NOVEL METAL(LOID)-BASED AND PLANT-BASEDANTIBACTERIAL COMPOSITIONS AND USES THEREOFAGAINST BACTERIAL BIOFILMS

Background and Aim : Antibiotic resistance, biofilm, and persistent infection is a challenge inthe healthcare system. Our research group focuses on exploring the efficacy of Metal(loid)-basedantimicrobials (MBAs) towards novel infection control solutions. In this study, we explored MBAsand Plant-Based Antibacterial Compositions (PBCs) to discover novel antibacterial components.Methods : Synergistic antibacterial potentials of MBAs screened systematically in a total of, ۵۷۶۰combinatorial MBAs concentrations, in lab media and infection related simulated wound fluidagainst six WHO concerned bacteria. The silver nitrate (Ag)-potassium tellurite (Te) combinationwas identified as the most effective MBAs. A quite same experiment carried out to identify themost effective PBCs. In a binary screening method, the selected PBCs and PBCs we screened forthe best combination formula. To understand the molecular mechanisms of MBAs and PBCs,especially their synergism state, in a comparative study, we defined the differentially expressedgene profile under MBAs and PBCs alone and in their optimal synergistic combination using theRNA-seq approach. The study was complemented with metabolomics and direct biochemistryassays. We also evaluate the stress effect and toxicity on the animal model system ofCaenorhabditis elegans.Results : The Te and Ag had significantly better biofilm inhibition and biofilm eradication efficacyas well as the most effective anti-biofilm synergism potency against indicator strains and clinicalisolates. The PBCs-PBCs mix not only was more effective than common antibiotics, but alsoprevented bacterial recovery, decreased the risk of future resistance chance, and it was effective atlower concentrations. Our OMICS study showed, all of our selected PBCs utilized the samepathway for their antibacterial effects. They are mostly targeting bacterial cell membrane in theinitial step rather than other mechanisms, which could be part of the explanation as to why theyare not toxic to the eukaryotic cells. MBAs mainly affected four cellular processes including sulfurhomeostasis (mainly), reactive oxygen species (ROS) response by targeting [Fe-S] centres, energypathways, and the bacterial cell membrane. The C. elegans animal model showed co-applicationof MBAs-PBCs has reduced toxicity over the individuals and provides increased their antioxidantproperties to the host.Conclusion : This study is leading towards a novel antimicrobial formulation that is effective inalso preventing and eradication of persistent infection and biofilms.

کلیدواژه ها:

Biofilm ، Metalloid ، Silver nitrate ، Potassium tellurite ، synergism