Performance of a biomass adapted to oncological ward wastewater vs. biomass from municipal WWTP on the removal of pharmaceutical molecules.
Hamon P,Moulin P,Ercolei L,Marrot B
The performance of a biomass adapted to Oncological Ward Wastewater (OWW) in a membrane bioreactor (MBR) was compared with that of a municipal WWTP, on the removal of pharmaceutical molecules and more specifically on their overall resistance and purifying ability in the presence of pharmaceutical cocktails. Sorption and biotransformation mechanisms on two antineoplastics, one antibiotic and a painkiller were evaluated. Sludge acclimated to OWW allowed for a 34% increase in the removal rate and in the minimum inhibition concentration. The percentage of the amounts of specific pharmaceutical compounds removed by biotransformation or by sorption were measured. These results are positive, as they show that the observed removal of pharmaceutical molecules by biomass acclimated to OWW can mostly be attributed to developed biotransformation, unlike the biomass from the municipal WWTP for which sorption is sometimes the only removal mechanism. The biotransformation kinetic and the solid-water distribution coefficients in this study show good agreement with literature data, even for much higher pharmaceutical concentrations in OWW.
Large-scale chemical-genetics yields new M. tuberculosis inhibitor classes.
Johnson Eachan O,LaVerriere Emily,Office Emma,Stanley Mary,Meyer Elisabeth,Kawate Tomohiko,Gomez James E,Audette Rebecca E,Bandyopadhyay Nirmalya,Betancourt Natalia,Delano Kayla,Da Silva Israel,Davis Joshua,Gallo Christina,Gardner Michelle,Golas Aaron J,Guinn Kristine M,Kennedy Sofia,Korn Rebecca,McConnell Jennifer A,Moss Caitlin E,Murphy Kenan C,Nietupski Raymond M,Papavinasasundaram Kadamba G,Pinkham Jessica T,Pino Paula A,Proulx Megan K,Ruecker Nadine,Song Naomi,Thompson Matthew,Trujillo Carolina,Wakabayashi Shoko,Wallach Joshua B,Watson Christopher,Ioerger Thomas R,Lander Eric S,Hubbard Brian K,Serrano-Wu Michael H,Ehrt Sabine,Fitzgerald Michael,Rubin Eric J,Sassetti Christopher M,Schnappinger Dirk,Hung Deborah T
New antibiotics are needed to combat rising levels of resistance, with new Mycobacterium tuberculosis (Mtb) drugs having the highest priority. However, conventional whole-cell and biochemical antibiotic screens have failed. Here we develop a strategy termed PROSPECT (primary screening of strains to prioritize expanded chemistry and targets), in which we screen compounds against pools of strains depleted of essential bacterial targets. We engineered strains that target 474 essential Mtb genes and screened pools of 100-150 strains against activity-enriched and unbiased compound libraries, probing more than 8.5 million chemical-genetic interactions. Primary screens identified over tenfold more hits than screening wild-type Mtb alone, with chemical-genetic interactions providing immediate, direct target insights. We identified over 40 compounds that target DNA gyrase, the cell wall, tryptophan, folate biosynthesis and RNA polymerase, as well as inhibitors that target EfpA. Chemical optimization yielded EfpA inhibitors with potent wild-type activity, thus demonstrating the ability of PROSPECT to yield inhibitors against targets that would have eluded conventional drug discovery.