Modifying Pharmacokinetic Properties of the Gram-Negative Bacteria Targeting Endolysin ML06 Without Affecting Antibacterial Activity.

ABSTRACT: With the rise of antibiotic resistance, there is a need for innovative drugs with alternative mechanisms of action. Endolysins meet most of the requirements, but are limited for parenteral use due to their short blood circulation time. In this article, a number of modifications to the ML06-engineered, lysin-targeting Gram-negative bacteria are proposed to improve its pharmacokinetic parameters. Genetic modification with albumin-binding and dimerization domains ranging from 11-12 aa to 45 aa at both the C- and N-termini has resulted in six enzymes that do not exhibit critically reduced antibacterial properties in vitro, and in the case of the ABP1 modification, an improved antibacterial rate and spectra of enzymes. The ML06-ABP1, ML06-ABP2, and HDD-ML06 modifications also retained activity

SUBMITTER: Antonova NP 

PROVIDER: S-EPMC12072273 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature