Listeria monocytogenes infection and the host cell cycle

• Applicant: Dr. Marieluise Kirchner
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2007 to 2009
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 37374154

Many infectious diseases are caused by pathogens that replicate inside of human cells (intracellular pathogens). Listeria monocytogenes (Lm) is an intracellular bacterial pathogen that infects a wide variety of cell types and is well adapted to replicate within the cytosol (cytoplasm) of host cells. As human cells grow and divide the progress through a defined series of stages termed the cell cycle. Our studies indicate that Lm infection may be increased within non-dividing cells. The focus of this proposal is to elucidate the role of the host cell cycle during LM infection. In Aim I, we will determine if Lm infection alters host cell cycle progression. Cell cycle phase distribution, cell proliferation, and cell division event will be analyzed to determine alternations induced by infection. In Aim II, we will determine if host cell cycle arrest at specific stages promotes Lm infection. Genetic and pharmacological inhibitors will be used to block host cell cycle progression at defined stages and arrested cells will be infected with Lm. To determine specific steps of bacterial infection that may be affected, analysis of bacterial entry, intracellular replication rates, and cell-to-cell spread will be performed. Host cell and pathogen specificity will be verified by analyzing multiple host cell types and by comparison to infections with other intracellular bacterial pathogens. These studies will provide insights into how bacterial pathogens that replicate in the cytosol adapt to the intracellular environment or control host cell functions to promote intracellular infection.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Dr. Darren E. Higgins