Periodic Reporting for period 1 - PEPTOX (An innovative peptide system for novel drugs targeting microbial Repeats-In-Toxin adhesins)
Période du rapport: 2020-09-01 au 2022-11-30
Despite progress in infection treatment in the last decades, the prevalence and mortality of infections still poses a heavy
burden over humankind. The development of antimicrobial resistance and the rapid mutagenesis of bacteria that leads to
inefficiency of vaccines, play an important role in maintaining infections high level of threat. Even diseases that have plagued
us for centuries, such as cholera, still challenge medical professionals and cause a significant social cost. New therapeutic
approaches that promise a higher success rate are a pressing need. During my ERC-Starting grant PRISM, we discovered a
high similarity between the ice-binding protein we were studying and the RTX adhesin (FrhA) used by the bacteria of cholera
to attach to the human intestine and infect. The peptides we had created to bind to the ice-binding protein also bound to
FrhA and successfully blocked it, suggesting these peptides could help prevent cholera’s infection. By blocking FrhA, these
peptides could also potentially detach already adhered bacteria, effectively removing cholera and curing the disease.
Moreover, FrhA is similar to the RTX adhesin of most gram-negative bacteria, including those in the priority list of the WHO
(E. coli, K. pneumoniae). Hence, when proven to work, the impact of our discovery may be applicable to a wide range of
severe infectious diseases. In this ERC PoC PEPTOX project, we optimised peptide synthesis and characterisation,
and demonstrated binding in an in vitro cellular model. A feasibility study was also performed to
establish viability of peptide therapeutics for gram-negative infections and determine the overall organisation and direction of
a spin-off start-up dedicated to producing new peptide solutions.
burden over humankind. The development of antimicrobial resistance and the rapid mutagenesis of bacteria that leads to
inefficiency of vaccines, play an important role in maintaining infections high level of threat. Even diseases that have plagued
us for centuries, such as cholera, still challenge medical professionals and cause a significant social cost. New therapeutic
approaches that promise a higher success rate are a pressing need. During my ERC-Starting grant PRISM, we discovered a
high similarity between the ice-binding protein we were studying and the RTX adhesin (FrhA) used by the bacteria of cholera
to attach to the human intestine and infect. The peptides we had created to bind to the ice-binding protein also bound to
FrhA and successfully blocked it, suggesting these peptides could help prevent cholera’s infection. By blocking FrhA, these
peptides could also potentially detach already adhered bacteria, effectively removing cholera and curing the disease.
Moreover, FrhA is similar to the RTX adhesin of most gram-negative bacteria, including those in the priority list of the WHO
(E. coli, K. pneumoniae). Hence, when proven to work, the impact of our discovery may be applicable to a wide range of
severe infectious diseases. In this ERC PoC PEPTOX project, we optimised peptide synthesis and characterisation,
and demonstrated binding in an in vitro cellular model. A feasibility study was also performed to
establish viability of peptide therapeutics for gram-negative infections and determine the overall organisation and direction of
a spin-off start-up dedicated to producing new peptide solutions.