- BcGSA Advisor
- Research area(s): Molecular and Cellular Biology of Lyme Disease
Ph.D., Microbiology, College of Medicine, University of Kentucky
B.S., Molecular and Cellular Function, Eastern Illinois University
Postdoctoral Fellow –Yale University, Howard Hughes Medical Institute, Microbial Science Institute, Department of Molecular, Cellular and Developmental Biology
Lyme borreliosis is the most reported vector-borne disease in the United States, a disease caused by the spirochetal bacterium Borrelia burgdorferi. Using the essential bacterial cell-wall component peptidoglycan as a bio-tool, in conjunction with quantitative microscopy and molecular techniques, we are discovering new biology that underlies the pathogenesis of Lyme disease. Given that B. burgdorferi is, in many ways, the quintessential member of a poorly understood phylum of bacteria that contains the agents responsible for Syphilis, Relapsing Fever, and Leptospirosis, our findings extend well beyond just Lyme disease, and provide a fundamental framework with direct translational implications for several important human and animal diseases.
1) Cell growth and division
Fundamental to the success of all bacteria is their ability to grow and divide with both precision and speed. Most spirochetes are 10-30 times longer than E. coli, and yet they are able to faithfully self-replicate. One means by which we believe this occurs is through a novel mode of peptidoglycan cell-wall synthesis– a single mother cell is born with a zone of growth at mid-cell that continues throughout the entire cell cycle and becomes the site of cell division. Remarkably, the same mother cell creates new zones at the ¼ and ¾ position along the cell axis that will become sites of cell division in each daughter cell. In essence, mom is deciding the exact site from which each daughter cell will divide! How this occurs in both time and space is entirely unknown, as too are many of the mysteries of spirochete cell wall synthesis, a critical process that is the target of many anti-bacterial therapies. We are currently using novel screens, coupled with new molecular and cellular tools to unravel the remarkable biology that underlies B. burgdorferi growth and division, in addition to many other spirochetes.
2) Pathogenesis of spirochetal peptidoglycan
Peptidoglycan cell-wall can be grossly typed on the basis of chemical composition, with many diodermic bacteria falling into one class and monoderms into the other. Deviations from this dichotomy are rare, and as such many host innate immune sentinel systems are dedicated to the direct detection and distinguishing peptidoglycan chemistry. B. burgdorferi, and likely other spirochetes, have deviated from this dogma and constitute a peptidoglycan type that has not been studied in the context of pathogenesis. How this unique modification influences host cell detection and/or immunomodulation, in addition to vector competence is not known. In a broader sense, the role peptidoglycan plays in Lyme disease is poorly understood, but it seemingly has important connections to Lyme Arthritis.
3) Biophysical properties of peptidoglycan
In most bacteria, peptidoglycan is the major determinant of cell shape. Spirochetes once again deviate from convention – for the most part, their corkscrew morphology is dictated by the machine responsible for locomotion – flagellar filaments that form a ribbon and wrap around the cell cylinder. The seemingly intimate relationship between B. burgdorferi flagellum and peptidoglycan, in addition to how organizational and architectural differences in peptidoglycan contribute to this association, are entirely unknown, but have broad implications on bacterial motility and virulence.
DeHart, T. G., Kushelman, M. R., Hildreth, S. B., Helm, R. F., & Jutras, B. L. (2021). The unusual cell wall of the Lyme disease spirochaete Borrelia burgdorferi is shaped by a tick sugar. Nature Microbiology, 6(12), 1583–1592. https://doi.org/10.1038/s41564-021-01003-w
Bobe, J. R., Jutras, B. L., Horn, L., Embers, M. E., Bailey, A., Moritz, R., Zhang, Y., Soloski, M. J., Ostfeld, R., Marconi, R. T., Aucott, J., Ma'Ayan, A., Keesing, F., Lewis, K., Mamoun, C. B., Rebman, A., McClune, M. E. Breitschwerdt, E. B., Panga, J., Maggi, R., Yang, F., Nemser, B., Ozcan, A., Garner, O., Carlo, D. D., Ballard, Z., Joung, H., Garcia-Romeu, A., Griffiths, R. R., Baumgarth, N. (2021). Recent progress in Lyme disease and remaining challenges. Frontiers in Medicine, 8, 666554 https://doi.org/10.3389/fmed.2021.666554
Brock, A. M., & Jutras, B. L. (2021). A simple method to detect Borrelia burgdorferi sensu lato proteins in different sub-cellular compartments by immunofluorescence. Ticks and tick-borne diseases, 12(6), 101808. https://doi.org/10.1016/j.ttbdis.2021.101808
Davis, M. M., Brock, A. M., DeHart, T. G., Boribong, B. P., Lee, K., McClune, M. E., Chang, Y., Cramer, N., Liu, J., Jones, C. N., & Jutras, B. L. (2021). The peptidoglycan-associated protein NapA plays an important role in the envelope integrity and in the pathogenesis of the Lyme disease spirochete. PLoS pathogens, 17(5), e1009546. https://doi.org/10.1371/journal.ppat.1009546
Zückert, W. R., Jutras, B. L., Toledo, A. M., Bergström, S. (2020). Structure, Function, Biogenesis and Maintenance of the Borrelia Cell Envelope. Current Issues in Molecular Biology. 42, 181-220.
Jutras, B. L.*, Savage, C. R.*, Arnold, W. K., Lethbridge, K. G., Carroll, D. W., Tilly, K., Bestor, A., Zhu, H., Seshu, J., Zückert, W. R., Stewart, P. E., Rosa, P. A., Brissette, C. A., & Stevenson, B. (2019). The Lyme disease spirochete's BpuR DNA/RNA-binding protein is differentially expressed during the mammal-tick infectious cycle, which affects translation of the SodA superoxide dismutase. Molecular microbiology, 112(3), 973–991. https://doi.org/10.1111/mmi.14336.
Jutras, B. L., Lochhead, R. B., Kloos, Z. A., Biboy, J., Strle, K., Booth, C. J., Govers, S. K., Gray, J., Schumann, P., Vollmer, W., Bockenstedt, L. K., Steere, A. C., & Jacobs-Wagner, C. (2019). Borrelia burgdorferi peptidoglycan is a persistent antigen in patients with Lyme arthritis. Proceedings of the National Academy of Sciences of the United States of America, 116(27), 13498–13507. https://doi.org/10.1073/pnas.1904170116
Savage, C. R., Jutras, B. L., Bestor, A., Tilly, K., Rosa, P. A., Tourand, Y., Stewart, P. E., Brissette, C. A., & Stevenson, B. (2018). Borrelia burgdorferi SpoVG DNA- and RNA-Binding Protein Modulates the Physiology of the Lyme Disease Spirochete. Journal of bacteriology, 200(12), e00033-18. https://doi.org/10.1128/JB.00033-18
Abraham, N. M., Liu, L., Jutras, B. L., Murfin, K., Acar, A., Yarovinsky, T. O., Sutton, E., Heisig, M., Jacobs-Wagner, C., & Fikrig, E. (2017). A Tick Antivirulence Protein Potentiates Antibiotics against Staphylococcus aureus. Antimicrobial agents and chemotherapy, 61(7), e00113-17. https://doi.org/10.1128/AAC.00113-17
Abraham, N. M.*, Liu, L.*, Jutras, B. L., Yadav, A. K., Narasimhan, S., Gopalakrishnan, V., Ansari, J. M., Jefferson, K. K., Cava, F., Jacobs-Wagner, C., & Fikrig, E. (2017). Pathogen-mediated manipulation of arthropod microbiota to promote infection. Proceedings of the National Academy of Sciences of the United States of America, 114(5), E781–E790. https://doi.org/10.1073/pnas.1613422114
Jutras, B. L.*, Scott, M.*, Parry, B., Biboy, J., Gray, J., Vollmer, W., & Jacobs-Wagner, C. (2016). Lyme disease and relapsing fever Borrelia elongate through zones of peptidoglycan synthesis that mark division sites of daughter cells. Proceedings of the National Academy of Sciences of the United States of America, 113(33), 9162–9170. https://doi.org/10.1073/pnas.1610805113
Jutras, B. L., & Jacobs-Wagner, C. (2015). Bacterial evolution: what goes around comes around. Current biology : CB, 25(12), R496–R498. https://doi.org/10.1016/j.cub.2015.05.002
Chou, S.*, Daugherty, M. D.*, Peterson, S. B., Biboy, J., Yang, Y., Jutras, B. L., Fritz-Laylin, L. K., Ferrin, M. A., Harding, B. N., Jacobs-Wagner, C., Yang, X. F., Vollmer, W., Malik, H. S., & Mougous, J. D. (2015). Transferred interbacterial antagonism genes augment eukaryotic innate immune function. Nature, 518(7537), 98–101. https://doi.org/10.1038/nature13965
Corder, G., Doolen, S., Donahue, R. R., Winter, M. K., Jutras, B. L., He, Y., Hu, X., Wieskopf, J. S., Mogil, J. S., Storm, D. R., Wang, Z. J., McCarson, K. E., & Taylor, B. K. (2013). Constitutive μ-opioid receptor activity leads to long-term endogenous analgesia and dependence. Science (New York, N.Y.), 341(6152), 1394–1399. https://doi.org/10.1126/science.1239403 §
Jutras, B. L. †, Jones, G. S., Verma, A., Brown, N. A., Antonicello, A. D., Chenail, A. M., & Stevenson, B. (2013). Posttranscriptional self-regulation by the Lyme disease bacterium's BpuR DNA/RNA-binding protein. Journal of bacteriology, 195(21), 4915–4923. https://doi.org/10.1128/JB.00819-13
Koenigs, A., Hammerschmidt, C., Jutras, B. L., Pogoryelov, D., Barthel, D., Skerka, C., Kugelstadt, D., Wallich, R., Stevenson, B., Zipfel, P. F., & Kraiczy, P. (2013). BBA70 of Borrelia burgdorferi is a novel plasminogen-binding protein. The Journal of biological chemistry, 288(35), 25229–25243. https://doi.org/10.1074/jbc.M112.413872
Jutras, B. L., Chenail, A. M., Carroll, D. W., Miller, M. C., Zhu, H., Bowman, A., & Stevenson, B. (2013). Bpur, the Lyme disease spirochete's PUR domain protein: identification as a transcriptional modulator and characterization of nucleic acid interactions. The Journal of biological chemistry, 288(36), 26220–26234. https://doi.org/10.1074/jbc.M113.491357
Jutras, B. L., Chenail, A. M., Rowland, C. L., Carroll, D., Miller, M. C., Bykowski, T., & Stevenson, B. (2013). Eubacterial SpoVG homologs constitute a new family of site-specific DNA-binding proteins. PloS one, 8(6), e66683. https://doi.org/10.1371/journal.pone.0066683
Brisson, D., Zhou, W., Jutras, B. L., Casjens, S., & Stevenson, B. (2013). Distribution of cp32 prophages among Lyme disease-causing spirochetes and natural diversity of their lipoprotein-encoding erp loci. Applied and environmental microbiology, 79(13), 4115–4128. https://doi.org/10.1128/AEM.00817-13
Jutras, B. L., Chenail, A. M., & Stevenson, B. (2013). Changes in bacterial growth rate govern expression of the Borrelia burgdorferi OspC and Erp infection-associated surface proteins. Journal of bacteriology, 195(4), 757–764. https://doi.org/10.1128/JB.01956-12
Chenail, A. M.*, Jutras, B. L.*, Adams, C. A.*, Burns, L. H., Bowman, A., Verma, A., & Stevenson, B. (2012). Borrelia burgdorferi cp32 BpaB modulates expression of the prophage NucP nuclease and SsbP single-stranded DNA-binding protein. Journal of bacteriology, 194(17), 4570–4578. https://doi.org/10.1128/JB.00661-12
Jutras, B. L.*, Bowman, A.*, Brissette, C. A., Adams, C. A., Verma, A., Chenail, A. M., & Stevenson, B. (2012). EbfC (YbaB) is a new type of bacterial nucleoid-associated protein and a global regulator of gene expression in the Lyme disease spirochete. Journal of bacteriology, 194(13), 3395–3406. https://doi.org/10.1128/JB.00252-12
Jutras, B. L., Verma, A., & Stevenson, B. (2012). Identification of novel DNA-binding proteins using DNA-affinity chromatography/pull down. Current protocols in microbiology, Chapter 1, Unit1F.1. https://doi.org/10.1002/9780471729259.mc01f01s24
Jutras, B. L., Verma, A., Adams, C. A., Brissette, C. A., Burns, L. H., Whetstine, C. R., Bowman, A., Chenail, A. M., Zückert, W. R., & Stevenson, B. (2012). BpaB and EbfC DNA-binding proteins regulate production of the Lyme disease spirochete's infection-associated Erp surface proteins. Journal of bacteriology, 194(4), 778–786. https://doi.org/10.1128/JB.06394-11
Jutras, B. L., Liu, Z., & Brissette, C. A. (2010). Simultaneous isolation of Ixodidae and bacterial (Borrelia spp.) genomic DNA. Current protocols in microbiology, Chapter 1, Unit1E.2. https://doi.org/10.1002/9780471729259.mc01e02s19
Burns, L. H., Adams, C. A., Riley, S. P., Jutras, B. L., Bowman, A., Chenail, A. M., Cooley, A. E., Haselhorst, L. A., Moore, A. M., Babb, K., Fried, M. G., & Stevenson, B. (2010). BpaB, a novel protein encoded by the Lyme disease spirochete's cp32 prophages, binds to erp Operator 2 DNA. Nucleic acids research, 38(16), 5443–5455. https://doi.org/10.1093/nar/gkq284
Seling, A., Siegel, C., Fingerle, V., Jutras, B. L., Brissette, C. A., Skerka, C., Wallich, R., Zipfel, P. F., Stevenson, B., & Kraiczy, P. (2010). Functional characterization of Borrelia spielmanii outer surface proteins that interact with distinct members of the human factor H protein family and with plasminogen. Infection and immunity, 78(1), 39–48. https://doi.org/10.1128/IAI.00691-09
*Co-first author publication
§Selected for journal cover