Education & Certifications

  • MS, Brigham Young University, Microbiology and Molecular Biology (2015)
  • BS, Brigham Young University, Molecular Biology (2014)

All Publications

  • Robust variation in infant gut microbiome assembly across a spectrum of lifestyles. Science (New York, N.Y.) Olm, M. R., Dahan, D., Carter, M. M., Merrill, B. D., Yu, F. B., Jain, S., Meng, X., Tripathi, S., Wastyk, H., Neff, N., Holmes, S., Sonnenburg, E. D., Jha, A. R., Sonnenburg, J. L. 2022; 376 (6598): 1220-1223


    Infant microbiome assembly has been intensely studied in infants from industrialized nations, but little is known about this process in nonindustrialized populations. We deeply sequenced infant stool samples from the Hadza hunter-gatherers of Tanzania and analyzed them in a global meta-analysis. Infant microbiomes develop along lifestyle-associated trajectories, with more than 20% of genomes detected in the Hadza infant gut representing novel species. Industrialized infants-even those who are breastfed-have microbiomes characterized by a paucity of Bifidobacterium infantis and gene cassettes involved in human milk utilization. Strains within lifestyle-associated taxonomic groups are shared between mother-infant dyads, consistent with early life inheritance of lifestyle-shaped microbiomes. The population-specific differences in infant microbiome composition and function underscore the importance of studying microbiomes from people outside of wealthy, industrialized nations.

    View details for DOI 10.1126/science.abj2972

    View details for PubMedID 35679413

  • The CIAMIB: a Large and Metabolically Diverse Collection of Inflammation-Associated Bacteria from the Murine Gut. mBio Wong, E. O., Brownlie, E. J., Ng, K. M., Kathirgamanathan, S., Yu, F. B., Merrill, B. D., Huang, K. C., Martin, A., Tropini, C., Navarre, W. W. 2022: e0294921


    Gut inflammation directly impacts the growth and stability of commensal gut microbes and can lead to long-lasting changes in microbiota composition that can prolong or exacerbate disease states. While mouse models are used extensively to investigate the interplay between microbes and the inflamed state, the paucity of cultured mouse gut microbes has hindered efforts to determine causal relationships. To address this issue, we are assembling the Collection of Inflammation-Associated Mouse Intestinal Bacteria (CIAMIB). The initial release of this collection comprises 41 isolates of 39 unique bacterial species, covering 4 phyla and containing 10 previously uncultivated isolates, including 1 novel family and 7 novel genera. The collection significantly expands the number of available Muribaculaceae, Lachnospiraceae, and Coriobacteriaceae isolates and includes microbes from genera associated with inflammation, such as Prevotella and Klebsiella. We characterized the growth of CIAMIB isolates across a diverse range of nutritional conditions and predicted their metabolic potential and anaerobic fermentation capacity based on the genomes of these isolates. We also provide the first metabolic analysis of species within the genus Adlercreutzia, revealing these representatives to be nitrate-reducing and severely restricted in their ability to grow on carbohydrates. CIAMIB isolates are fully sequenced and available to the scientific community as a powerful tool to study host-microbiota interactions. IMPORTANCE Attempts to explore the role of the microbiota in animal physiology have resulted in large-scale efforts to cultivate the thousands of microbes that are associated with humans. In contrast, relatively few lab mouse-associated bacteria have been isolated, despite the fact that the overwhelming number of studies on the microbiota use laboratory mice that are colonized with microbes that are quite distinct from those in humans. Here, we report the results of a large-scale isolation of bacteria from the intestines of laboratory mice either prone to or suffering from gut inflammation. This collection comprises dozens of novel isolates, many of which represent the only cultured representatives of their genus or species. We report their basic growth characteristics and genomes and are making them widely available to the greater research community.

    View details for DOI 10.1128/mbio.02949-21

    View details for PubMedID 35266814

  • Molecular hallmarks of heterochronic parabiosis at single-cell resolution. Nature Palovics, R., Keller, A., Schaum, N., Tan, W., Fehlmann, T., Borja, M., Kern, F., Bonanno, L., Calcuttawala, K., Webber, J., McGeever, A., Tabula Muris Consortium, Luo, J., Pisco, A. O., Karkanias, J., Neff, N. F., Darmanis, S., Quake, S. R., Wyss-Coray, T., Almanzar, N., Antony, J., Baghel, A. S., Bakerman, I., Bansal, I., Barres, B. A., Beachy, P. A., Berdnik, D., Bilen, B., Brownfield, D., Cain, C., Chan, C. K., Chen, M. B., Clarke, M. F., Conley, S. D., Demers, A., Demir, K., de Morree, A., Divita, T., du Bois, H., Ebadi, H., Espinoza, F. H., Fish, M., Gan, Q., George, B. M., Gillich, A., Gomez-Sjoberg, R., Green, F., Genetiano, G., Gu, X., Gulati, G. S., Hahn, O., Haney, M. S., Hang, Y., Harris, L., He, M., Hosseinzadeh, S., Huang, A., Huang, K. C., Iram, T., Isobe, T., Ives, F., Jones, R. C., Kao, K. S., Karnam, G., Kershner, A. M., Khoury, N., Kim, S. K., Kiss, B. M., Kong, W., Krasnow, M. A., Kumar, M. E., Kuo, C. S., Lam, J., Lee, D. P., Lee, S. E., Lehallier, B., Leventhal, O., Li, G., Li, Q., Liu, L., Lo, A., Lu, W., Lugo-Fagundo, M. F., Manjunath, A., May, A. P., Maynard, A., McKay, M., McNerney, M. W., Merrill, B., Metzger, R. J., Mignardi, M., Min, D., Nabhan, A. N., Ng, K. M., Nguyen, P. K., Noh, J., Nusse, R., Patkar, R., Peng, W. C., Penland, L., Pollard, K., Puccinelli, R., Qi, Z., Rando, T. A., Rulifson, E. J., Segal, J. M., Sikandar, S. S., Sinha, R., Sit, R. V., Sonnenburg, J., Staehli, D., Szade, K., Tan, M., Tato, C., Tellez, K., Torrez Dulgeroff, L. B., Travaglini, K. J., Tropini, C., Tsui, M., Waldburger, L., Wang, B. M., van Weele, L. J., Weinberg, K., Weissman, I. L., Wosczyna, M. N., Wu, S. M., Xiang, J., Xue, S., Yamauchi, K. A., Yang, A. C., Yerra, L. P., Youngyunpipatkul, J., Yu, B., Zanini, F., Zardeneta, M. E., Zee, A., Zhao, C., Zhang, F., Zhang, H., Zhang, M. J., Zhou, L., Zou, J. 2022


    The ability to slow or reverse biological ageing would have major implications for mitigating disease risk and maintaining vitality1. Although an increasing number of interventions show promise for rejuvenation2, their effectiveness on disparate cell types across the body and the molecular pathways susceptible to rejuvenation remain largely unexplored. Here we performed single-cell RNA sequencing on 20 organs to reveal cell-type-specific responses to young and aged blood in heterochronic parabiosis. Adipose mesenchymal stromal cells, haematopoietic stem cells and hepatocytes are among those cell types that are especially responsive. On the pathway level, young blood invokes new gene sets in addition to reversing established ageing patterns, with the global rescue of genes encoding electron transport chain subunits pinpointing a prominent role of mitochondrial function in parabiosis-mediated rejuvenation. We observed an almost universal loss of gene expression with age that is largely mimicked by parabiosis: aged blood reduces global gene expression, and young blood restores it in select cell types. Together, these data lay the groundwork for a systemic understanding of the interplay between blood-borne factors and cellular integrity.

    View details for DOI 10.1038/s41586-022-04461-2

    View details for PubMedID 35236985

  • Independent host- and bacterium-based determinants protect a model symbiosis from phage predation. Cell reports Lynch, J. B., Bennett, B. D., Merrill, B. D., Ruby, E. G., Hryckowian, A. J. 2022; 38 (7): 110376


    Bacteriophages (phages) are diverse and abundant constituents of microbial communities worldwide, capable of modulating bacterial populations in diverse ways. Here, we describe the phage HNL01, which infects the marine bacterium Vibrio fischeri. We use culture-based approaches to demonstrate that mutations in the exopolysaccharide locus of V. fischeri render this bacterium resistant to infection by HNL01, highlighting the extracellular matrix as a key determinant of HNL01 infection. Additionally, using the natural symbiosis between V. fischeri and the squid Euprymna scolopes, we show that, during colonization, V. fischeri is protected from phages present in the ambient seawater. Taken together, these findings shed light on independent yet synergistic host- and bacterium-based strategies for resisting symbiosis-disrupting phage predation, and we present important implications for understanding these strategies in the context of diverse host-associated microbial ecosystems.

    View details for DOI 10.1016/j.celrep.2022.110376

    View details for PubMedID 35172163

  • Community-led, integrated, reproducible multi-omics with anvi'o. Nature microbiology Eren, A. M., Kiefl, E., Shaiber, A., Veseli, I., Miller, S. E., Schechter, M. S., Fink, I., Pan, J. N., Yousef, M., Fogarty, E. C., Trigodet, F., Watson, A. R., Esen, O. C., Moore, R. M., Clayssen, Q., Lee, M. D., Kivenson, V., Graham, E. D., Merrill, B. D., Karkman, A., Blankenberg, D., Eppley, J. M., Sjodin, A., Scott, J. J., Vazquez-Campos, X., McKay, L. J., McDaniel, E. A., Stevens, S. L., Anderson, R. E., Fuessel, J., Fernandez-Guerra, A., Maignien, L., Delmont, T. O., Willis, A. D. 2021; 6 (1): 3–6

    View details for DOI 10.1038/s41564-020-00834-3

    View details for PubMedID 33349678

  • A metabolomics pipeline for the mechanistic interrogation of the gut microbiome. Nature Han, S., Van Treuren, W., Fischer, C. R., Merrill, B. D., DeFelice, B. C., Sanchez, J. M., Higginbottom, S. K., Guthrie, L., Fall, L. A., Dodd, D., Fischbach, M. A., Sonnenburg, J. L. 2021; 595 (7867): 415-420


    Gut microorganisms modulate host phenotypes and are associated with numerous health effects in humans, ranging from host responses to cancer immunotherapy to metabolic disease and obesity. However, difficulty in accurate and high-throughput functional analysis of human gut microorganisms has hindered efforts to define mechanistic connections between individual microbial strains and host phenotypes. One key way in which the gut microbiome influences host physiology is through the production of small molecules1-3, yet progress in elucidating this chemical interplay has been hindered by limited tools calibrated to detect the products of anaerobic biochemistry in the gut. Here we construct a microbiome-focused, integrated mass-spectrometry pipeline to accelerate the identification of microbiota-dependent metabolites in diverse sample types. We report the metabolic profiles of 178 gut microorganism strains using our library of 833 metabolites. Using this metabolomics resource, we establish deviations in the relationships between phylogeny and metabolism, use machine learning to discover a previously undescribed type of metabolism in Bacteroides, and reveal candidate biochemical pathways using comparative genomics. Microbiota-dependent metabolites can be detected in diverse biological fluids from gnotobiotic and conventionally colonized mice and traced back to the corresponding metabolomic profiles of cultured bacteria. Collectively, our microbiome-focused metabolomics pipeline and interactive metabolomics profile explorer are a powerful tool for characterizing microorganisms and interactions between microorganisms and their host.

    View details for DOI 10.1038/s41586-021-03707-9

    View details for PubMedID 34262212

  • Gut-microbiota-targeted diets modulate human immune status. Cell Wastyk, H. C., Fragiadakis, G. K., Perelman, D., Dahan, D., Merrill, B. D., Yu, F. B., Topf, M., Gonzalez, C. G., Van Treuren, W., Han, S., Robinson, J. L., Elias, J. E., Sonnenburg, E. D., Gardner, C. D., Sonnenburg, J. L. 2021


    Diet modulates the gut microbiome, which in turn can impact the immune system. Here, we determined how two microbiota-targeted dietary interventions, plant-based fiber and fermented foods, influence the human microbiome and immune system in healthy adults. Using a 17-week randomized, prospective study (n = 18/arm) combined with -omics measurements of microbiome and host, including extensive immune profiling, we found diet-specific effects. The high-fiber diet increased microbiome-encoded glycan-degrading carbohydrate active enzymes (CAZymes) despite stable microbial community diversity. Although cytokine response score (primary outcome) was unchanged, three distinct immunological trajectories in high-fiber consumers corresponded to baseline microbiota diversity. Alternatively, the high-fermented-food diet steadily increased microbiota diversity and decreased inflammatory markers. The data highlight how coupling dietary interventions to deep and longitudinal immune and microbiome profiling can provide individualized and population-wide insight. Fermented foods may be valuable in countering the decreased microbiome diversity and increased inflammation pervasive in industrialized society.

