Antibacterial peptides (ABPs) have been proposed as potential candidates for alternative antibacterial agents due to the extensive dissemination of antibiotic resistance. However, ABP isolation from natural resources can be tedious without consistent yield. Moreover, many natural ABPs are not developed for clinical application due to potential toxicity to mammalian cells. Therefore, the objective of this study was to develop a potent ABP with minimal toxicity via phage display selection followed by computer-assisted modification. Briefly, a 12-mer phage-displayed peptide library was used to isolate peptides that bound to the cell surface of Pseudomonas aeruginosa with high affinity. The affinity-selected peptide with the highest selection frequency was modified to PAM-5 (KWKWRPLKRKLVLRM) with enhanced antibacterial features by using an online peptide database. Using in vitro microbroth dilution assay, PAM-5 was shown to be active against a panel of Gram-negative bacteria and selected Gram-positive bacteria. Interestingly, the peptide was stable in human plasma by exhibiting a similar bactericidal effect via ex vivo assay. Scanning electron microscopy and SYTOX Green uptake assay revealed that PAM-5 was able to cause membrane disruption and permeabilization of the bacteria. Additionally, the peptide was also able to bind to bacterial DNA as demonstrated by gel retardation assay. In the time-kill assay, PAM-5 was shown to kill the bacteria rapidly in 10 min. More importantly, PAM-5 was non-cytotoxic to Vero cells and non-haemolytic to human erythrocytes at all concentrations tested for the antibacterial assays. Thus, this study showed that the combination of phage display screening and computer-assisted modification could be used to develop potent novel ABPs, and PAM-5 derived from these approaches is worth to be further elucidated for its potential clinical use.
Aim: To evaluate the potential protective effects of mangosteen peel extract against BPA-induced abnormalities on-pregnant mice fetus at implantation stage and offspring at post-parturition. Methodology: Pregnant mice were orally administered with BPA (100mg kg-1 b.wt.) and mangosteen peel extract (200mg kg-1 b.wt.) for 16 days. In order to evaluate the effect of MPE treatment on fetus at implantation stage, the pregnant mice were euthanized at day 18 and the fetus number and morphology were examined. Another group of treated dams, were allowed to undergo parturition for evaluating the of maternal weight, litter size and offspring sex-skewness. Results: Upon feeding Mangosteen peel extract (MPE), the average daily weight gain of dams were not significantly different from the control and BPA treated dams. The fetus derived from BPA treated dams were detected with abnormalities such as under development, haemorrhage and absence of vein, whereas fetus from dam treated with MPE and BPA as well as control were normal. The average litter size of all the treatment groups were not significantly different from the control group. BPA treated mice had lower pups survival up to 6 weeks compared to the groups treated with MPE and control. Test of proportion analysis showed BPA-treated group had significantly higher fraction female ratio. Interpretation: BPA is known as endocrine disruptor causing oxidative stress to female reproductive system, hence mangosteen peel extract contains antioxidant substances that have the potential to ameliorate the adverse effects of BPA exposure on dams during pregnancy and its fetus development.
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