New research by scientists at two University of Maryland, Baltimore schools (UMB) is highlighted in a special issue of Pathogens and Disease.
The issue, which includes work by scientists at the UM School of Medicine (UMSOM) and UM School of Dentistry (UMSOD) focuses on key issues in infection and immunity, which are crucial research areas at the institution.
It includes 22 articles, mini-reviews, and commentaries on a range of infectious agents, including Ebola and Clostridium difficile, as well as new vaccine approaches at the UMSOM Center for Vaccine Development and comparative genomics studies of protozoan parasites at the UMSOM Institute for Genome Sciences.
“I’m very proud to be a part of this undertaking,” said one of the editors of the issue, James B. Kaper, PhD, senior associate dean for academic affairs and professor and chair in the Department of Microbiology and Immunology at UMSOM. “From biofilms to Ebola, this work by scientists at UMSOM and UMB is really advancing our knowledge in important ways.”
“This special issue, focusing on the work of one institution, provides a time capsule of the state-of-the-art research being done at UMB in infectious disease and immunity research,” said editor-in-chief of Pathogens and Disease, Patrik Bavoil, PhD, professor and chair of the Department of Microbial Pathogenesis at UMSOD and adjunct professor in the Department of Microbiology and Immunology at UMSOM. “It also provides a glimpse of the collaborative spirit between the School of Medicine and the School of Dentistry in terms of infectious disease research.”
One article details an investigation into the antibiotic-resistant superbug Clostridium difficile, which causes 30,000 deaths in the United States each year and for which, as yet, no effective prevention is available. Antibodies against the bacterial toxins, the culprit of the disease, have proven to be protective against the infection in animal disease models and in clinical trials. However, antibodies are impractical for prevention due to their high cost and short life in serum after delivery. In this study, Hanping Feng, PhD, professor in the Department of Microbial Pathogenesis at UMSOD and adjunct associate professor in the Department of Microbiology and Immunology at UMSOM, and his colleagues engineered an attenuated virus for delivering anti-toxin antibodies. They demonstrated that virus-infected mice express highly potent anti-toxin antibodies that are fully protective against both primary and recurrent C. difficile infection for up to two months. This novel strategy has great potential for the prevention against C. difficile infection.
Another article, co-authored by Alison J. Scott, PhD, research associate professor in the Department of Microbial Pathogenesis at UMSOD, along with Robert K. Ernst, PhD, professor in the Department of Microbial Pathogenesis at UMSOD and an adjunct professor in the Department of Microbiology and Immunology at UMSOM, focused on new methods and tools to investigate lipid A, advancing the study of lipids in the interactions of bacteria and their hosts. The researchers improved the ability to detect host and bacterial lipids as much as 100-fold, employing the matrix norharmane in mass spectrometric imaging experiments. The paper highlights paths for improving the understanding of how pathogens interact with their animal and human hosts. Images taken from the article by Scott and Ernst are reproduced here in the upper portion of the illustration. These are host-pathogen lipid images from Francisella novicida infected mouse spleens using mass spectrometry imaging.
Alan Schmaljohn, PhD, a professor in the Department of Microbiology and Immunology at UMSOM, along with George Lewis, PhD, a professor of microbiology and immunology at UMSOM and director of the Division of Vaccine Research at the UMSOM Institute of Human Virology, co-authored a review paper looking at how Ebola antibodies provide protection. It appears that many Ebola antibodies work not primarily by neutralizing the virus, but by targeting cells that have already been infected by the virus. By doing this, the cell-targeting antibodies decrease transmission of the virus from infected cells to healthy cells. The paper illustrates the complex ways by which these antibodies protect against the disease.
A graphic taken from the article by Schmaljohn and Lewis is reproduced here in the lower portion of the illustration. Contrary to the view that “virus neutralization” is the only means of antibody-mediated protection, antibody molecules that arise after vaccination or infection may have multiple antiviral functions (shown as areas of overlap), and neutralization is not always necessary or sufficient to provide immunity (shown as sets of antibodies that protect animals but do not neutralize virus).
Tonya Webb, PhD, an associate professor in the Department of Microbiology and Immunology at UMSOM, contributed two papers. In one, she focuses on sphingosine 1-phosphate (S1P), a molecule that plays a key role in immunity and inflammation. She argues that it may be possible to target the S1P pathway as a way to fight cancer.
In another. Webb also looked at the central signaling pathways that activate the innate immune system. One of these pathways is the AMPK pathway, which gets activated during viral infection. Webb and her colleagues found that the pathway is also active in human tumor cells. This finding has potential clinical significance, because there are certain drugs that can induce activation of the AMPK pathway, including the already-approved diabetes drug Metformin. Treatment with these drugs might increase the ability of the immune system to recognize and kill cancer cells.
“This cutting-edge work really shows the breadth and depth of the work being done here on infection and immunity,” said UMSOM Dean E. Albert Reece, MD, PhD, MBA, who is also the University vice president for medical affairs and the John Z. and Akiko K. Bowers Distinguished Professor. “Our scientists are using so many exciting approaches and so many tools to analyze and unravel these urgent real-world problems, and I know that this work will continue, and will eventually lead to real-world solutions.”
“The research being conducted here at the School of Dentistry and School of Medicine will significantly advance our understanding of the treatment and prevention of an array of infectious diseases. This issue highlights some of the innovative, collaborative work at the University of Maryland,” said UMSOD Dean Mark A. Reynolds, DDS, PhD, MA.
The illustration contains excerpts from the special issue and a design courtesy of Oxford University Press showing elements of the cover of Pathogens and Disease and the logo of the Federation of European Microbiological Societies.