Bacterial Pathogenesis

Of all the known bacterial species, only a few are pathogenic to humans. Those that are can be quite nasty and even deadly in some cases. One massive human epidemic during the Middle Ages, the Black Death or Plague, wiped out over one-third of the population of Europe.

Interest in Plague has intensified recently because of the emerging threat of bioterrorism. The disease is caused by the gram-negative bacteria Yersinia pestis. An important factor in the virulence of Y. Pestis is its ability to survive and proliferate inside phagocytic cells rather than be killed by them. A group of proteins known as Yops (Yersina outer proteins) counteract natural defense mechanisms and help the bacteria multiply and disseminate in the host. Recent advances in the field have shown that Yops are structurally and functionally diverse, including protein kinases, protein phosphatases, proteases and GAP molecules. Our goal is to understand the molecular mechanisms by which various Yops function in human cells and how we can defeat them.

Structure Gallery:

AvrPphB

More Readings:

Cornelis GR. Molecular and cell biology aspects of plague. (2000) PNAS USA 97(16):8778-83.

Galan JE, Collmer A. Type III secretion machines: bacterial devices for protein delivery into host cells. (1999) Science 284(5418):1322-8.

Boyd AP, Lambermont I, Cornelis GR. Competition between the Yops of Yersinia enterocolitica for delivery into eukaryotic cells: role of the SycE chaperone binding domain of YopE. (2000) Journal of Bacteriology 182(17):4811-21.

Zumbihl R, Aepfelbacher M, Andor A, Jacobi CA, Ruckdeschel K, Rouot B, Heesemann J. The cytotoxin YopT of induces modification and cellular redistribution of the small GTP-binding protein RhoA. (1999) Journal of Biological Chemistry 274(41):29289-93.