils of Zingiber officinale and Cymbopogon citratus on both Gram positive and Gram negative multi-drug resistant bacteria isolated from children with otitis media using in silico and in vitro approaches.…”

METABOLIC PROFILING, IN SILICO DOCKING AND ANTIBACTERIAL POTENTIAL OF PHYTOCONSTITUENTS FROM Phyllanthus muellerianus LEAVES

“…To support in vitro analysis, in silico investigations have been carried out to explain the mechanism of action of the potential antimicrobial compounds. Lee et. al., (2016) and Gupta et.al, (2013) stated that the in silico methods allow drugligand interaction studies to be performed in shorter periods and aids the designing of better therapeutic compounds [6] [7].…”

“…Lee et. al., (2016) and Gupta et.al, (2013) stated that the in silico methods allow drugligand interaction studies to be performed in shorter periods and aids the designing of better therapeutic compounds [6] [7]. The docking program can be used to characterize the binding site, position the ligand into the binding site (orienting) and evaluate the strength of interaction for a specific ligand-receptor complex ("scoring").…”