Glycerol contributes to tuberculosis susceptibility in male mice with type 2 diabetes

Diabetes mellitus increases risk for tuberculosis disease and adverse outcomes. Most people with both conditions have type 2 diabetes, but it is unknown if type 1 and type 2 diabetes have identical effects on tuberculosis susceptibility. Here we show that male mice receiving a high-fat diet and streptozotocin to model type 2 diabetes, have higher mortality, more lung pathology, and higher bacterial burden following Mycobacterium tuberculosis infection compared to mice treated with streptozotocin or high-fat diet alone. Type 2 diabetes model mice have elevated plasma glycerol, which is a preferred carbon source for M. tuberculosis. Infection studies with glycerol kinase mutant M. tuberculosis reveal that glycerol utilization contributes to the susceptibility of the type 2 diabetes mice. Hyperglycemia impairs protective immunity against M. tuberculosis in both forms of diabetes, but our data show that elevated glycerol contributes to an additional adverse effect uniquely relevant to type 2 diabetes. Patients with diabetes mellitus have an increased risk of developing tuberculosis. Here the authors show that increased blood levels of glycerol in mice with type 2 diabetes contributes to their susceptibility to infection, as glycerol is one of the main carbon sources for the bacteria.

Automated summary

Diabetes mellitus, especially type 2 diabetes, increases the risk of developing tuberculosis. In a mouse model, it was found that mice with type 2 diabetes, induced by a high-fat diet and streptozotocin, had higher mortality, more severe lung pathology, and higher bacterial burden following Mycobacterium tuberculosis infection compared to mice treated with streptozotocin or high-fat diet alone. The elevated plasma glycerol level in the type 2 diabetes model mice was found to contribute to their susceptibility to infection, as glycerol is a preferred carbon source for M. tuberculosis.