    View details for DOI 10.1016/j.cell.2021.06.019

    View details for PubMedID 34256014

  • Phase-variable capsular polysaccharides and lipoproteins modify bacteriophage susceptibility in Bacteroides thetaiotaomicron. Nature microbiology Porter, N. T., Hryckowian, A. J., Merrill, B. D., Fuentes, J. J., Gardner, J. O., Glowacki, R. W., Singh, S., Crawford, R. D., Snitkin, E. S., Sonnenburg, J. L., Martens, E. C. 2020


    A variety of cell surface structures dictate interactions between bacteria and their environment, including their viruses (bacteriophages). Members of the human gut Bacteroidetes characteristically produce several phase-variable capsular polysaccharides (CPSs), but their contributions to bacteriophage interactions are unknown. To begin to understand how CPSs have an impact on Bacteroides-phage interactions, we isolated 71 Bacteroides thetaiotaomicron-infecting bacteriophages from two locations in the United States. Using B. thetaiotaomicron strains that express defined subsets of CPSs, we show that CPSs dictate host tropism for these phages and that expression of non-permissive CPS variants is selected under phage predation, enabling survival. In the absence of CPSs, B. thetaiotaomicron escapes bacteriophage predation by altering expression of eight distinct phase-variable lipoproteins. When constitutively expressed, one of these lipoproteins promotes resistance to multiple bacteriophages. Our results reveal important roles for Bacteroides CPSs and other cell surface structures that allow these bacteria to persist under bacteriophage predation, and hold important implications for using bacteriophages therapeutically to target gut symbionts.

    View details for DOI 10.1038/s41564-020-0746-5

    View details for PubMedID 32601452

  • Bacteroides thetaiotaomicron-Infecting Bacteriophage Isolates Inform Sequence-Based Host Range Predictions. Cell host & microbe Hryckowian, A. J., Merrill, B. D., Porter, N. T., Van Treuren, W. n., Nelson, E. J., Garlena, R. A., Russell, D. A., Martens, E. C., Sonnenburg, J. L. 2020


    Our emerging view of the gut microbiome largely focuses on bacteria, while less is known about other microbial components, such as bacteriophages (phages). Though phages are abundant in the gut, very few phages have been isolated from this ecosystem. Here, we report the genomes of 27 phages from the United States and Bangladesh that infect the prevalent human gut bacterium Bacteroides thetaiotaomicron. These phages are mostly distinct from previously sequenced phages with the exception of two, which are crAss-like phages. We compare these isolates to existing human gut metagenomes, revealing similarities to previously inferred phages and additional unexplored phage diversity. Finally, we use host tropisms of these phages to identify alleles of phage structural genes associated with infectivity. This work provides a detailed view of the gut's "viral dark matter" and a framework for future efforts to further integrate isolation- and sequencing-focused efforts to understand gut-resident phages.

    View details for DOI 10.1016/j.chom.2020.06.011

    View details for PubMedID 32652063

  • Ageing hallmarks exhibit organ-specific temporal signatures. Nature Schaum, N. n., Lehallier, B. n., Hahn, O. n., Pálovics, R. n., Hosseinzadeh, S. n., Lee, S. E., Sit, R. n., Lee, D. P., Losada, P. M., Zardeneta, M. E., Fehlmann, T. n., Webber, J. T., McGeever, A. n., Calcuttawala, K. n., Zhang, H. n., Berdnik, D. n., Mathur, V. n., Tan, W. n., Zee, A. n., Tan, M. n., Pisco, A. O., Karkanias, J. n., Neff, N. F., Keller, A. n., Darmanis, S. n., Quake, S. R., Wyss-Coray, T. n. 2020


    Ageing is the single greatest cause of disease and death worldwide, and understanding the associated processes could vastly improve quality of life. Although major categories of ageing damage have been identified-such as altered intercellular communication, loss of proteostasis and eroded mitochondrial function1-these deleterious processes interact with extraordinary complexity within and between organs, and a comprehensive, whole-organism analysis of ageing dynamics has been lacking. Here we performed bulk RNA sequencing of 17 organs and plasma proteomics at 10 ages across the lifespan of Mus musculus, and integrated these findings with data from the accompanying Tabula Muris Senis2-or 'Mouse Ageing Cell Atlas'-which follows on from the original Tabula Muris3. We reveal linear and nonlinear shifts in gene expression during ageing, with the associated genes clustered in consistent trajectory groups with coherent biological functions-including extracellular matrix regulation, unfolded protein binding, mitochondrial function, and inflammatory and immune response. Notably, these gene sets show similar expression across tissues, differing only in the amplitude and the age of onset of expression. Widespread activation of immune cells is especially pronounced, and is first detectable in white adipose depots during middle age. Single-cell RNA sequencing confirms the accumulation of T cells and B cells in adipose tissue-including plasma cells that express immunoglobulin J-which also accrue concurrently across diverse organs. Finally, we show how gene expression shifts in distinct tissues are highly correlated with corresponding protein levels in plasma, thus potentially contributing to the ageing of the systemic circulation. Together, these data demonstrate a similar yet asynchronous inter- and intra-organ progression of ageing, providing a foundation from which to track systemic sources of declining health at old age.

