Discovery of Ionophoroantibiotics as a New Antibiotic Class Targeting Metal Homeostasis in Multidrug-Resistant <i>Neisseria gonorrhoeae</i>.

ABSTRACT: The rise of multidrug-resistant (MDR) Neisseria gonorrhoeae is a growing health concern. New treatments are urgently needed as resistance to last-line antibiotics increases. The zinc ionophore, PBT2, has previously been shown to facilitate zinc uptake in bacteria and restore susceptibility to existing antibiotics in combination therapies. In contrast, we demonstrate that PBT2 alone is sufficient to inhibit the growth of N. gonorrhoeae. Guided by this finding, we synthesized a series of 8-hydroxyquinoline-based new chemical entities, herein termed a "ionophoroantibiotics (IP-antibiotics)." These compounds displayed potent activity against MDR N. gonorrhoeae, with several exhibiting greater efficacy than PBT2. Proteomic profiling studies suggested IP-antibiotics disrupt

SUBMITTER: Jen FE 

PROVIDER: S-EPMC12797230 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature