Joseph Edward Qualls, Ph.D.

Joseph Edward Qualls, Ph.D.

Institution: Children's Hospital Medical Center

Project: Lactate metabolism and host defense against Mycobacterium tuberculosis

Grant(s): Innovation Award

One quarter of the world population is persistently infected with Mycobacterium tuberculosis (Mtb), resulting in more than 1.5 million deaths annually from active tuberculosis (TB). Considering the rapid development of resistance against common antibiotic therapies targeting Mtb, new approaches designed to augment the body’s immune defenses are urgently needed. Lactate (a substance produced during cell metabolism) and its synthesis are associated with Mtb infection, especially within macrophages—immune cells central to the body’s anti-TB response. We will examine the contribution of lactate synthesis during the body’s anti-TB immune response using experimental models of Mtb infection. We anticipate the results may lead to novel host-directed approaches aimed at supplementing current antibiotic therapies.

Update:

Over the past year we have begun characterizing a mouse infection model where macrophages and other blood cells called myeloid cells are unable to produce the enzyme responsible for synthesizing lactate (Ldha). Using this model, combined with cell culture and infection experiments, we have preliminary data about Ldha activity in macrophages. We have found that it assists in macrophage anti-mycobacterial activity and may alter peripheral immune cell function in Mtb-infected tissues.

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