Many bacteria possess the extraordinary ability to invade, replicate, and persist within host cells. However, an understanding of the molecular mechanisms mediating these processes has remained elusive. The long-term objective of this research is to illuminate the way in which the intracellular bacterial pathogen Brucella melitensis interacts with host cells. The specific research objectives of this effort are to define the molecular mechanisms by which inositol-requiring enzyme-1 (Ire1), an important regulator of the cell's response to stress, supports B. melitensis movement and replication in host cells. In addition, this research will examine whether additional candidate genes participate in this process. Taken together, this research will provide insight into the molecular mechanisms by which intracellular bacterial pathogens invade, replicate, and persist in the host, and thereby, have a broad scientific impact.
Important educational objectives will be pursued in parallel with these research aims. These objectives include expanding graduate student recruiting activities at Hispanic Serving Institutions in the Texas Rio Grande Valley and U.S.-Mexico border regions. This enhanced recruiting effort will help attract students from diverse backgrounds into life science and agriculture graduate programs at Texas A&M University. In addition, this research will provide research opportunities for highly motivated undergraduates. The Rio Grande Valley and U.S.-Mexico border regions experience the highest incidences of human brucellosis (the disease caused by Brucella infection) in the nation. Therefore, the commitment to train students from these regions will create unique opportunities for integrating the specific research activities in elucidating Brucella pathogenesis with the concerns of affected communities.
Infectious diseases caused by bacterial pathogens contribute significantly to global disease burden. Brucella is one such pathogen and the causative agent of brucellosis, a worldwide zoonosis of profound importance. In humans, brucellosis typically presents in the clinic as an undulant fever, but gradually becomes systemic, affecting practically every organ system of the body. Brucellosis has eluded systematic attempts at eradication for more than a century, even in most developed countries, and no approved human vaccine is available. Moreover, Brucella is highly infectious when delivered via the aerosol route. Human brucellosis is associated with low rates of mortality and high rates of morbidity, and hence, Brucella has the potential to render opposing forces severely debilitated, and significantly tax battlefield or urban hospital and healthcare resources. Although combination antibiotic therapy can be used to treat infection, typical treatment regimens are prolonged and often accompanied by side effects. The research supported by this awared was broadly directed toward elucidating the molecular mechanisms by which Brucella interacts with the host with the understanding that insights gained from this investigation will advance the long-term goal of developing new therapies and/or vaccines for addressing brucellosis. The work succeeded in identifying several new factors in the host that mediate infection. These factors include key molecules that regulate the ability of the host to respond to stress. Future studies will investigate how these molecules can be targeted to decrease disease incidence and burden. The work also supported the training of undergraduates in the art and craft of scientific research. In addition, undergraduates were provided with opportunities to generate enthusiasm for science and scientific research through participation in Invisible Jungle, an educational radio program that gives the general public a glimpse into the fascinating and invisible world of microbiology. Finally, the investigators on this proposal participated in HESTEC, a regional event that engages the public in the Rio Grande Valley of South Texas in learning about science. Hundreds of students were exposed to scientific research through this endeavor.
