AMPs as Antibiotic Alternatives
For decades, antibiotics have been essential for treating infections. Antibiotics have always had health consequences, indiscriminately affecting both good and bad bacteria. Furthermore, over-prescription and misuse of antibiotics has led to the generation of antibiotic-resistant bacteria and the possibility of a post-antibiotic era. Our lab is working to create “guided” versions of Antimicrobial Peptides (AMPs) as alternatives to antibiotics. Read below to find out more about how we are accomplishing this goal.
Killing the pathogen and not the bystanders
The next steps…
But how will guided antimicrobial peptides be delivered to the stomach and colon without being digested? And how will we manage the development of bacteria resistant to our guided antimicrobial peptides?
We now deliver these peptide via engineered probiotics to avoid degradation. We also are working to show that the targeting the virulence factors of pathogens with a peptide derived from the human receptor for that virulence factor will result in an avirulent bacterium which binds neither the guide peptide nor the receptor.
As with antibiotics, antimicrobial peptides usually have a broad range of action, which results in the destruction of the entire microbiome of the target organ (e.g., the gut) rather than the selective elimination of the single pathogenic bacterial species.
By adding the appropriate guide sequence to an antimicrobial peptide, we generate a fusion peptide which specifically kills the targeted pathogen while leaving the commensal bacteria, essential for human health, unharmed. We are able to produce these guided AMPs in E. coli and achieve toxicity levels against the target as high as unmodified peptides while having little or no effect on off-target bacteria.
We have also achieved expression of antimicrobial peptides in plants, and are the first lab to produce these in plants at commercially-relevant levels. Furthermore, the carrier protein used to achieve this high expression does not need to be cleaved from antimicrobial peptide, allowing an expensive processing step to be eliminated for commercial production and also allowing transgenic plants to produce these antimicrobial peptides at high levels.
Ghidey M., Islam S.M.A., Pruett, G., Kearney C.M. 2019. Making plants into cost-effective bioreactors for highly active antimicrobial peptides. New Biotechnology 56:63-70. https://doi.org/10.1016/j.nbt.2019.12.001
Choudhury, A., Islam, S.M.A., Ghidey, M.R., Kearney, C.M. 2020. Repurposing a drug targeting peptide for targeting antimicrobial peptides against Staphylococcus. Biotechnology Letters, 42(2):287-294. doi.org/10.1007/s10529-019-02779-y