    View details for DOI 10.1038/s41586-020-2499-y

    View details for PubMedID 32669715

  • A single-cell transcriptomic atlas characterizes ageing tissues in the mouse. Nature 2020


    Ageing is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death1. Despite rapid advances over recent years, many of the molecular and cellular processes that underlie the progressive loss of healthy physiology are poorly understood2. To gain a better insight into these processes, here we generate a single-cell transcriptomic atlas across the lifespan of Mus musculus that includes data from 23 tissues and organs. We found cell-specific changes occurring across multiple cell types and organs, as well as age-related changes in the cellular composition of different organs. Using single-cell transcriptomic data, we assessed cell-type-specific manifestations of different hallmarks of ageing-such as senescence3, genomic instability4 and changes in the immune system2. This transcriptomic atlas-which we denote Tabula Muris Senis, or 'Mouse Ageing Cell Atlas'-provides molecular information about how the most important hallmarks of ageing are reflected in a broad range of tissues and cell types.

    View details for DOI 10.1038/s41586-020-2496-1

    View details for PubMedID 32669714

  • Recovery of the Gut Microbiota after Antibiotics Depends on Host Diet, Community Context, and Environmental Reservoirs. Cell host & microbe Ng, K. M., Aranda-Díaz, A. n., Tropini, C. n., Frankel, M. R., Van Treuren, W. n., O'Laughlin, C. T., Merrill, B. D., Yu, F. B., Pruss, K. M., Oliveira, R. A., Higginbottom, S. K., Neff, N. F., Fischbach, M. A., Xavier, K. B., Sonnenburg, J. L., Huang, K. C. 2019; 26 (5): 650–65.e4


    Antibiotics alter microbiota composition and increase infection susceptibility. However, the generalizable effects of antibiotics on and the contribution of environmental variables to gut commensals remain unclear. To address this, we tracked microbiota dynamics with high temporal and taxonomic resolution during antibiotic treatment in a controlled murine system by isolating variables such as diet, treatment history, and housing co-inhabitants. Human microbiotas were remarkably resilient and recovered during antibiotic treatment, with transient dominance of resistant Bacteroides and taxa-asymmetric diversity reduction. In certain cases, in vitro sensitivities were not predictive of in vivo responses, underscoring the significance of host and community context. A fiber-deficient diet exacerbated microbiota collapse and delayed recovery. Species replacement through cross housing after ciprofloxacin treatment established resilience to a second treatment. Single housing drastically disrupted recovery, highlighting the importance of environmental reservoirs. Our findings highlight deterministic microbiota adaptations to perturbations and the translational potential for modulating diet, sanitation, and microbiota composition during antibiotics.

    View details for DOI 10.1016/j.chom.2019.10.011

    View details for PubMedID 31726029

  • Bystander Phage Therapy: Inducing Host-Associated Bacteria to Produce Antimicrobial Toxins against the Pathogen Using Phages. Antibiotics (Basel, Switzerland) Brady, T. S., Fajardo, C. P., Merrill, B. D., Hilton, J. A., Graves, K. A., Eggett, D. L., Hope, S. 2018; 7 (4)


    Brevibacillus laterosporus is often present in beehives, including presence in hives infected with the causative agent of American Foulbrood (AFB), Paenibacillus larvae. In this work, 12 B. laterosporus bacteriophages induced bactericidal products in their host. Results demonstrate that P. larvae is susceptible to antimicrobials induced from field isolates of the bystander, B. laterosporus. Bystander antimicrobial activity was specific against the pathogen and not other bacterial species, indicating that the production was likely due to natural competition between the two bacteria. Three B. laterosporus phages were combined in a cocktail to treat AFB. Healthy hives treated with B. laterosporus phages experienced no difference in brood generation compared to control hives over 8 weeks. Phage presence in bee larvae after treatment rose to 60.8 ± 3.6% and dropped to 0 ± 0.8% after 72 h. In infected hives the recovery rate was 75% when treated, however AFB spores were not susceptible to the antimicrobials as evidenced by recurrence of AFB. We posit that the effectiveness of this treatment is due to the production of the bactericidal products of B. laterosporus when infected with phages resulting in bystander-killing of P. larvae. Bystander phage therapy may provide a new avenue for antibacterial production and treatment of disease.

    View details for PubMedID 30518109

  • A PCR-Based Method for Distinguishing between Two Common Beehive Bacteria, Paenibacillus larvae and Brevibacillus laterosporus APPLIED AND ENVIRONMENTAL MICROBIOLOGY Berg, J. A., Merrill, B. D., Breakwell, D. P., Hope, S., Grose, J. H. 2018; 84 (22)
  • Complete Genome Sequences of 18 Paenibacillus larvae Phages from the Western United States. Microbiology resource announcements Merrill, B. D., Fajardo, C. P., Hilton, J. A., Payne, A. M., Ward, A. T., Walker, J. K., Dhalai, A., Imahara, C., Mangohig, J., Monk, J., Pascacio, C., Rai, P., Salisbury, A., Velez, K., Bloomfield, T. J., Buhler, B., Duncan, S. G., Fuhriman, D. A., George, J., Graves, K., Heaton, K., Hill, H. L., Kim, M., Knabe, B. K., Ririe, D. B., Rogers, S. L., Stamereilers, C., Stephenson, M. B., Usher, B. K., Ward, C. S., Withers, J. M., Wright, C. K., Breakwell, D. P., Grose, J. H., Hope, S., Tsourkas, P. K. 2018; 7 (13)


    We present here the complete genomes of 18 phages that infect Paenibacillus larvae, the causative agent of American foulbrood in honeybees. The phages were isolated between 2014 and 2016 as part of an undergraduate phage discovery course at Brigham Young University. The phages were isolated primarily from bee debris and lysogens.

    View details for PubMedID 30533693



    Paenibacillus larvae and Brevibacillus laterosporus are two bacteria that are members of the Paenibacillaceae family. Both are commonly found in beehives and have historically been difficult to distinguish from each other due to related genetic and phenotypic characteristics and a shared ecological niche. Herein, we discuss the likely mischaracterization of three 16S rRNA sequences previously published as P. larvae and provide the phylogenetic evidence that supported the GenBank re-assignment of the sequences as B. laterosporus We explore the issues that arise by only using 16S rRNA or other single gene analyses to distinguish between these bacteria. We also present three sets of molecular markers, two sets that distinguish P. larvae from B. laterosporus and other closely related species within the Paenibacillus genus, and a third set that distinguishes B. laterosporus from P. larvae and other closely related species within the Brevibacillus genus. These molecular markers provide a tool for proper identification of these oft-mistaken species.Importance 16S rRNA gene sequencing in bacteria has long been held as the gold standard for typing bacteria and, for the most part, is an excellent method of taxonomically identifying different bacterial species. However, the high level of 16S rRNA sequence similarity of some published strains of P. larvae and B. laterosporus, as well as possible horizontal gene transfer events within their shared ecological niche complicates the use of 16S rRNA sequence as an effective molecular marker for differentiating these two species. Additionally, shared characteristics of these bacteria limit the effectiveness of using traditional phenotypic identification assays, such as the catalase test. The results from this study provide PCR methods to quickly differentiate between these two genera and will be useful when studying Brevibacillus, Paenibacillus, and other disease-relevant bacteria commonly found in beehives.

    View details for PubMedID 30217838

  • Complete Genome Sequences of Paenibacillus larvae Phages BN12, Dragolir, Kiel007, Leyra, Likha, Pagassa, PBL1c, and Tadhana. Genome announcements Walker, J. K., Merrill, B. D., Berg, J. A., Dhalai, A., Dingman, D. W., Fajardo, C. P., Graves, K., Hill, H. L., Hilton, J. A., Imahara, C., Knabe, B. K., Mangohig, J., Monk, J., Mun, H., Payne, A. M., Salisbury, A., Stamereilers, C., Velez, K., Ward, A. T., Breakwell, D. P., Grose, J. H., Hope, S., Tsourkas, P. K. 2018; 6 (24)


    We present here the complete genomes of eight phages that infect Paenibacillus larvae, the causative agent of American foulbrood in honeybees. Phage PBL1c was originally isolated in 1984 from a P. larvae lysogen, while the remaining phages were isolated in 2014 from bee debris, honeycomb, and lysogens from three states in the USA.

    View details for PubMedID 29903825

  • Transient Osmotic Perturbation Causes Long-Term Alteration to the Gut Microbiota CELL Tropini, C., Moss, E., Merrill, B., Ng, K., Higginbottom, S., Casavant, E., Gonzalez, C., Fremin, B., Bouley, D., Elias, J., Bhatt, A., Huang, K., Sonnenburg, J. 2018; 173 (7): 1742-+
  • Transient Osmotic Perturbation Causes Long-Term Alteration to the Gut Microbiota. Cell Tropini, C., Moss, E. L., Merrill, B. D., Ng, K. M., Higginbottom, S. K., Casavant, E. P., Gonzalez, C. G., Fremin, B., Bouley, D. M., Elias, J. E., Bhatt, A. S., Huang, K. C., Sonnenburg, J. L. 2018; 173 (7): 1742


    Osmotic diarrhea is a prevalent condition in humans caused by food intolerance, malabsorption, and widespread laxative use. Here, we assess the resilience of the gut ecosystem to osmotic perturbation at multiple length and timescales using mice as model hosts. Osmotic stress caused reproducible extinction of highly abundant taxa and expansion of less prevalent members in human and mouse microbiotas. Quantitative imaging revealed decimation of the mucus barrier during osmotic perturbation, followed by recovery. The immune system exhibited temporary changes in cytokine levels and a lasting IgG response against commensal bacteria. Increased osmolality prevented growth of commensal strains invitro, revealing one mechanism contributing to extinction. Environmental availability of microbiota members mitigated extinction events, demonstrating how species reintroduction can affect community resilience. Our findings (1) demonstrate that even mild osmotic diarrhea can cause lasting changes to the microbiota and host and (2) lay the foundation for interventions that increase system-wide resilience.

    View details for PubMedID 29906449

  • Genome Sequences of 19 Novel Erwinia amylovora Bacteriophages. Genome announcements Esplin, I. N., Berg, J. A., Sharma, R., Allen, R. C., Arens, D. K., Ashcroft, C. R., Bairett, S. R., Beatty, N. J., Bickmore, M., Bloomfield, T. J., Brady, T. S., Bybee, R. N., Carter, J. L., Choi, M. C., Duncan, S., Fajardo, C. P., Foy, B. B., Fuhriman, D. A., Gibby, P. D., Grossarth, S. E., Harbaugh, K., Harris, N., Hilton, J. A., Hurst, E., Hyde, J. R., Ingersoll, K., Jacobson, C. M., James, B. D., Jarvis, T. M., Jaen-Anieves, D., Jensen, G. L., Knabe, B. K., Kruger, J. L., Merrill, B. D., Pape, J. A., Payne Anderson, A. M., Payne, D. E., Peck, M. D., Pollock, S. V., Putnam, M. J., Ransom, E. K., Ririe, D. B., Robinson, D. M., Rogers, S. L., Russell, K. A., Schoenhals, J. E., Shurtleff, C. A., Simister, A. R., Smith, H. G., Stephenson, M. B., Staley, L. A., Stettler, J. M., Stratton, M. L., Tateoka, O. B., Tatlow, P. J., Taylor, A. S., Thompson, S. E., Townsend, M. H., Thurgood, T. L., Usher, B. K., Whitley, K. V., Ward, A. T., Ward, M. E., Webb, C. J., Wienclaw, T. M., Williamson, T. L., Wells, M. J., Wright, C. K., Breakwell, D. P., Hope, S., Grose, J. H. 2017; 5 (46)


    Erwinia amylovora is the causal agent of fire blight, a devastating disease affecting some plants of the Rosaceae family. We isolated bacteriophages from samples collected from infected apple and pear trees along the Wasatch Front in Utah. We announce 19 high-quality complete genome sequences of E.amylovora bacteriophages.

    View details for PubMedID 29146842

  • Bacteriophages as an alternative to conventional antibiotic use for the prevention or treatment of Paenibacillus larvae in honeybee hives JOURNAL OF INVERTEBRATE PATHOLOGY Brady, T., Merrill, B. D., Hilton, J. A., Payne, A. M., Stephenson, M. B., Hope, S. 2017; 150: 94–100


    American Foulbrood (AFB) is an infectious disease caused by the bacteria, Paenibacillus larvae. P. larvae phages were isolated and tested to determine each phages' host range amongst 59 field isolate strains of P. larvae. Three phages were selected to create a phage cocktail for the treatment of AFB infections according to the combined phages' ability to lyse all tested strains of bacteria. Studies were performed to demonstrate the safety and efficacy of the phage cocktail treatment as a replacement for traditional antibiotics for the prevention of AFB and the treatment of active infections. Safety verification studies confirmed that the phage cocktail did not adversely affect the rate of bee death even when administered as an overdose. In a comparative study of healthy hives, traditional prophylactic antibiotic treatment experienced a 38±0.7% decrease in overall hive health, which was statistically lower than hive health observed in control hives. Hives treated with phage cocktail decreased 19±0.8%, which was not statistically different than control hives, which decreased by 10±1.0%. In a study of beehives at-risk for a natural infection, 100±0.5% of phage-treated hives were protected from AFB infection, while 80±0.5% of untreated controls became infected. AFB infected hives began with an average Hitchcock score of 2.25 out of 4 and 100±0.5% of the hives recovered completely within two weeks of treatment with phage cocktail. While the n numbers for the latter two studies are small, the results for both the phage protection rate and the phage cure rate were statistically significant (α=0.05). These studies demonstrate the powerful potential of using a phage cocktail against AFB and establish phage therapy as a feasible treatment.

    View details for PubMedID 28917651

  • DDX6 Represses Aberrant Activation of Interferon-Stimulated Genes. Cell reports Lumb, J. H., Li, Q. n., Popov, L. M., Ding, S. n., Keith, M. T., Merrill, B. D., Greenberg, H. B., Li, J. B., Carette, J. E. 2017; 20 (4): 819–31


    The innate immune system tightly regulates activation of interferon-stimulated genes (ISGs) to avoid inappropriate expression. Pathological ISG activation resulting from aberrant nucleic acid metabolism has been implicated in autoimmune disease; however, the mechanisms governing ISG suppression are unknown. Through a genome-wide genetic screen, we identified DEAD-box helicase 6 (DDX6) as a suppressor of ISGs. Genetic ablation of DDX6 induced global upregulation of ISGs and other immune genes. ISG upregulation proved cell intrinsic, imposing an antiviral state and making cells refractory to divergent families of RNA viruses. Epistatic analysis revealed that ISG activation could not be overcome by deletion of canonical RNA sensors. However, DDX6 deficiency was suppressed by disrupting LSM1, a core component of mRNA degradation machinery, suggesting that dysregulation of RNA processing underlies ISG activation in the DDX6 mutant. DDX6 is distinct among DExD/H helicases that regulate the antiviral response in its singular ability to negatively regulate immunity.

    View details for PubMedID 28746868

    View details for PubMedCentralID PMC5551412

  • A gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites. Nature Dodd, D. n., Spitzer, M. H., Van Treuren, W. n., Merrill, B. D., Hryckowian, A. J., Higginbottom, S. K., Le, A. n., Cowan, T. M., Nolan, G. P., Fischbach, M. A., Sonnenburg, J. L. 2017; 551 (7682): 648–52


    The human gut microbiota produces dozens of metabolites that accumulate in the bloodstream, where they can have systemic effects on the host. Although these small molecules commonly reach concentrations similar to those achieved by pharmaceutical agents, remarkably little is known about the microbial metabolic pathways that produce them. Here we use a combination of genetics and metabolic profiling to characterize a pathway from the gut symbiont Clostridium sporogenes that generates aromatic amino acid metabolites. Our results reveal that this pathway produces twelve compounds, nine of which are known to accumulate in host serum. All three aromatic amino acids (tryptophan, phenylalanine and tyrosine) serve as substrates for the pathway, and it involves branching and alternative reductases for specific intermediates. By genetically manipulating C. sporogenes, we modulate serum levels of these metabolites in gnotobiotic mice, and show that in turn this affects intestinal permeability and systemic immunity. This work has the potential to provide the basis of a systematic effort to engineer the molecular output of the gut bacterial community.

    View details for PubMedID 29168502

  • Software-based analysis of bacteriophage genomes, physical ends, and packaging strategies BMC GENOMICS Merrill, B. D., Ward, A. T., Grose, J. H., Hope, S. 2016; 17


    Phage genome analysis is a rapidly growing field. Recurrent obstacles include software access and usability, as well as genome sequences that vary in sequence orientation and/or start position. Here we describe modifications to the phage comparative genomics software program, Phamerator, provide public access to the code, and include instructions for creating custom Phamerator databases. We further report genomic analysis techniques to determine phage packaging strategies and identification of the physical ends of phage genomes.The original Phamerator code can be successfully modified and custom databases can be generated using the instructions we provide. Results of genome map comparisons within a custom database reveal obstacles in performing the comparisons if a published genome has an incorrect complementarity or an incorrect location of the first base of the genome, which are common issues in GenBank-downloaded sequence files. To address these issues, we review phage packaging strategies and provide results that demonstrate identification of the genome start location and orientation using raw sequencing data and software programs such as PAUSE and Consed to establish the location of the physical ends of the genome. These results include determination of exact direct terminal repeats (DTRs) or cohesive ends, or whether phages may use a headful packaging strategy. Phylogenetic analysis using ClustalO and phamily circles in Phamerator demonstrate that the large terminase gene can be used to identify the phage packaging strategy and thereby aide in identifying the physical ends of the genome.Using available online code, the Phamerator program can be customized and utilized to generate databases with individually selected genomes. These databases can then provide fruitful information in the comparative analysis of phages. Researchers can identify packaging strategies and physical ends of phage genomes using raw data from high-throughput sequencing in conjunction with phylogenetic analyses of large terminase proteins and the use of custom Phamerator databases. We promote publication of phage genomes in an orientation consistent with the physical structure of the phage chromosome and provide guidance for determining this structure.

    View details for DOI 10.1186/s12864-016-3018-2

    View details for Web of Science ID 000384980300001

    View details for PubMedID 27561606

    View details for PubMedCentralID PMC5000459

  • Characterization of Five Novel Brevibacillus Bacteriophages and Genomic Comparison of Brevibacillus Phages PLOS ONE Berg, J. A., Merrill, B. D., Crockett, J. T., Esplin, K. P., Evans, M. R., Heaton, K. E., Hilton, J. A., Hyde, J. R., McBride, M. S., Schouten, J. T., Simister, A. R., Thurgood, T. L., Ward, A. T., Breakwell, D. P., Hope, S., Grose, J. H. 2016; 11 (6)


    Brevibacillus laterosporus is a spore-forming bacterium that causes a secondary infection in beehives following European Foulbrood disease. To better understand the contributions of Brevibacillus bacteriophages to the evolution of their hosts, five novel phages (Jenst, Osiris, Powder, SecTim467, and Sundance) were isolated and characterized. When compared with the five Brevibacillus phages currently in NCBI, these phages were assigned to clusters based on whole genome and proteome synteny. Powder and Osiris, both myoviruses, were assigned to the previously described Jimmer-like cluster. SecTim467 and Jenst, both siphoviruses, formed a novel phage cluster. Sundance, a siphovirus, was assigned as a singleton phage along with the previously isolated singleton, Emery. In addition to characterizing the basic relationships between these phages, several genomic features were observed. A motif repeated throughout phages Jenst and SecTim467 was frequently upstream of genes predicted to function in DNA replication, nucleotide metabolism, and transcription, suggesting transcriptional co-regulation. In addition, paralogous gene pairs that encode a putative transcriptional regulator were identified in four Brevibacillus phages. These paralogs likely evolved to bind different DNA sequences due to variation at amino acid residues predicted to bind specific nucleotides. Finally, a putative transposable element was identified in SecTim467 and Sundance that carries genes homologous to those found in Brevibacillus chromosomes. Remnants of this transposable element were also identified in phage Jenst. These discoveries provide a greater understanding of the diversity of phages, their behavior, and their evolutionary relationships to one another and to their host. In addition, they provide a foundation with which further Brevibacillus phages can be compared.

    View details for DOI 10.1371/journal.pone.0156838

    View details for Web of Science ID 000377824800025

    View details for PubMedID 27304881

    View details for PubMedCentralID PMC4909266

  • Putative type 1 thymidylate synthase and dihydrofolate reductase as signature genes of a novel bastille-like group of phages in the subfamily Spounavirinae BMC GENOMICS Asare, P. T., Jeong, T., Ryu, S., Klumpp, J., Loessner, M. J., Merrill, B. D., Kim, K. 2015; 16


    Spounavirinae viruses have received an increasing interest as tools for the control of harmful bacteria due to their relatively broad host range and strictly virulent phenotype.In this study, we collected and analyzed the complete genome sequences of 61 published phages, either ICTV-classified or candidate members of the Spounavirinae subfamily of the Myoviridae. A set of comparative analyses identified a distinct, recently proposed Bastille-like phage group within the Spounavirinae. More importantly, type 1 thymidylate synthase (TS1) and dihydrofolate reductase (DHFR) genes were shown to be unique for the members of the proposed Bastille-like phage group, and are suitable as molecular markers. We also show that the members of this group encode beta-lactamase and/or sporulation-related SpoIIIE homologs, possibly questioning their suitability as biocontrol agents.We confirm the creation of a new genus--the "Bastille-like group"--in Spounavirinae, and propose that the presence of TS1- and DHFR-encoding genes could serve as signatures for the new Bastille-like group. In addition, the presence of metallo-beta-lactamase and/or SpoIIIE homologs in all members of Bastille-like group phages makes questionable their suitability for use in biocontrol.

    View details for DOI 10.1186/s12864-015-1757-0

    View details for Web of Science ID 000359201700001

    View details for PubMedID 26250905

    View details for PubMedCentralID PMC4528723

  • Genome Sequences of Five Additional Brevibacillus laterosporus Bacteriophages. Genome announcements Merrill, B. D., Berg, J. A., Graves, K. A., Ward, A. T., Hilton, J. A., Wake, B. N., Grose, J. H., Breakwell, D. P., Burnett, S. H. 2015; 3 (5)


    Brevibacillus laterosporus has been isolated from many different environments, including beehives, and produces compounds that are toxic to many organisms. Five B. laterosporus phages have been isolated previously. Here, we announce five additional phages that infect this bacterium, including the first B. laterosporus siphoviruses to be discovered.

    View details for DOI 10.1128/genomeA.01146-15

    View details for PubMedID 26494658

    View details for PubMedCentralID PMC4616168

  • Correction for Sheflo et al., Complete Genome Sequences of Five Brevibacillus laterosporus Bacteriophages. Genome announcements Sheflo, M. A., Gardner, A. V., Merrill, B. D., Fisher, J. N., Lunt, B. L., Breakwell, D. P., Grose, J. H., Burnett, S. H. 2015; 3 (5)

    View details for DOI 10.1128/genomeA.01113-15

    View details for PubMedID 26430035

    View details for PubMedCentralID PMC4591307

  • The Genomes, Proteomes, and Structures of Three Novel Phages That Infect the Bacillus cereus Group and Carry Putative Virulence Factors JOURNAL OF VIROLOGY Grose, J. H., Belnap, D. M., Jensen, J. D., Mathis, A. D., Prince, J. T., Merrill, B. D., Burnett, S. H., Breakwell, D. P. 2014; 88 (20): 11846-11860


    This article reports the results of studying three novel bacteriophages, JL, Shanette, and Basilisk, which infect the pathogen Bacillus cereus and carry genes that may contribute to its pathogenesis. We analyzed host range and superinfection ability, mapped their genomes, and characterized phage structure by mass spectrometry and transmission electron microscopy (TEM). The JL and Shanette genomes were 96% similar and contained 217 open reading frames (ORFs) and 220 ORFs, respectively, while Basilisk has an unrelated genome containing 138 ORFs. Mass spectrometry revealed 23 phage particle proteins for JL and 15 for Basilisk, while only 11 and 4, respectively, were predicted to be present by sequence analysis. Structural protein homology to well-characterized phages suggested that JL and Shanette were members of the family Myoviridae, which was confirmed by TEM. The third phage, Basilisk, was similar only to uncharacterized phages and is an unrelated siphovirus. Cryogenic electron microscopy of this novel phage revealed a T=9 icosahedral capsid structure with the major capsid protein (MCP) likely having the same fold as bacteriophage HK97 MCP despite the lack of sequence similarity. Several putative virulence factors were encoded by these phage genomes, including TerC and TerD involved in tellurium resistance. Host range analysis of all three phages supports genetic transfer of such factors within the B. cereus group, including B. cereus, B. anthracis, and B. thuringiensis. This study provides a basis for understanding these three phages and other related phages as well as their contributions to the pathogenicity of B. cereus group bacteria. Importance: The Bacillus cereus group of bacteria contains several human and plant pathogens, including B. cereus, B. anthracis, and B. thuringiensis. Phages are intimately linked to the evolution of their bacterial hosts and often provide virulence factors, making the study of B. cereus phages important to understanding the evolution of pathogenic strains. Herein we provide the results of detailed study of three novel B. cereus phages, two highly related myoviruses (JL and Shanette) and an unrelated siphovirus (Basilisk). The detailed characterization of host range and superinfection, together with results of genomic, proteomic, and structural analyses, reveal several putative virulence factors as well as the ability of these phages to infect different pathogenic species.

    View details for DOI 10.1128/JVI.01364-14

    View details for Web of Science ID 000342688000020

    View details for PubMedID 25100842

    View details for PubMedCentralID PMC4178739

  • Characterization of Paenibacillus larvae bacteriophages and their genomic relationships to firmicute bacteriophages BMC GENOMICS Merrill, B. D., Grose, J. H., Breakwell, D. P., Burnett, S. H. 2014; 15


    Paenibacillus larvae is a Firmicute bacterium that causes American Foulbrood, a lethal disease in honeybees and is a major source of global agricultural losses. Although P. larvae phages were isolated prior to 2013, no full genome sequences of P. larvae bacteriophages were published or analyzed. This report includes an in-depth analysis of the structure, genomes, and relatedness of P. larvae myoviruses Abouo, Davis, Emery, Jimmer1, Jimmer2, and siphovirus phiIBB_Pl23 to each other and to other known phages.P. larvae phages Abouo, Davies, Emery, Jimmer1, and Jimmer2 are myoviruses with ~50 kbp genomes. The six P. larvae phages form three distinct groups by dotplot analysis. An annotated linear genome map of these six phages displays important identifiable genes and demonstrates the relationship between phages. Sixty phage assembly or structural protein genes and 133 regulatory or other non-structural protein genes were identifiable among the six P. larvae phages. Jimmer1, Jimmer2, and Davies formed stable lysogens resistant to superinfection by genetically similar phages. The correlation between tape measure protein gene length and phage tail length allowed identification of co-isolated phages Emery and Abouo in electron micrographs. A Phamerator database was assembled with the P. larvae phage genomes and 107 genomes of Firmicute-infecting phages, including 71 Bacillus phages. Phamerator identified conserved domains in 1,501 of 6,181 phamilies (only 24.3%) encoded by genes in the database and revealed that P. larvae phage genomes shared at least one phamily with 72 of the 107 other phages. The phamily relationship of large terminase proteins was used to indicate putative DNA packaging strategies. Analyses from CoreGenes, Phamerator, and electron micrograph measurements indicated Jimmer1, Jimmer2, Abouo and Davies were related to phages phiC2, EJ-1, KC5a, and AQ113, which are small-genome myoviruses that infect Streptococcus, Lactobacillus, and Clostridium, respectively.This paper represents the first comparison of phage genomes in the Paenibacillus genus and the first organization of P. larvae phages based on sequence and structure. This analysis provides an important contribution to the field of bacteriophage genomics by serving as a foundation on which to build an understanding of the natural predators of P. larvae.

    View details for DOI 10.1186/1471-2164-15-745

    View details for Web of Science ID 000341790000001

    View details for PubMedID 25174730

    View details for PubMedCentralID PMC4168068

  • Genome Sequences of Three Novel Bacillus cereus Bacteriophages. Genome announcements Grose, J. H., Jensen, J. D., Merrill, B. D., Fisher, J. N., Burnett, S. H., Breakwell, D. P. 2014; 2 (1)


    The Bacillus cereus group is an assemblage of highly related firmicute bacteria that cause a variety of diseases in animals, including insects and humans. We announce three high-quality, complete genome sequences of bacteriophages we isolated from soil samples taken at the bases of fruit trees in Utah County, Utah. While two of the phages (Shanette and JL) are highly related myoviruses, the bacteriophage Basilisk is a siphovirus.

    View details for DOI 10.1128/genomeA.01118-13

    View details for PubMedID 24459255

    View details for PubMedCentralID PMC3900887

  • Genome sequences of five b1 subcluster mycobacteriophages. Genome announcements Breakwell, D. P., Barrus, E. Z., Benedict, A. B., Brighton, A. K., Fisher, J. N., Gardner, A. V., Kartchner, B. J., Ladle, K. C., Lunt, B. L., Merrill, B. D., Morrell, J. D., Burnett, S. H., Grose, J. H. 2013; 1 (6)


    Mycobacteriophages infect members of the Mycobacterium genus in the phylum Actinobacteria and exhibit remarkable diversity. Genome analysis groups the thousands of known mycobacteriophages into clusters, of which the B1 subcluster is currently the third most populous. We report the complete genome sequences of five additional members of the B1 subcluster.

    View details for DOI 10.1128/genomeA.00968-13

    View details for PubMedID 24285667

    View details for PubMedCentralID PMC3869329

  • Complete Genome Sequences of Five Paenibacillus larvae Bacteriophages. Genome announcements Sheflo, M. A., Gardner, A. V., Merrill, B. D., Fisher, J. N., Lunt, B. L., Breakwell, D. P., Grose, J. H., Burnett, S. H. 2013; 1 (6)


    Paenibacillus larvae is a pathogen of honeybees that causes American foulbrood (AFB). We isolated bacteriophages from soil containing bee debris collected near beehives in Utah. We announce five high-quality complete genome sequences, which represent the first completed genome sequences submitted to GenBank for any P. larvae bacteriophage.

    View details for DOI 10.1128/genomeA.00668-13

    View details for PubMedID 24233582

    View details for PubMedCentralID PMC3828306