Infection with Staphylococcus aureus can cause insulin resistance in mice, according to new research published in Nature Microbiology.

S. aureus infection is known to occur at increased frequency in some patients with obesity and type 2 diabetes mellitus. In addition, evidence suggests that S. aureus disrupts the immune system, which can lead to insulin resistance. However, the mechanistic link between S. aureus infection and insulin resistance is unknown, prompting Yu Liu and colleagues to undertake a mouse study to try and elucidate the connection.

The researchers generated a mouse model of S. aureus infection, which exhibited impaired glucose tolerance. A screening assay revealed seven functional extracellular S. aureus proteins. Of these seven proteins, they found that only the extracellular enzymatic domain for lipoteichoic acid synthase (eLtaS), which is released by S. aureus, bound to insulin. Using an enzyme-linked immunosorbent assay (ELISA), Liu and co-workers were able to show that binding of eLtaS to insulin resulted in insulin being unable to interact with the insulin receptor.

Next, Liu and colleagues created eLtaS transgenic C57BL/6J mice (eLtaStrans), which expressed eLtaS without being infected with S. aureus and had higher serum levels of triglycerides than wild-type controls. Postprandial hyperglycaemia, which is often associated with the development of type 2 diabetes mellitus and its complications, was higher in the eLtaStrans mice than in the control mice, indicating that the transgenic mice had impaired glucose tolerance.

Finally, the researchers developed a human monoclonal antibody against eLtaS (YG2). Administration of YG2 to the transgenic mice or mice challenged with S. aureus restored glucose tolerance. “Our findings reveal that S. aureus infection is a risk factor for insulin resistance and provide a potential mechanism underlying insulin resistance,” write the authors.