Research in our laboratory focuses on understanding the mechanisms that lead to infection of the placenta. The placenta is an extraordinary organ, differing from others because it has to protect the fetus from rejection by the maternal immune system and from pathogens. Thus, the placenta has to provide an environment of immune tolerance and host defense at the same time. How this is achieved is largely unknown. Out of the myriad of microbes only a few are known to infect the placenta, which suggests that the placenta has strong defensemechanisms. The known placental pathogens include a few viruses, bacteria, and protists. Interestingly, these disparate organisms have one thing in common: they have intracellular life cycles. Among these is the bacterium Listeria monocytogenes and the protist Toxoplasma gondii. Our lab has investigated both of these pathogens. However, we are predominantly using L. monocytogenes, a well-characterized intracellular pathogen that is highly amenable to experimental analysis and thus provides us with valuable molecular tools. A major limitation to our understanding of placental and fetal infections has been the lack of an animal model for human disease. The mouse is not a good model. Therefore, we developed a pregnant guinea pig model of listeriosis that replicates human disease, and we have used it to identify listerial virulence determinants that are important for bacterial growth in the placenta in vivo. In order to perform in vitro experiments in a physiologically highly relevantmodel system we are using primary human placental organ and cell culture models. With these tools in hand we are attempting to improve our understanding of the molecular and cellular mechanisms of host-pathogen interactions in the placenta, which will shed insights into mechanisms of prematurity and congenital infections.
Bakardjiev AI, Stacy BA, Fisher SJ, Portnoy DA. Listeriosis in the pregnant guinea pig: a model of vertical transmission. Infection and Immunity. 72(1): 489-497, 2004
Bakardjiev AI, Stacy BA, Portnoy DA. Growth of Listeria monocytogenes in the Guinea Pig Placenta and Role of Cell-to-cell Spread in Fetal Infection. Journal of Infectious Diseases. 191:1889-97, 2005
Bakardjiev AI, Theriot J and Portnoy DA. Listeria monocytogenes traffics from maternal organs to the placenta and back: a new role for the placenta during listeriosis. PLoS pathogens 2(6):e66, 2006
Robbins JR, Skrzypczynska KM, Zeldovich VB, Kapidzic M and Bakardjiev AI. Placental syncytiotrophoblast constitutes a major barrier to vertical transmission of Listeria monocytogenes. PLoS pathogens 6(1):e1000732.doi:10.1371, 2010
Maltepe E, Bakardjiev AI and Fisher SJ. The placenta: Transcriptional, Epigenetic, Physiological Integration During Development. Journal of Clinical Investigation. 120(4):1016-25, 2010
Zeldovich VB, Robbins JR, Kapidzic M, Lauer P, and Bakardjiev AI. Invasive Extravillous Trophoblasts Restrict Intracellular Growth and Spread of Listeria monocytogenes. PLoS pathogens 7(3): e1002005. doi:10.1371/journal.ppat.1002005, 2011
Jody Melton-Witt J*, Susanne Rafelski S*, Daniel Portnoy DA, and Bakardjiev AI. 0ral infection with signature-tagged Listeria monocytogenes reveals organ-specific growth and dissemination routes in guinea pigs. Infection and Immunity 80(2):720-32, 2012
Robbins JR, Zeldovich VB, Poukchanski A, Boothroyd JC, and Bakardjiev AI. Tissuebarriers of the human placenta to infection with Toxoplasma gondii. Infection and Immunity 80(1):418-28, 2012
Robbins JR and Bakardjiev AI. Pathogens and thePlacental Fortress. Current Opinions in Microbiology. 15(1):36-43
Wasilewski M, Rafelski SM, Robbins JR, Bakardjiev AI, and Scorrano, L. Opa1 controls steroidogenesis in trophoblasts. Current Biology 22:1-7, 2012
Zeldovich VB, Bakardjiev AI. Host defense and tolerance: unique challenges in the placenta. PLoS Pathog. 2012;8(8):e1002804. doi: 10.1371/journal.ppat.1002804. Epub 2012 Aug 9.
Vigliani MB, Bakardjiev AI. First trimester typhoid Fever with vertical transmission of salmonella typhi, an intracellular organism. Case Rep Med. 2013;2013:973297. doi: 10.1155/2013/973297. Epub 2013 Dec 29. PMID: 24459469
Zeldovich VB, Clausen CH, Bradford E, Fletcher DA, Maltepe E, Robbins JR, Bakardjiev AI. Placental syncytium forms a biophysical barrier against pathogen invasion. PLoS Pathog. 2013 Dec; 9(12):e1003821. doi: 10.1371/journal.ppat.1003821. Epub 2013 Dec 12. PMID: 24348256