Mycoplasma gallisepticum interactions with epithelial cells: A model to study the biology of mycoplasma cell invasion and intracellular parasitism

Until very recently organisms of the genus Mycoplasma, now numbering over 100 species, were described as extracellular parasites which cause chronic diseases in man and animals. The discovery of the human pathogen M. penetrans as intracellular organism has changed the view of many microbiologists regarding the strategies employed by these very simple prokaryotes to survive and persist within immunocompetent hosts. Recently, three other human mycoplasmas, M. fermentans, M. genitalium and M. pneumoniae, that colonize both the respiratory tract and/or the urogenital tract, were shown to invade eukaryotic cells. While most pathogenic mycoplasmas are surface parasites and establish localized chronic infections, certain species have the capacity to become invasive, i.e. they are able to translocate across the mucosal barriers and cause systemic infections after entering the bloodstream, yet little is known about the pathogenesis of tissue translocation events or mycoplasma virulence factors involved in these infections. Internalization of mycoplasmas by the mammalian cell may play a crucial role in the disease process and may be a strategy which enables these organisms to passage through the mucosal epithelial cell barriers and gain access to various locations in the host. However, mechanisms by which mycoplasmas invade the host cell, exploit signal transduction pathways and persist intracellularly have not yet been elucidated. The major objective of this research project focuses on the avian pathogen Mycoplasma gallisepticum as a model organism to study the invasion process of mycoplasmas into nonphagocytic eukaryotic cells. This research proposal is divided in two parts. The first one focuses on the characterization of M. gallisepticum invasion into eukaryotic cells and the comparison of invasion frequencies between a virulent and a non-virulent passage of the same strain. The second part concentrates on identifying mycoplasma genes and their products involved in the invasion process. Collectively, information gained from this study will provide new insights into the molecular events that occur when M. gallisepticum interacts with epithelial cells, and more specifically, whether and how this particular pathogen functions as intracellular parasite. This information will also contribute to our increased understanding about the molecular basis of M. gallisepticum pathogenicity which may ultimately lead to new therapeutic strategies.