We are a group of scientists at Indiana University who study the biology of intracellular pathogens - bacteria and parasites that must reside inside of another cell (a host cell) in order to grow and replicate.
Intracellular pathogens cause a number of different infectious diseases that are particularly challenging to treat and eliminate from the body.
Information about the intracellular pathogens studied in our laboratories can be found below.
Plasmodium spp. causes the dreaded disease malaria, which kills up to one million people each year, many of which are children. Drug-resistance and the lack of an effective vaccine have partnered to make malaria one of the most significant global health burdens of our age. Plasmodium parasites are transmitted by the mosquito and migrate to the liver and then invade red blood cells. As the parasites replicate and destroy red blood cells, some differentiate into sexual forms that are taken up by a mosquito to transmit the parasite to a new host.
Toxoplasma gondii infects virtually all vertebrates and is present in over 1/3 of the human population. Toxoplasma completes its sexual cycle only in cats, which can shed infectious oocysts into the environment. We and other animals can become infected through these oocysts in the soil or water. Upon infection, the parasite replicates inside host cells and forms tissue cysts (shown in photo to the left) that cannot be eradicated by the immune response or current drug treatments. The tissue cysts give rise to another means of transmission through predation; in other words, eating undercooked meats. Toxoplasma can also be transmitted to a fetus if the mother becomes infected for the first time during pregnancy. The tissue cysts can "reactivate" if the person becomes immune compromised, so toxoplasmosis typically arises as an opportunistic infection in AIDS or organ transplant patients. Toxoplasma has also been linked to neurological disorders such as schizophrenia.
Multiple obligatory intracellular bacterial pathogens in the genus Chlamydia are important human pathogens. For example, different C. trachomatis strains are the leading global causes of bacterial sexually transmitted infection and infectious blindness (trachoma). C. pneumoniae is an important cause of community acquired pneumoniae and possibly atherosclerosis. Finally, C. psittaci can cause lethal disseminating pneumonia. These pathogens share a complex intracellular developmental cycle in which they alternate between intracellular replicative reticulate body and extracellular infectious elementary body forms. Chlamydia infections can be long-lasting and there is increasing evidence that some of these pathogens may be able to enter viable but not culturable persistent states that allow them to persist in their hosts and possibly evade immunity. The epidemiology of chlamydial infections is complex and species-specific but known routes of infection by pathogens in this group include sexual contact, respiratory transmission, autoinoculation, fomites and fecal-oral transfer.
The bacterial pathogen Coxiella burnetii is the causative agent of human Q fever, an emerging infectious disease and leading cause of culture-negative endocarditis. Coxiella is primarily a zoonotic pathogen, with sheep and goats being the major source of human infection. Spread of the bacteria is facilitated by low infectious dose (<10 organisms), environmental stability, and aerosol transmission. Coxiella is an obligate intracellular bacterial pathogen that targets macrophages and replicates in a modified lysosome-like parasitophorous vacuole (PV). Once inside, Coxiella remodels the host cell, manipulating a broad range of processes from endosomal trafficking to the host immune response.