The phyllosphere-the aerial surfaces of plants, including leavesis a ubiquitous global habitat that harbors diverse bacterial communities. Phyllosphere bacterial communities have the potential to influence plant biogeography and ecosystem function through their influence on the fitness and function of their hosts, but the host attributes that drive community assembly in the phyllosphere are poorly understood. In this study we used high-throughput sequencing to quantify bacterial community structure on the leaves of 57 tree species in a neotropical forest in Panama. We tested for relationships between bacterial communities on tree leaves and the functional traits, taxonomy, and phylogeny of their plant hosts. Bacterial communities on tropical tree leaves were diverse; leaves from individual trees were host to more than 400 bacterial taxa. Bacterial communities in the phyllosphere were dominated by a core microbiome of taxa including Actinobacteria, Alpha-, Beta-, and Gammaproteobacteria, and Sphingobacteria. Host attributes including plant taxonomic identity, phylogeny, growth and mortality rates, wood density, leaf mass per area, and leaf nitrogen and phosphorous concentrations were correlated with bacterial community structure on leaves. The relative abundances of several bacterial taxa were correlated with suites of host plant traits related to major axes of plant trait variation, including the leaf economics spectrum and the wood densitygrowth/mortality tradeoff. These correlations between phyllosphere bacterial diversity and host growth, mortality, and function suggest that incorporating information on plant-microbe associations will improve our ability to understand plant functional biogeography and the drivers of variation in plant and ecosystem function.tropical forests | host-microbe associations | plant microbiome | microbial ecology T he phyllosphere-the aerial surfaces of plants-is an important and ubiquitous habitat for bacteria (1). It is estimated that on a global scale, the phyllosphere spans more than 10 8 km 2 and is home to up to 10 26 bacterial cells (2). Bacteria are also important to their plant hosts. Leaf-associated bacteria represent a widespread and ancient symbiosis (3, 4) that can influence host growth and function in many ways, including the production of growth-promoting nutrients and hormones (5, 6) and protection of hosts against pathogen infection (7,8). Phyllosphere bacteria have the potential to influence plant biogeography and ecosystem function through their influence on plant performance under different environmental conditions (9-11), but the drivers of variation in leaf-associated bacterial biodiversity among host plants are not well understood.The ability to quantify microbial community structure in depth with environmental sequencing technologies has led to an increasing focus not only on the ecology of individual microbial taxa but on the entire genomic content of communities of microbes in different habitats, or "microbiomes" (12). Numerous studies of host-associated mi...

In bacteria, disulfide bonds confer stability on many proteins exported to the cell envelope or beyond. These proteins include numerous bacterial virulence factors. Thus, bacterial enzymes that promote disulfide bond formation represent targets for compounds inhibiting bacterial virulence. Here, we describe a novel target- and cell-based screening methodology for identifying compounds that inhibit the disulfide bond-forming enzymes E. coli DsbB (EcDsbB) or M. tuberculosis VKOR (MtbVKOR). MtbVKOR can replace EcDsbB although the two are not homologues. Initial screening of 51,487 compounds yielded six specifically inhibiting EcDsbB. These compounds share a structural motif and do not inhibit MtbVKOR. A medicinal chemistry approach led us to select related compounds some of which are much more effective DsbB inhibitors than those found in the screen. These compounds inhibit purified DsbB and prevent anaerobic E. coli growth. Furthermore, these compounds inhibit all but one of the DsbBs of nine other gram-negative pathogenic bacteria tested.

Our understanding of mammalian evolution has become microbiome-aware. While emerging research links mammalian biodiversity and the gut microbiome, we lack insight into which microbes potentially impact mammalian evolution. Microbes common to diverse mammalian species may be strong candidates, as their absence in the gut may affect how the microbiome functionally contributes to mammalian physiology to adversely affect fitness. Identifying such conserved gut microbes is thus important to ultimately assessing the microbiome’s potential role in mammalian evolution. To advance their discovery, we developed an approach that identifies ancestrally related groups of microbes that distribute across mammals in a way that indicates their collective conservation. These conserved clades are presumed to have evolved a trait in their ancestor that matters to their distribution across mammals and which has been retained among clade members. We found not only that such clades do exist among mammals but also that they appear to be subject to natural selection and characterize human evolution.

Studies in laboratory animals demonstrate important relationships between environment, host traits, and microbiome composition. However, host-microbiome relationships in natural systems are understudied. Here, we investigate metapopulation-scale microbiome variation in a wild mammalian host, the desert bighorn sheep (Ovis canadensis nelsoni). We sought to identify over-represented microbial clades and understand how landscape variables and host traits influence microbiome composition across the host metapopulation. To address these questions, we performed 16S sequencing on fecal DNA samples from thirty-nine bighorn sheep across seven loosely connected populations in the Mojave Desert and assessed relationships between microbiome composition, environmental variation, geographic distribution, and microsatellite-derived host population structure and heterozygosity. We first used a phylogenetically-informed algorithm to identify bacterial clades conserved across the metapopulation. Members of genus Ruminococcaceae, genus Lachnospiraceae, and family Christensenellaceae R7 group were among the clades over-represented across the metapopulation, consistent with their known roles as rumen symbionts in domestic livestock. Additionally, compositional variation among hosts correlated with individual-level geographic and genetic structure, and with population-level differences in genetic heterozygosity. This study identifies microbiome community variation across a mammalian metapopulation, potentially associated with genetic and geographic population structure. Our results imply that microbiome composition may diverge in accordance with landscape-scale environmental and host population characteristics.

Zebrafish are increasingly used to study how environmental exposures impact vertebrate gut microbes. However, we understand little about which microbial taxa are common to the zebrafish gut across studies and facilities. Here, we define the zebrafish core gut microbiome to resolve microbiota that are both relatively robust to study or facility effects and likely to drive proper microbiome assembly and functioning due to their conservation. To do so, we integrated publicly available gut microbiome 16S gene sequence data from eight studies into a phylogeny and identified monophyletic clades of gut bacteria that are unexpectedly prevalent across individuals. Doing so revealed 585 core clades of bacteria in the zebrafish gut, including clades within Aeromonas, Pseudomonas, Cetobacterium, Shewanella, Chitinibacter, Fluviicola, Flectobacillus, and Paucibacter. We then applied linear regression to discern which of these core clades are sensitive to an array of different environmental exposures. We found that 200 core clades were insensitive to any exposure we assessed, while 134 core clades were sensitive to more than two exposures. Overall, our analysis defines the zebrafish core gut microbiome and its sensitivity to exposure, which helps future studies to assess the robustness of their results and prioritize taxa for empirical assessments of how gut microbiota mediate the effects of exposure on the zebrafish host.