A group of researchers at the University of Texas Medical Branch at Galveston (UTMB) have found a way to block an abnormal pathway that may defeat some of the world’s most devastating infections. Rickettsioses are a group of insect-borne disease carried by bacteria. The investigators at UTMB have discovered a way to protect against rickettsial infection. According to Dr. David Walker, chairman of the department of pathology at UTMB and executive director for the Center for Biodefense and Emerging Infectious Diseases, “Even more exciting, there is preliminary evidence that the experimental drug we have identified as being effective against rickettsiae may also be effective against viruses.”
A number of scientists are concerned about possible widespread cases of rickettsioses that some link to global warming theory. Bacteria are carried and spread by ticks, lice, fleas and chiggers all of which tend to thrive in warmer climates. Walker notes that, since the bacteria are easily transmitted, they could pose a bioterrorism threat.
Rocky Mountain spotted fever is another disease, a potentially lethal one, brought about by rickettsial with a fatality rate of 32 percent in patients who have Mediterranean spotted fever. Walker notes, “We believe that it is imperative that we find a way to control this disease.”
Signals to cells can be controlled by a messenger molecule known as cyclic AMP. Cyclic AMP plays an important role in the development of a number of human diseases including diseases caused by bacteria and viruses. The effects of this messenger are controlled by two types of receptors. One is known as a protein kinase A (PKA) and the other is known as Epac (newly identified). Epac and PKA act together or in opposition to control a number of cellular functions.
Dr. Bin Gong and Dr. Xiaodong Cheng, research collaborators at UTMB, worked with a mice model that had the gene for Epac receptor inactivated. They observed that mice infected with deadly Rickettsia bacteria were resistant to fatal infection.
The underlying mechanism for this discovery is being identified. Moreover, a new candidate drug that inhibits Epac known as ESI (Epac-specific inhibitor), has been demonstrated to protect normal mice from a fatal rickettsial infection. Currently, the investigators are developing a second-generation ESI that is more potent and non-toxic at high doses. They observed that ESI has the ability to protect animals from lethal viruses as well.
Walker notes, “This is an exciting development, given that our arsenal of treatments for these bacteria is quite limited.”