[en] 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.
Dahl, Jan-Ulrik; Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109, USA
Gray, Michael J; Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109, USA
Bazopoulou, Daphne; Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109, USA
Beaufay, François ; Université de Liège - ULiège > Département des sciences de la vie > Centre d'Ingénierie des Protéines (CIP) ; Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109, USA
Lempart, Justine; Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109, USA
Koenigsknecht, Mark J; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, Michigan 48109, USA
Wang, Ying; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, Michigan 48109, USA
Baker, Jason R; Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan 48109, USA
Hasler, William L; Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan 48109, USA
Young, Vincent B; Department of Internal Medicine/Division of Infectious Diseases &Department of Microbiology and Immunology, The University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
Sun, Duxin; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, Michigan 48109, USA
Jakob, Ursula; Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109, USA
Language :
English
Title :
The anti-inflammatory drug mesalamine targets bacterial polyphosphate accumulation.
Publication date :
23 January 2017
Journal title :
Nature Microbiology
eISSN :
2058-5276
Publisher :
Nature Publishing Group, Basingstoke, Hampshire, England
This work was funded by the National Institute of Health grants GM065318 (to U.J.), AI090871 and AI24255 (to V.B.Y.) and by FDA grants HHSF223201000082C and HHSF223201300460A (to D.S.). Clinical samples were collected with help from the Michigan Institute for Clinical & Health Research (MICHR) NIH grant UL1TR000433. J.-U.D. is supported by a postdoctoral fellowship from the Deutsche Forschungsgemeinschaft grant DA1697/1-1.
