Jenifer Coburn, PhD
Professor, Medicine (Infectious Diseases) and Microbiology & Immunology; Center for Infectious Disease Research
- Center for Infectious Disease Research
- Borrelia Infections
- Spirochaetales Infections
- Tick-Borne Diseases
Research interests focus on pathogenic spirochetes, a group of bacteria that are able to cause persistent, disseminated infections in immunocompetent animals, including humans. We are currently working with Borrelia burgdorferi, which is maintained in a tick-animal cycle in nature. We also work with another pathogenic spirochete, Leptospira interrogans. Leptospires are maintained in infected animals in nature, but can also survive in water and mud. The focus of our work with both Borrelia and Leptospira is to identify and then test the biologic significance of bacterial proteins that help the bacteria bind to mammalian cell surface receptors, to identify the mammalian cell surface receptors recognized by the bacteria, and ultimately the biological and pathologic significance of the bacterial-mammalian receptor interaction.
In the Borrelia work, we have two main projects ongoing in the lab. In one, we are trying to understand the mechanisms behind the requirement for the B. burgdorferi protein, P66, for the bacteria to cause infection in mammals. P66 binds to mammalian cell surface receptors called integrins and serves as a porin in the bacterial outer membrane. We know that the integrin binding function is important for the bacteria to cross endothelial layers and disseminate to different sites in the body. In another Borrelia project, we developed a new experimental model to determine the roles of bacterial adhesive proteins in how the bacteria colonize different tissues in mammals, and how they survive the mammalian defenses in the bloodstream.
Figure 1. This image is an Ixodes scapularis tick. Shown is the nymphal stage of the tick; the scale bar is 1 mm so these ticks are tiny. These ticks are important in transmitting Borrelia burgdorferi to new host animals, and sometimes to humans.
Figure 2: B. burgdorferi producing a red fluorescent protein in a dispersed tick midgut.
In the Leptospira work, we also focus in how the bacteria interact with endothelial cells. In severe cases of leptospirosis, widespread endothelial damage is seen, and this is associated with hemorrhage. L. interrogans binds to an endothelial cell surface receptor called VE-cadherin, which helps the endothelial cells form cell-cell junctions that maintain the integrity of small blood vessels. We are currently determining how the bacteria disrupt cadherin-cadherin interactions, and determining whether the bacterial proteins that bind VE-cadherin are responsible for the endothelial disruption caused by the bacteria. In a second Leptospira project, we are working to identify the bacterial proteins that help the bacteria bind to kidney cells, as the kidneys are where the bacteria reside in a chronically infected animal and from where they are released into the environment.
Figure 3: Leptospira interrogans (red) binding to human endothelial cells. An endothelial cell surface receptor for L. interrogans, VE-cadherin, is stained in green, but the cell-cell junctions are mostly disrupted. The endothelial cell nuclei are stained in blue.
(Lin YP, Tan X, Caine JA, Castellanos M, Chaconas G, Coburn J, Leong JM.) PLoS Pathog. 2020 05;16(5):e1008516 PMID: 32413091 PMCID: PMC7255614 05/16/2020
(Eshghi A, Gaultney RA, England P, Brûlé S, Miras I, Sato H, Coburn J, Bellalou J, Moriarty TJ, Haouz A, Picardeau M.) Cell Microbiol. 2019 02;21(2):e12949 PMID: 30171791 PMCID: PMC7560960 09/02/2018
(Winslow C, Coburn J.) F1000Res. 2019;8 PMID: 31214329 PMCID: PMC6545822 06/20/2019
(Curtis MW, Hahn BL, Zhang K, Li C, Robinson RT, Coburn J.) Infect Immun. 2018 02;86(2) PMID: 29158430 PMCID: PMC5778354 11/22/2017
(Caine JA, Lin YP, Kessler JR, Sato H, Leong JM, Coburn J.) Cell Microbiol. 2017 12;19(12) PMID: 28873507 PMCID: PMC5680108 09/06/2017
(Sato H, Coburn J.) PLoS Negl Trop Dis. 2017 Jul;11(7):e0005830 PMID: 28750011 PMCID: PMC5549773 07/28/2017
(Hahn BL, Padmore LJ, Ristow LC, Curtis MW, Coburn J.) Clin Vaccine Immunol. 2016 08;23(8):725-31 PMID: 27335385 PMCID: PMC4979176 06/24/2016
(Caine JA, Coburn J.) Front Immunol. 2016;7:442 PMID: 27818662 PMCID: PMC5073149 11/08/2016
(Kumar D, Ristow LC, Shi M, Mukherjee P, Caine JA, Lee WY, Kubes P, Coburn J, Chaconas G.) PLoS Pathog. 2015 Dec;11(12):e1005333 PMID: 26684456 PMCID: PMC4686178 12/20/2015
(Lin YP, Bhowmick R, Coburn J, Leong JM.) Cell Microbiol. 2015 Oct;17(10):1464-76 PMID: 25864455 PMCID: PMC4583806 04/14/2015
(Caine JA, Coburn J.) Infect Immun. 2015 Aug;83(8):3184-94 PMID: 26015482 PMCID: PMC4496602 05/28/2015
(Robbins GT, Hahn BL, Evangelista KV, Padmore L, Aranda PS, Coburn J.) PLoS Negl Trop Dis. 2015 Apr;9(4):e0003712 PMID: 25875373 PMCID: PMC4397020 04/16/2015