๐ก Antimicrobial resistance (AMR) poses a global health crisis, and researchers at UC Santa Barbara, led by chemistry professor Guillermo Bazan, have discovered a potential solution in the form of a new class of antibiotics derived from conjugated oligoelectrolytes (COEs). Initially developed for energy harvesting from bacteria, the COEs exhibited unexpected antimicrobial properties, forming the basis for a breakthrough in antibiotic development.
๐ Methods:
The research team, including Cystic Fibrosis Foundation Postdoctoral Fellow Alex Moreland and National University of Singapore (NUS) postdoctoral researchers Kaixi Zhang and Jakkarin Limwongyut, investigated the antimicrobial properties of COEs. Multiple studies were conducted, and the compounds were tested against challenging bacteria, such as ๐๐บ๐ค๐ฐ๐ฃ๐ข๐ค๐ต๐ฆ๐ณ๐ช๐ถ๐ฎ ๐ข๐ฃ๐ด๐ค๐ฆ๐ด๐ด๐ถ๐ด (๐๐ข๐ฃ) ๐ข๐ฏ๐ฅ ๐๐ด๐ฆ๐ถ๐ฅ๐ฐ๐ฎ๐ฐ๐ฏ๐ข๐ด ๐ข๐ฆ๐ณ๐ถ๐จ๐ช๐ฏ๐ฐ๐ด๐ข. The team explored the mechanisms of action, efficacy against biofilms, and selectivity for bacterial membranes over mammalian cells.
๐ Key Scientific Findings:
1. Unexpected Antimicrobial Properties : COEs, initially designed for energy harvesting, demonstrated antimicrobial activity against various bacteria. The potential of COEs to serve as a new class of antibiotics was observed
2. Broad-Spectrum Efficacy : COEs exhibited efficacy against challenging microbes, including Mab, known for its antibiotic resistance and ability to form biofilms. The compounds were effective in eradicating Mab in both in-vitro and in-vivo experiments.
3. Mechanisms of Action: COEs targeted the physical and functional integrity of bacterial cell walls. Membrane remodeling induced by COEs inhibited multiple essential functions simultaneously, making resistance development more challenging for bacteria.
4. Anti-Biofilm Activity: A COE compound demonstrated efficacy against ๐๐ด๐ฆ๐ถ๐ฅ๐ฐ๐ฎ๐ฐ๐ฏ๐ข๐ด ๐ข๐ฆ๐ณ๐ถ๐จ๐ช๐ฏ๐ฐ๐ด๐ข, a biofilm-forming antibiotic-resistant bacteria.
The compound killed bacteria in established biofilms and inhibited biofilm formation, presenting a unique dual action.
5. Selectivity for Bacterial Membranes: Structural features of COEs were investigated to drive affinity for bacterial membranes. COEs demonstrated a mechanism of action that was highly selective for bacterial membranes over mammalian cells.
6. Reduced Resistance Development: COEs’ unique mechanism made it 10 to 1000 times more difficult for bacteria to develop resistance compared to conventional antibiotics. The compounds showed promise in addressing the challenge of antibiotic resistance.
๐ The selectivity for bacterial membranes over mammalian cells addresses concerns of toxicity associated with some existing antibiotics.
๐ Implications and Future Directions:
The research provides a proof-of-concept for COEs as a new class of antibiotics. While early findings are promising, further refinement of COE molecules is needed before advancing to clinical trials. Collaborations with institutes globally, including the Cystic Fibrosis Foundation and Walter Reed Army Institute of Research, indicate growing interest and support for the development of COEs as effective and safe antibiotics.
Link to the study : http://tinyurl.com/mr2ekaf8
