Journal Article

The anti-inflammatory drug mesalamine targets bacterial polyphosphate accumulation

Bazopoulou, Daphne, Hasler, William L., Sun, Duxin, Beaufay, Francois, Baker, Jason R., Gray, Michael J., Wang, Ying, Young, Vincent B., Jakob, Ursula, Dahl, Jan-Ulrik, Lempart, Justine, Koenigsknecht, Mark J.

2017

Overview

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. Mesalamine, the gold-standard ulcerative colitis treatment, rapidly decreases polyphosphate levels in bacterial members of the gut microbiome, sensitizing them towards oxidative stress and reducing colonization and persister cell and biofilm formation.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/326/22/1434 / 631/326/2565/2134 / 631/326/46 / Animals / Anti-Inflammatory Agents, Non-Steroidal / Anti-Inflammatory Agents, Non-Steroidal - administration & dosage / Anti-Inflammatory Agents, Non-Steroidal - pharmacology / Anti-Inflammatory Agents, Non-Steroidal - therapeutic use / Applied Microbiology and Biotechnology / Bacteria / Biochemistry, biophysics & molecular biology / Biochimie, biophysique & biologie moléculaire / Biofilms / Biofilms - drug effects / Biomedical and Life Sciences / brief-communication / Cecum / Cecum - microbiology / Cell Biology / Colitis, Ulcerative / Colitis, Ulcerative - drug therapy / Colitis, Ulcerative - microbiology / Colonization / Escherichia coli / Escherichia coli - drug effects / Feces / Feces - microbiology / Gastrointestinal Microbiome / Gastrointestinal Microbiome - drug effects / Genetics / Gram-Negative Bacteria / Gram-Negative Bacteria - drug effects / Gram-Negative Bacteria - genetics / Gram-Negative Bacteria - physiology / Human health sciences / Humans / Immunology / Infectious Diseases / Inflammatory bowel diseases / Intestinal microflora / Life Sciences / Medical Microbiology / Mesalamine / Mesalamine - administration & dosage / Mesalamine - pharmacology / Mesalamine - therapeutic use / Mice / Microbiologie / Microbiology / Microbiology (medical) / Microbiomes / Oxidative Stress / Oxidative Stress - drug effects / Parasitology / Pharmacie, pharmacologie & toxicologie / Pharmacy, pharmacology & toxicology / Polyphosphates / Polyphosphates - metabolism / Sciences de la santé humaine / Sciences du vivant / Ulcerative colitis / Virology