MAT Gain of Activity Mutation in Helicobacter pylori Is Associated with Resistance to MTAN Transition State Analogues

Helicobacter pylori is found in the gut lining of more than half of the world’s population, causes gastric ulcers, and contributes to stomach cancers. Menaquinone synthesis in H. pylori relies on the rare futalosine pathway, where H. pylori 5′-methylthioadenosine nucleosidase (MTAN) is proposed to p...

Full description

Saved in:
Bibliographic Details
Published in:ACS infectious diseases 2023-04, Vol.9 (4), p.966-978
Main Authors: Feng, Mu, Namanja-Magliano, Hilda, Rajagopalan, Saranathan, Mishra, Tanmay, Ducati, Rodrigo G., Hirsch, Brett M., Kelly, Libusha, Szymczak, Wendy, Fajardo, Jorge Eduardo, Sidoli, Simone, Fiser, Andras, Jacobs, William R., Schramm, Vern L.
Format: Article
Language:English
Subjects:
Helicobacter pylori - genetics
Humans
N-Glycosyl Hydrolases
Purine-Nucleoside Phosphorylase
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Helicobacter pylori is found in the gut lining of more than half of the world’s population, causes gastric ulcers, and contributes to stomach cancers. Menaquinone synthesis in H. pylori relies on the rare futalosine pathway, where H. pylori 5′-methylthioadenosine nucleosidase (MTAN) is proposed to play an essential role. Transition state analogues of MTAN, including BuT-DADMe-ImmA (BTDIA) and MeT-DADMe-ImmA (MTDIA), exhibit bacteriostatic action against numerous diverse clinical isolates of H. pylori with minimum inhibitory concentrations (MIC’s) of
ISSN:2373-8227
2373-8227
DOI:10.1021/acsinfecdis.2c00644