Roberto N. De Guzman

A major focus of our lab is on NMR studies of protein-protein complexes involved in the assembly of bacterial needles. Many bacteria rely on an external needle to infect millions of people worldwide and many are potential agents of bioterrorism. Annually, Shigella alone is estimated to cause up to 1.1 million deaths worldwide, including 350,000 deaths in young children. There are still sporadic outbreaks of Yersinia pestis, which caused the Black Death in Europe during medieval times. Among cystic fibrosis patients, secondary lung infection by Pseudomonas aeruginosa is the major cause of death. No vaccines are currently approved for general use against any of these pathogens, and more alarmingly, many have developed multidrug resistance to current antibiotics. Because the needle apparatus is exposed on the bacterial surface and plays a critical role in virulence, disrupting the needle assembly is an attractive approach for the development of novel anti-infectives. This approach requires a detailed understanding of the protein-protein interactions involved in needle assembly.

 

Another major effort is the structural studies of protein-protein and protein-RNA interactions involved in the assembly of hantavirus. The hantaviruses are enveloped RNA viruses, and can cause two deadly emerging infectious diseases in humans: the hantavirus hemorrhagic fever with renal syndrome (HFRS) and the hantavirus cardiopulmonary syndrome (HCPS). HFRS is more common in Asia and Europe where in severe cases, patients suffer from vascular leakage, kidney failure, and death. HCPS was first identified in the United States in 1993 during an outbreak in the Four Corners area where Utah, Arizona, New Mexico, and Colorado meet. That outbreak was caused by a novel species, the Sin Nombre virus, and had an initial fatality rate of 80% where patients died from heart failure and respiratory collapse.