Natural compounds target the M23B zinc metallopeptidase Mpg to modulate <i>Neisseria gonorrhoeae</i> Type IV pilus expression.

ABSTRACT: Neisseria gonorrhoeae uses the Type IV pilus (T4p) to colonize several sites within humans by adhering to host cells and tissues. Previously, we identified a periplasmic M23B zinc metallopeptidase, Mpg, that is necessary to protect from oxidative and nonoxidative killing and these phenotypes are mediated by Mpg activities on T4p expression. Here, we use a high-throughput, target-based screening approach to identify novel inhibitors of Mpg's enzymatic activity. We identified two natural compounds, punicalagin and chebulinic acid, which inhibit the peptidoglycan-hydrolyzing activity of Mpg in a dose-dependent manner. Moreover, treatment of N. gonorrhoeae with these compounds leads to a concomitant decrease in the number of T4p, similar to an mpg mutant. However, these co

SUBMITTER: Nicholson KR 

PROVIDER: S-EPMC11980366 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature