Brandon Jutras

Assistant Professor

BS –  Eastern Illinois University, Molecular and Cellular Function

PhD – University of Kentucky, College of Medicine, Microbiology

Postdoctoral Fellow –Yale University, Howard Hughes Medical Institute, Microbial Science Institute, Department of Molecular, Cellular and Developmental Biology

Program Focus
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.

Projects


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.

PubMed Site

 

CR Savage , BL Jutras, A Bestor , K Tilly , PA Rosa , Y Tourand, PE Stewart , CA Brissette, B Stevenson. 2018. Borrelia burgdorferi SpoVG DNA- and RNA-binding protein modulates physiology of the Lyme disease spirochete. J Bacteriolin press

NM Abraham*, L Liu*, BL Jutras, A Acar, T Yarovinsky, E Sutton, M Heisig, C Jacobs-Wagner, E Fikrig. 2017. A tick antivirulence protein potentiates antibiotics against Staphylococcus aureus. Antimicrob Agents Chemother. 61(7): e001130017.

NM Abraham*, L Liu*, BL Jutras, S Narasimhan, V Gopalakrishnan, JM Ansari, AK Yadav, F Cava, KK Jefferson, C Jacobs-Wagner, E Fikrig. 2017. Anaplasma-mediated manipulation of arthropod microbiota             to promote infection. Proc Natl Acad Sci USA. 114:781790.

BL Jutras*, M Scott*, B Perry, J Biboy, J Gray, W Vollmer, C Jacobs-Wagner. 2016. Lyme disease and relapsing fever Borrelia elongate through discrete zones of PG synthesis that mark sites of division in the next generation. Proc Natl Acad Sci USA 113:91629170.         

BL Jutras, C Jacobs-Wagner. 2015. Bacterial Evolution: What goes around comes around. Current Biology 15:R496498.

S Chou*, M Daugherty*, S Peterson, J Biboy, BL Jutras, L Fritz-Laylin, M Ferrin, B Harding, C Jacobs-Wagner, X Yang, H Malik, W Vollmer, J Mougous. 2015. Transferred interbacterial antagonism genes augment eukaryotic innate immune function. Nature 518:98101.

G Corder, S Doolen, RR Donahue, MK Winter, BL Jutras, Y He, X Hu, DR Storm, ZJ Wang, KE McCarson, BK Taylor. 2013. Acute injury establishes constitutive µ-opioid receptor activity leading to long-term endogenous analgesia and dependence. Science 341:13941399.

BL Jutras, GS Jones, A Verma, NA Brown, AD Antonicello, AM Chenail, B Stevenson. 2013. Post-transcriptional, self-regulation by the Lyme disease bacterium's BpuR DNA/RNA binding protein. J Bacteriol 195:49154923.

BL Jutras, AM Chenail, DW Carroll, MC Miller, H Zhu, A Bowman, B Stevenson. 2013. BpuR, the Lyme Disease Spirochete's PUR Domain Protein: Identification as a transcriptional modulator and characterization of nucleic acid interactions. J Biol Chem 288:2622026234.                                   

A Koenigs, C Hammerschmidt, BL Jutras, D Barthel, C Skerka, D Kugelstadt, R Wallich, B Stevenson, PF Zipfel, P Kraiczy. 2012. BBA70 of Borrelia burgdorferi binds plasminogen supporting a dual role in dissemination and immune evasion. J Biol Chem 288:2522925243.

BL Jutras, AM Chenail, C Rowland, D Carroll, MC Miller, T Bykowski, B Stevenson. 2013. Eubacterial SpoVG homologs constitute a new family of site-specific DNA-binding proteins. PLoS One 8:e66683.

D Brisson, W Zhou, BL Jutras, S Casjens, B Stevenson. 2013. Distribution of Lyme disease spirochete cp32 prophages and natural diversity among their lipoprotein-encoding erp loci. Appl Environ Microbiol 79:41154128.          

BL Jutras, AM Chenail, B Stevenson. 2013. Changes in bacterial growth rate govern expression of the Borrelia burgdorferi OspC and Erp infection-associated surface proteins. J Bacteriol 195:757764.           

AM Chenail *, BL Jutras*, CA Adams*, LH Burns, A Bowman, A Verma, B Stevenson. 2012. Borrelia burgdorferi cp32 BpaB modulates expression of the prophage NucP nuclease and SsbP single-  stranded DNA-binding protein. J Bacteriol 194:4570–4578.

BL Jutras*, A Bowman*, CA Brissette, CA Adams, A Verma, AM Chenail, B Stevenson. 2012. EbfC (YbaB) is a new type of bacterial nucleoid-associated protein, and a global regulator of gene expression in the Lyme disease spirochete. J Bacteriol 194:3395–3406.

BL Jutras, A Verma, CA Adams, CA Brissette, LH Burns, CR Whetstine, A Bowman, AM Chenail, WR Zückert, B Stevenson. 2012. BpaB and EbfC DNA-binding proteins regulate production of the Lyme disease spirochete's infection-associated Erp surface proteins. J Bacteriol 194:778–786.

BL Jutras, A Verma, B Stevenson. 2012. Identification of novel DNA-binding proteins using DNA-affinity chromatography/pull down. Curr Protoc Microbiol 1:U1F.1.      

BL Jutras, Z Liu, CA Brissette. 2010. Simultaneous isolation of Ixodidae and bacterial (Borrelia spp.) genomic DNA. Curr Protoc Microbiol 1:U1E.2.           

LH Burns, CA Adams, SP Riley, BL Jutras, A Bowman, AM Chenail, AE Cooley, LA Haselhorst, AM Moore, K Babb, MG Fried, B Stevenson. 2010. BpaB, a novel protein encoded by the Lyme disease spirochete's cp32 prophages, binds to erp Operator 2 DNA. Nucleic Acids Res 38:5443–5455.

A Seling*, C Siegel*, V Fingerle, BL Jutras, CA Brissette, C Skerka, R Wallich, PF Zipfel, B Stevenson, P Kraiczy. 2010. Functional characterization of Borrelia spielmanii outer surface proteins that interact with distinct members of the human factor H protein family and with plasminogen. Infect and Immun 78:39–48.

  *Co-first author publication

  Co-corresponding author

               

 

 

Brandon Jutras