Cell–pathogen interactions (viruses and bacteria)

This was a diverse session reflecting the many different mechanisms utilized by viral and bacterial pathogens to modulate and affect host cell biology. The talks and the lively question and answer sessions that followed ranged from discussing the impact of pathogens on generating the optimal cellular milieu for replication and assembly to understanding the host cell antipathogenic response. Scott Grieshaber (Florida State University) started off the session by describing how Chlamydia trachomatis promotes early exit from mitosis in infected cells. This obligate intracellular pathogen targets the spindle assembly checkpoint, which is necessary for organized cell division, by functionally inactivating cyclin B1 and cyclin-dependent kinase 1 via the activity of the chlamydial pro-tease-like activity factor, or CPAF. Infected cells enter prematurely into anaphase, causing an increased rate of DNA tangles and failure of cytokinesis. David Shifrin (Vanderbilt University) presented evidence for a novel mechanism for battling pathogenic enteric bacteria in which intestinal epithelial cells shed vesicles into the gut lumen. Vesicle shedding is up-regulated by the presence of enteropathogenic and other Gram-negative bacteria. The vesicles are loaded with intestinal alkaline phosphatase, which dephosphorylates and inactivates bacterial lipopolysaccharides. Shifrin also showed that these vesicles directly adhere to the bacterial surface, and this adherence may mediate the observed loss in bacterial adhesion to intestinal epithelial cells and bacterial growth. Pascale Cossart (Institut Pasteur) showed that the intracellular pathogen Listeria monocytogenes causes transient fragmentation of the mitochondrial network early in infection. The secreted, pore-forming toxin listeriolysin O was identified as the main bacterial factor responsible for disruption of the mitochondrial network and for mitochondrial function modulation. Transient disruption of mitochondrial dynamics and function may represent a novel strategy used by pathogenic bacteria to interfere with cellular physiology. Sandy Simon (Rockefeller University) demonstrated the power of live-cell microscopy in dissecting the assembly of single HIV viri-ons at the plasma membrane. He demonstrated that HIV Gag molecules must be myristoylated for genome recruitment, and these Gag molecules only assemble after engaging the HIV genome. He also showed that budding of HIV from the plasma membrane is mediated by the contemporaneous recruitment of ESCRTIII and VPS4 ATPase, which then dissociate from the nascent virion. Leigh Knodler (National Institute of Allergy and Infectious Diseases , National Institutes of Health) described a subpopulation of intracellular Salmonella typhimurium that hyperreplicates in the cy-tosol of epithelial cells. Unlike intravacuolar Salmonella, these cyto-solic bacteria are induced for the invasion-associated type III secretion …