Rapid Intrabacterial Hydrolysis for Activating Antibiotics against Gram-negative Bacteria

05 March 2019, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

Antimicrobial drug resistance demands novel approaches for improving the efficacy of antibiotics, especially against Gram-negative bacteria. Here we report that conjugating a diglycine (GG) to a prodrug of antibiotics drastically accelerates intrabacterial hydrolysis of ester bond for regenerating the antibiotics against E. coli. Specifically, the attachment of GG to chloramphenicol succinate (CLsu) generates a novel conjugate (CLsuGG), which exhibits about an order of magnitude higher inhibitory efficacy than CLsu against E. coli. This work, for the first time, illustrates that dipeptide conjugation modulates intrabacterial hydrolysis for increasing antibiotic efficacy and reducing adverse drug effects.

Keywords

antimicrobial drugs
Intrabacterial esterases

Comments

Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.