title: The anti-inflammatory drug mesalamine targets bacterial polyphosphate accumulation.
abstract: Mesalamine serves as the gold standard in treating ulcerative colitis. However, its precise mechanism(s) of action remains unclear. Here, we show that mesalamine treatment rapidly decreases polyphosphate levels in diverse bacteria, including members of the human gut microbiome. This decrease sensitizes bacteria towards oxidative stress, reduces colonization and attenuates persister cell and biofilm formation, suggesting that mesalamine aids in diminishing the capacity of bacteria to persist within chronically inflamed environments.
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Jan-Ulrik
authors.initials: JU
authors.lastname: Dahl
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Gray
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Daphne
authors.initials: D
authors.lastname: Bazopoulou
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Francois
authors.initials: F
authors.lastname: Beaufay
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Justine
authors.initials: J
authors.lastname: Lempart
authors.affiliation: Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Koenigsknecht
authors.affiliation: Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Jason R
authors.initials: JR
authors.lastname: Baker
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: William L
authors.initials: WL
authors.lastname: Hasler
authors.affiliation: Department of Internal Medicine/Division of Infectious Diseases &Department of Microbiology and Immunology, The University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
authors.forename: Vincent B
authors.initials: VB
authors.lastname: Young
authors.affiliation: Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Duxin
authors.initials: D
authors.lastname: Sun
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Ursula
authors.initials: U
authors.lastname: Jakob
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018441:Biofilms / Q000187:drug effects; D002432:Cecum / Q000382:microbiology; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000382:microbiology; D004926:Escherichia coli / Q000187:drug effects; D005243:Feces / Q000382:microbiology; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D006801:Humans; D019804:Mesalamine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D011122:Polyphosphates / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D011122:Polyphosphates; D019804:Mesalamine