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Bile acids (BAs) mediate the crosstalk between human and microbial cells and influence diseases including Clostridioides difficile infection (CDI). While bile salt hydrolases (BSHs) shape the BA pool by deconjugating conjugated BAs, the basis for their substrate selectivity and impact on C. difficile remain elusive. Here we survey the diversity of BSHs in the gut commensals Lactobacillaceae, which are commonly used as probiotics, and other members of the human gut microbiome. We structurally pinpoint a loop that predicts BSH preferences for either glycine or taurine substrates. BSHs with varying specificities were shown to restrict C. difficile spore germination and growth in vitro and colonization in pre-clinical in vivo models of CDI. Furthermore, BSHs reshape the pool of microbial conjugated bile acids (MCBAs) in the murine gut, and these MCBAs can further restrict C. difficile virulence in vitro. The recognition of conjugated BAs by BSHs defines the resulting BA pool, including the expansive MCBAs. This work provides insights into the structural basis of BSH mechanisms that shape the BA landscape and promote colonization resistance against C. difficile.

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The 4øAr/39Ar technique of K-Ar dating has been used to determine the age of hydrothermal sericite associated with mineralization in the Goonumbla porphyry copper-gold deposits, Lachlan fold belt, New South Wales, Australia. The 4øAr/a9Ar age spectra from Goonumbla hydrothermal sericite indicate that vein and groundmass (potassic and phyllic) alteration were broadly contemporaneous at 439.2 q-1.2 Ma (la). The 4øAr/a9Ar dates obtained from hydrothermal alkali feldspar are considerably younger than those from coeval hydrothermal sericite. U-Pb dating of magmatic zircons by ion microprobe yields an age of 438.5 _ 3.6 Ma (la) for the Nelungaloo Volcanics which underlie the mineralized Goonumbla sequence, providing a maximum age for mineralization and suggesting that the two successions are largely coeval.The 4øAr/39Ar age spectra obtained in this investigation from fine-grained sericite illustrate the amenability of this hydrothermal phase to dating by the 4øAr/3OAr technique and suggest that there is considerable potential for application of this dating method to Phanerozoic ore deposits. The close agreement in ages between the 4øAr/a9Ar and U-Pb results gives confidence in the application of both dating techniques to altered Paleozoic rocks.

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