Characterization and in vitro Analysis of Probiotic-Derived Peptides Against Multi Drug Resistance Bacterial Infections

Abstract

An inexorable switch from antibiotics has become a major desideratum to overcome antibiotic resistance. Bacteriocin from Lactobacillus casei , a cardinal probiotic was used to design novel antibacterial peptides named as Probiotic Bacteriocin Derived and Modified (PBDM) peptides (PBDM1: YKWFAHLIKGLC and PBDM2: YKWFRHLIKKLC). The loop-shaped 3D structure of peptides was characterized in silico via molecular dynamics simulation as well as biophysically via spectroscopic methods. Thereafter, in vitro results against multidrug resistant bacterial strains and hospital samples demonstrated the strong antimicrobial activity of PBDM peptides. Further, in vivo studies with PBDM peptides showed downright recovery of balb/c mice from Vancomycin Resistant Staphylococcus aureus (VRSA) infection to its healthy condition. Thereafter, in vitro study with human epithelial cells showed no significant cytotoxic effects with high biocompatibility and good hemocompatibility. In conclusion, PBDM peptides displayed significant antibacterial activity against certain drug resistant bacteria which cause infections in human beings. Future analysis are required to unveil its mechanism of action in order to execute it as an alternative to antibiotics.

Antimicrobial and Amyloidogenic Activity of Peptides. Can Antimicrobial Peptides Be Used against SARS-CoV-2?

“…Bacterial peptides are grouped into the bacteriocin class. Among the known AMPs, there are about 6% of them, and the number of bacteriocins is growing rapidly, since new representatives of this class are being developed [ 93 ]. The main systematic feature of the classification of bacterial AMPs is the structure of the cell wall of bacteria producing peptides.…”

Antimicrobial peptides-An alternative candidates to antibiotics against Staphylococcus aureus and its antibiotic-resistant strains

“…Further, in silico, in vitro, and in vivo studies were performed with these peptides. These studies showed that the peptides were effective against MRSA, VRSA, and wild type S. aureus in vitro [15]. Thus, the shorter length forms of AMPs with modified sequences can be derived from other larger peptides displaying good antibacterial activity.…”

“…According to the secondary structures, peptides are divided into four groups named as β-sheets peptides, α-helical peptides, extended peptides and loops containing peptides [137,138]. Further, to understand the 3D-structure of the AMP, the peptide sequence is used for molecular dynamics simulation [4,15]. The MD simulation helps to predict the possible structure of the peptide in the given time period in an artificial environment created in silico.…”

“…Thus, the mechanism of action and activity of AMPs is influenced by amino acids chain length, overall charge of the peptide, structural conformation, amino acid composition, hydrophobicity, and amphipathicity [139]. These mechanisms are studied using different biophysical techniques like circular dichroism, FTIR spectroscopy, NMR, and other techniques and by performing various biological assays like cellular leakage assay, cell dyes, time-course of killing assay, and other assays [4,15,140,141]. Lastly, the toxicity of the AMPs is determined to understand its safety for better treatments using different assays like the MTT assay, hemolytic assay, microscopic analysis, in vivo model study, serum stability, and other relevant toxicity assays [4,15,141,154].…”

“…Antimicrobial peptides (AMPs) are amphipathic and their natural occurrence provides innate immunity via nonspecific and effective defensive activity against invading pathogens. Further, their ability to enter bacteria, mostly soluble in water or aqueous buffer or organic solvent, possibility to modify and their ability to form a secondary structure like beta sheets and helices, has made them a promising candidate alternative to antibiotics [4,14,15]. AMPs showed prominent activity against fungi and bacteria with decreased resistance compared to antibiotics.…”