title: Small Molecule Restores Itaconate Sensitivity in Salmonella enterica: A Potential New Approach to Treating Bacterial Infections.
abstract: In the context of increasing global antibiotic resistance, the need for alternative therapeutic targets is great. Although new antibiotics and resistance inhibitors provide temporary solutions, they are bound to become obsolete. In this work, we propose a new approach, coined "bacterio-modulation" that aims to restore macrophage potency towards bacterial strains that are able to survive in phagolysosomes. One key defense in the macrophage's arsenal is itaconate, an endogenous molecule with antimicrobial activity. Some intracellular pathogens have evolved to produce itaconate-degrading enzymes, which are required for intracellular proliferation and to promote pathogenicity. We herein present the first molecule able to resensitize Salmonella enterica to itaconate.
authors.affiliation: Department of Chemistry, McGill University, Montreal, Quebec, H3A 0B8, Canada.
authors.forename: Fabien
authors.initials: F
authors.lastname: Hammerer
authors.affiliation: Department of Chemistry, McGill University, Montreal, Quebec, H3A 0B8, Canada.
authors.forename: Justin H
authors.initials: JH
authors.lastname: Chang
authors.affiliation: Department of Chemistry, McGill University, Montreal, Quebec, H3A 0B8, Canada.
authors.forename: Dustin
authors.initials: D
authors.lastname: Duncan
authors.affiliation: Department of Chemistry, McGill University, Montreal, Quebec, H3A 0B8, Canada.
authors.forename: Angel
authors.initials: A
authors.lastname: Castañeda Ruiz
authors.affiliation: Department of Chemistry, McGill University, Montreal, Quebec, H3A 0B8, Canada. karine.auclair@mcgill.ca.
authors.forename: Karine
authors.initials: K
authors.lastname: Auclair
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D012480:Salmonella Infections / Q000188:drug therapy* / Q000378:metabolism; D019779:Salmonella enterica / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013386:Succinates / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D054852:Small Molecule Libraries; D013386:Succinates; C005229:itaconic acid
keywords: antibiotics; intracellular pathogen; itaconate degradation; medicinal chemistry; pantothenate