The Department of Molecular Microbiology and Immunology's (MMI) mission is to maintain active and integrated research programs that study the interactions between microbes and their hosts. The goal is to understand how these influence the outcome of infection and disease progression. Current research interests in the department include understanding host signaling in response to viral infection, molecular mechanisms of NK and NK T cell activation, and molecular principles underlying fungal pathogenesis. This work provides an interdisciplinary structure for our training programs.
MMI supports undergraduate, graduate, and postdoctoral education in the areas of microbiology and immunology. Departmental instruction includes lecture courses, seminar courses, and laboratory research (both undergraduate independent study and graduate thesis). We foster collaborative studies within the department as well as with faculty in other departments, both on campus and hospital-based.
Cross-Domain and Viral Interactions in the Microbiome
The importance of the microbiome to human health is increasingly recognized and has become a major focus of recent research. However, much of the work has focused on a few aspects, particularly the bacterial component of the microbiome, most frequently in the gastrointestinal tract. Yet humans and other animals can be colonized by a wide array of organisms spanning all domains of life, including bacteria and archaea, unicellular eukaryotes such as fungi, multicellular eukaryotes such as helminths, and viruses. As they share the same host niches, they can compete with, synergize with, and antagonize each other, with potential impacts on their host. Here, we discuss these major groups making up the human microbiome, with a focus on how they interact with each other and their multicellular host.
Coinfection With Influenza A Virus and Klebsiella oxytoca: An Underrecognized Impact on Host Resistance and Tolerance to Pulmonary Infections
The During the influenza season an average of 20% of the human population is infected, with this percentage varying from year to year depending on the virulence of the strains circulating that season. Secondary bacterial pneumonia following influenza A virus (IAV) infection is a serious complication whose prevalence and severity correlates with the virulence of the influenza strain. On average, 0.5% of previously healthy, young individuals and 2.5% of elderly or immunocompromised patients that contract IAV have bacterial coinfections; however, during times of influenza pandemic these numbers climb even higher and in the 1918 influenza virus pandemic up to 6.1% of all patients with IAV were thought to have secondary bacterial infections. In 1918, prior to the use of antibiotics, autopsies confirmed the presence of bacteria in up to 95% of fatalities. In the 2009 pandemic between 18 and 34% of IAV patients in the ICU had a bacterial coinfection and up to 55% of fatalities were associated with bacterial coinfection.
Pulmonary influenza A virus infection leads to suppression of the innate immune response to dermal injury
The innate immune response to lung infection takes priority at the expense of wound healing, according to a study published August 23 in the open-access journal PLOS Pathogens by a team of researcher at Brown University led by Amanda Jamieson. The innate immune system is responsible for responding to infections, clearing cancerous cells, healing wounds, and removing foreign substances. Although many of these functions happen simultaneously in life, most laboratory studies of the innate (or early) immune response focus on one activity. How the innate immune system responds to concurrent insults in different parts of the body is not well understood. To address this question, Dr. Meredith Crane, Dr. Amanda Jamieson and colleagues set out to determine the impact of a respiratory infection on wound healing.
Antifungal tolerance is a subpopulation effect distinct from resistance and is associated with persistent candidemia
Population heterogeneity is an important strategy that pathogens can utilize to escape antimicrobial treatment. This is now evidenced by our work in Candida albicans, a prevalent fungal pathogen that can occupy diverse niches in the human body, either as a commensal or as an invasive pathogen. Antifungal resistance has been described for all drugs used to treat infections by this species. Frontline therapies include azoles, a class of drugs which target the fungal cell membrane and inhibit cell growth. We now show that population heterogeneity of infecting isolates can enable azole escape – in many strains a subpopulation of C. albicans cells can still grow, albeit slowly, in the presence of high drug concentrations.
Surviving Deadly Lung Infections: Innate Host Tolerance Mechanisms in the Pulmonary System
Much research on infectious diseases focuses on clearing the pathogen through the use of antimicrobial drugs, the immune response, or a combination of both. Another way to survive an infection is to tolerate the alterations to homeostasis that occur during a disease state through a process called host tolerance or resilience, which is independent from pathogen burden. Alterations in homeostasis during infection are numerous and include tissue damage, increased inflammation, metabolic changes, temperature changes, and changes in respiration. By understanding tolerance mechanisms in the lung we can better address treatment options for deadly pulmonary infections.