Center for Microbial Interface Biology

Larry Schlesinger, MD, Director

The Center for Microbial Interface Biology (CMIB), created by Larry Schlesinger, MD, in 2002, was awarded official University center status by the Ohio State University Board of Trustees in December 2006. The CMIB is a multidisciplinary research center focused on microbe-host interactions that promotes and coordinates interdisciplinary research and training opportunities in infectious diseases, microbial pathogenesis and biodefense. The CMIB also manages the Columbus campus Biosafety Level III core research facilities, which are available to the University research community, University collaborating researchers and non-University researchers. In 2006, the CMIB had six core faculty members, and general membership grew to 50 faculty, representing units across the Columbus and Wooster campuses. Research funding for core faculty totaled $5.55 million ($10.55 million in review). These faculty had 20 papers published or in press along with numerous published abstracts. They also had several invited lectureships and review panel appointments, both nationally and internationally.

Ongoing Research Programs

Salmonella antimicrobial peptide resistance (National Institutes of Health/National Institute of Allergy and Infectious Diseases) – John Gunn, PhD. The objective of this award is to further characterize the role of the Salmonella PmrAB regulon, specifically the PmrAB-regulated pmrHFIJKLM operon, in LPS modification, resistance to antimicrobial peptides, and in virulence.
CD8 T cells and immunity to tuberculosis in old mice (National Institutes of Health/National Institute on Aging) – Joanne Turner, PhD. The objective of this award is to understand how CD8 T cells contribute to protective immunity in the elderly during infection with M. tuberculosis.
TB and innate immune regulation of lung macrophages (National Institutes of Health/ National Institute of Allergy and Infectious Diseases) – Larry Schlesinger, MD. The objective of this award is to determine the role of surfactant components in regulating the early interactions between Mycobacterium tuberculosis and macrophages, the host cell niche for this intracellular pathogen.
Characterization of the surface metalloproteases of Trypanosoma cruzi (American Heart Association) – Brad McGwire, MD, PhD. The objective of this award is to better define the role of a major surface metalloprotease, gp63, of Trypanosoma cruzi, the agent of South American trypanosomiasis, in the pathogenesis of disease and its contribution to heart failure

Research Accomplishments of 2006

Lung innate immune responses to Francisella tularensis: a central role for the macrophage (National Institutes of Health/National Institute of Allergy and Infectious Diseases Region V Great Lakes Regional Center of Excellence for Biodefense and Emerging Infectious Disease Research) – Larry Schlesinger, MD. This project studies lung innate immune response to Francisella tularensis, the causative bacterium of tularemia and a targeted agent of bioterrorism. The most worrisome infectious agents of bioterrorism are those that would be artificially disseminated as aerosols to the lungs. Thus, a clearer understanding of lung immune response to these bacteria, especially as they relate to interactions with macrophages, is essential for identifying molecular targets for diagnostic strategies, as well as targeted immune therapies to enhance host immunity. This program project grant includes investigators in both the CMIB and Ohio State’s Davis Heart and Lung Research Institute.
Salmonella antimicrobial peptide resistance (National Institutes of Health/National Institute of Allergy and Infectious Diseases) – John Gunn, PhD. Salmonellae encounter numerous anatomic sites during infection, including the inhospitable environment of the macrophage phagosome, where they are able to survive and replicate. Within host phagocytes and at mucosal surfaces is a potent group of cytotoxic agents (i.e., antimicrobial peptides, or AP). The PmrA-PmrB twocomponent regulatory system is activated when Salmonellae are within host macrophages, and this system is necessary for resistance to AP, which involves modifications of the lipopolysaccharide (LPS) that decrease peptide binding. This study focuses on the PmrA-PmrB regulon, including the identification and characterization of PmrA-PmrBregulated genes necessary for AP resistance and LPS modification, and the determination of the role of PmrA-PmrB-mediated LPS modifications in Salmonella virulence.
In vitro predictors of susceptibility for reactivation tuberculosis (American Lung Association) – Joanne Turner, PhD. Approximately one third of the world’s population is infected with M. tuberculosis; however, only a small portion will develop active tuberculosis. Identifying individuals who are predisposed to reactivate an infection with M. tuberculosis would result in timely intervention and reduce the opportunity for disease transmission. Identifying immunological markers of susceptibility to reactivating an infection would provide such a tool. This grant uses several well-characterized mouse models that are resistant or susceptible to reactivation of a chronic infection with M. tuberculosis to study immunity in the lung and peripheral blood. Studies focus on the relationship between increased IL-10 and a loss of IFN-a production, and on changes that occur at a period of infection that precedes reactivation. Predicting when reactivation is likely to occur would help identify individuals who are progressing toward disease, resulting in timely intervention and reduced disease transmission.
After being awarded official University center status by the OSU Board of Trustees in December 2006, the CMIB moved into the 10th floor of the recently completed Biomedical Research Tower.
CMIB core faculty members had 20 papers published or in press in 2006.
Total research funding for 2006 for CMIB core faculty members was $5.55 million ($10.55 million in review).
Ohio State was established as a member of the National Institutes of Health-funded Great Lakes Regional Centers of Excellence (RCE) in Biodefense and Emerging Infectious Diseases Research Program. CMIB faculty members were awarded a program grant and a development project totaling $1.15 million.
CMIB core faculty received the following awards: - Larry Schlesinger, MD – Donald V. Unverferth Department of Medicine Research Award, Department of Medicine, Ohio State University - Joanne Turner, PhD - American Association of Immunologists Pfizer-Showell travel award
CMIB 2006 awards for research grants included: - Lung Innate Immune Responses to Francisella tularensis: A Central Role For The Macrophage - $1.05 million (includes investigators in both the CMIB and DHLRI) to study lung innate immune responses to Francisella tularensis, the causative bacterium of tularemia and a targeted agent of bioterrorism - Altered M. tuberculosis Mannosylation and the Macrophage - $1.8 million to study the surface carbohydrates of M. tuberculosis that play a central role in pathogenesis

Research Accomplishments of 2005

Year 2 of the Planning Regional Center of Excellence (P-RCE) in biodefense and emerging infectious disease research was completed. This is funded by a $1 million biodefense award from the National Institutes of Health’s (NIH) National Institute of Allergy and Infectious Diseases, which focuses on basic research, immunology and vaccines for organisms with potential for use as bioterrorism agents. This project, led by Larry Schlesinger, MD, allows partner institutions to set up basic science programs essential for dealing with this threat. Along with researchers at Ohio State and Minnesota, scientists from 14 academic and industry partners have taken part.
OSU and members of the CMIB have joined forces with the Great Lakes Regional Center of Excellence (RCE) at the University of Chicago for a research program project grant entitled “Lung innate immune response to Francisella tularensis: A central role for the macrophage.” The grant – submitted by Larry Schlesinger, MD (principal investigator), Mark Wewers, MD, Susheela Tridandapani, PhD, and John Gunn, MD – will help find new molecular targets for therapies and vaccines (i.e., identification of pathways for bacterial entry into cells, characterization of inflammatory pathways activated, and creation of attenuated bacterial mutants for vaccines). These funds will enhance the CMIB’s biodefense portfolio.
The Tzagournis Medical Research Fund Award will fund studies in microbial pathogenesis for a group of scientists who will develop a portfolio in infectious diseases biodefense research. The research team, assembled under the leadership of Larry Schlesinger, MD, involves John Gunn, PhD, Mark Wewers, MD, Paula Bryant, PhD, and Abhay Satoskar, PhD.
The laboratory of John Gunn, PhD, is interested in molecular mechanisms used by Salmonella spp. (which causes typhoid fever) to survive and replicate in the harsh conditions it encounters within human macrophages. Present in these host cells (and at mucosal surfaces) is a potent group of cytotoxic agents called antimicrobial peptides (AP). The bacteria activate a two-component regulatory system to survive within macrophages and resist AP, in part by modifying major sugars (LPS) on the bacterial surface. Gunn’s lab studies how this regulatory system works, including identification and characterization of regulated genes necessary for AP resistance and LPS modification, and their role in Salmonella virulence. His lab also studies chronic infection of the human gallbladder in Salmonella carriers, hoping to understand: (1) how Salmonella is able to sense bile, (2) what mechanisms of bile resistance exist in Salmonella, and (3) how biofilm formation on gallstones/gallbladder epithelial cells may help develop the carrier state.
Joanne Turner, PhD, focuses on changes that take place in the immune system during aging and the influence that they have on host capacity to control infectious diseases. Many facets of immune response decline with age, in particular within the CD4 T cell compartment; however, it is also likely that alternative immune mechanisms arise that can compensate for these changes. Understanding how these alternative immune responses participate during infection may help develop vaccines or post-exposure therapies for an aging immune system. Turner’s research examines the function of CD8 T cells and macrophages within the lungs of old mice in response to infection with M. tuberculosis. She is also identifying immune responses that correlate with an individual’s susceptibility to reactivate a previously latent infection with M. tuberculosis.
Brad McGwire, MD, PhD, received an American Heart Association grant to study the protozoan parasite Trypanosoma cruzi, the agent of South American trypanosomiasis and a leading cause of heart failure in Latin America. Genes encoding the surface metalloproteases (gp63) of this parasite are structurally related to those in other protozoa such as Leishmania. In Leishmania, gp63 is an important virulence factor that has been well characterized at the genetic, biochemical and cell biologic levels. McGwire’s laboratory has begun the biochemical characterization of gp63s in T. cruzi (TcGP63). These studies will provide information on TcGP63s and help in understanding the role of these proteases in the biology of T. cruzi and how they may contribute to heart failure.

Center for Microbial Interface Biology
N1149 Doan Hall
410 West 10th Avenue
Columbus, OH 43210
(614) 293-5671