Synergy Between a Lead Proline-rich Antibacterial Peptide Derivative and Small Molecule Antibiotics
Proline-rich antimicrobial peptides kill bacteria by binding to the C-terminal D-E helix of DnaK, the 70 kDa bacterial heat shock protein and inhibiting chaperone-assisted protein folding . Indeed, the strain selectivity of two family members, drosocin and pyrrhocoricin, and the D-E helix homology of Enterobactericeae can be fully correlated [2,3]. However, mechanistically it is still unclear how binding to the multihelical lid region would allosterically prevent substrate-DnaK interactions taking place 200 residues upstream. If a proper theoretical explanation can be found, the process can be utilized for the development of standalone peptide antibiotics, or for reversing resistance mechanisms that are developed against small molecule antibiotics where failure to kill microorganisms involves the activation of properly folded bacterial proteins, including enzymes. Newly introduced functional enzymes are responsible for the emerging resistance against once powerful...
KeywordsHaemophilus Influenzae Sublethal Dose Peptide Antibiotic Conventional Antibiotic Checkerboard Assay
This work was supported by the Sbarro Health Research Organization.