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Mark Wooten, Ph.D.

Media Release:

Dr. Wooten's laboratory is interested in the host/pathogen interactions that lead to the development of two different infectious diseases: Lyme disease and melioidosis.

Lyme diseaseÌý(i.e. Lyme borreliosis) is a particularly interesting and complicated malady that involves two major events: 1) persistent infection of the host by the spirochetal bacteriumÌýBorrelia burgdorferiÌýand 2) the response of the host's innate immune defenses to the organism, which produces the inflammation that leads to the symptoms of Lyme disease while attempting to clear the persistent infection.ÌýB. burgdorferiÌýis a highly infectious tick-borne bacterial obligate parasite that is especially adept at evading host defenses, disseminating widely via spirochetal motility through dense tissues, and persisting long-term within almost any tissue of the body. The infected host mounts a vigorous immune response to these spirochetes, as evidenced by the production of inflammatory soluble mediators and large quantities ofÌýB. burgdorferi-specific antibodies. Although passive transfer ofÌýB. burgdorferi-specific antiserum can prevent naive mice from subsequent infection, the immune response elicited during natural infection is usually unable to clear the infection, resulting in a persisting bacterial reservoir that can re-emerge under various conditions. This persistence in target tissues promotes prolonged stimulation of the host's innate defenses via interaction with endogenous bacterial lipoproteins, resulting in activation of immune pathways that appear to mediate much of the inflammatory pathology indicative of Lyme disease. Based on these dynamics, we are interested in utilizing the well-established murine model of Lyme disease to address the following areas:

• Identification of host immune cell types and mediators that are important in controlling the abilities ofÌýB. burgdorferiÌýto infect, invade, and persist in mammalian host tissues.
• Identification of host signaling pathways that modulate the inflammatory pathology that is characteristic for Lyme disease.
• Usage of intravital microscopy techniques that allow direct visualization of the interactions betweenÌýB. burgdorferiÌýand different immune cell populations within the intact skin of living, infected mice over time.
• Assessment of the importance ofÌýB. burgdorferiÌýmotility and chemotaxis mechanisms for establishing acute and persistent infection in vertebrate and invertebrate hosts.
• Using our findings from the above experiments to identify targets for vaccines or other therapies that restore effective immune clearance.

MelioidosisÌýis a human and animal disease that is caused by infection withÌýBurkholderia pseudomallei, which is endemic within different tropical and subtropical regions worldwide. Acute disease can lead to fulminant septicemia with mortality rates of 40-90%, even with vigorous antibiotic and supportive therapy. Chronic disease can also develop, with recrudescence occurring months to years after initial exposure. While there are some predisposing factors that make certain human populations more susceptible to developing this disease (e.g. diabetes, alcohol abuse, renal disease, etc.), exposure toÌýB. pseudomallei-containing aerosols is reported to have an LD₅₀Ìý≤100 organisms in mice. Based on these properties, B. pseudomallei is considered a Tier 1 select agent with the highest potential for misuse as a biological weapon. This organism is also quite resistant to many classes of antibiotics and there is currently no vaccine. Thus, there is great interest in identifying targets for preventative and/or curative treatments for these infections.

Persistence within innate immune and other cell types appears to be central to the development of melioidosis, providing them with an environment where they can proliferate and spread cell-to-cell via actin polymerization, thus enabling the bacteria to spread and evade many humoral immune mediators. While relatively little is known about the molecular basis forÌýB. pseudomalleiÌý±¹¾±°ù³Ü±ô±ð²Ô³¦±ð in vivo, our research suggests that these bacteria quickly escape the phagosome and evade intracellular killing, preventing bacterial clearance and generation of an effective adaptive immune response. We believe a better understanding of the basic biology of phagocyte subversion by this bacterium would greatly facilitate the development of preventative and curative treatments. We are utilizing the murine model of melioidosis, as well as human in vitro models, to address the following areas:

• Identification of mechanisms that virulentÌýB. pseudomalleiÌýstrains utilize to circumvent efficient clearance by macrophages/neutrophils.
• Identification of outer membrane proteins expressed byÌýB. pseudomalleiÌýthat might serve as virulence factors/vaccine candidates.
• Identification of bacterial mechanisms for evading complement-mediated killing
• Testing vaccines/therapeutics in animal models to assess effectiveness and identify immune correlates of clearance.

Dr. Wooten received his Bachelors (Zoology/Chemistry; 1985) and Masters (Microbiology/Immunology; 1990) from the University of Arkansas (Fayetteville) under the supervision of Dr. Jim Saunders. He received his Ph.D. (Microbiology/Immunology; 1995) from the University of Mississippi Medical Center under the supervision of Dr. Jan Bly. He completed post-doctoral training at the University of Utah College of Medicine in the laboratory of Dr. Janis Weis. Dr. Wooten joined the Department of Medical Microbiology and Immunology at the University of Toledo College of Medicine in May 2001.

Current Funding:

Identification of immunoprotective antigens for preventing Lyme disease
NIH/NIAID (R01)
Period of support: 09/01/2026 - 08/31/2031
Principal Investigator: R. Mark Wooten

Factor H-Fc fusions as novel therapeutics for Burkholderia pseudomallei infections
National Institute of Allergy and Infectious Diseases (R41)
Period of Support: 08/01/23 - 07/31/26
Principal Investigator:Ìý R. Mark Wooten
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Representative Publications: