SUMMARY The selective inhibition of bacterial β-glucuronidases was recently shown to alleviate drug-induced gastrointestinal toxicity in mice, including the damage caused by the widely used anticancer drug irinotecan. Here, we report crystal structures of representative β-glucuronidases from the Firmicutes Streptococcus agalactiae and Clostridium perfringens and the Proteobacterium Escherichia coli, and the characterization of a β-glucuronidase from the Bacteroidetes Bacteroides fragilis. While largely similar in structure, these enzymes exhibit marked differences in catalytic properties and propensities for inhibition, indicating that the microbiome maintains functional diversity in orthologous enzymes. Small changes in the structure of designed inhibitors can induce significant conformational changes in the β-glucuronidase active site. Finally, we establish that β-glucuronidase inhibition does not alter the serum pharmacokinetics of irinotecan or its metabolites in mice. Together, the data presented advance our in vitro and in vivo understanding of the microbial β-glucuronidases, a promising new set of targets for controlling drug-induced gastrointestinal toxicity.

SUMMARYQuantifying the flows generated by the pulsations of jellyfish bells is crucial for understanding the mechanics and efficiency of their swimming and feeding. Recent experimental and theoretical work has focused on the dynamics of vortices in the wakes of swimming jellyfish with relatively simple oral arms and tentacles. The significance of bell pulsations for generating feeding currents through elaborate oral arms and the consequences for particle capture are not as well understood. To isolate the generation of feeding currents from swimming, the pulsing kinematics and fluid flow around the benthic jellyfish Cassiopea spp. were investigated using a combination of videography, digital particle image velocimetry and direct numerical simulation. During the rapid contraction phase of the bell, fluid is pulled into a starting vortex ring that translates through the oral arms with peak velocities that can be of the order of 10cms Supplementary material available online at

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