Lokesh Sharma, Ph.D.
Funded by the American Lung Association of the Northeast
Gene Deficiency Linked to Increased Pneumonia Survival
Klebsiella pneumoniae is a germ that causes pneumonia, with a mortality that can reach up to 70 percent when infection spreads to other organs. Current, antibiotic treatment often fails due to development of antibiotic resistance, so there is an urgent need for new therapies. We have found a deficiency in a gene called Chit1, present in up to 20 percent of humans, gives mice a significant advantage during pneumonia. Absence of this gene helps mice limit bacterial spread to other organs and increase survival with or without antibiotic use. Understanding the mechanisms of the advantage provided by Chit1 deficiency will help to develop new therapies that can boost the host defense against bacterial infection to reduce mortality.
Update: We found that white blood cells called macrophages from Chit1-deficient mice have enhanced ability to kill klebsiella pneumoniae (Kp), which is associated with increased activation of a key molecule called Akt. We found that these effects are specific to Kp lung infection and not shared by other similar bacteria. We are exploring whether losing the enzymatic activity of the Chit1 molecule is enough to provide a survival advantage during Kp lung infection or if this molecule plays its role during infection by a different mechanism.