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Nat Microbiol. 2018 May;3(5):622-631. doi: 10.1038/s41564-018-0146-2. Epub 2018 Apr 16.

The extracellular domain of Staphylococcus aureus LtaS binds insulin and induces insulin resistance during infection.

Liu Y1,2, Liu FJ1,2, Guan ZC1,2, Dong FT3, Cheng JH3, Gao YP1,2, Li D1,2, Yan J1,2, Liu CH1,2, Han DP1,2, Ma CM4, Feng JN1,2, Shen BF1,2, Yang G5,6.

Author information

1
Beijing Institute of Basic Medical Sciences, Beijing, China.
2
State Key Laboratory of Toxicology and Medical Countermeasures, Beijing, China.
3
National Center of Biomedical Analysis, Beijing, China.
4
Health Care Center, Hospital of Chinese People's Armed Police Force, Beijing, China.
5
Beijing Institute of Basic Medical Sciences, Beijing, China. yangg62033@outlook.com.
6
State Key Laboratory of Toxicology and Medical Countermeasures, Beijing, China. yangg62033@outlook.com.

Abstract

Insulin resistance is a risk factor for obesity and diabetes and predisposes individuals to Staphylococcus aureus colonization; however, the contribution of S. aureus to insulin resistance remains unclear. Here, we show that S. aureus infection causes impaired glucose tolerance via secretion of an insulin-binding protein extracellular domain of LtaS, eLtaS, which blocks insulin-mediated glucose uptake. Notably, eLtaS transgenic mice (eLtaS trans ) exhibited a metabolic syndrome similar to that observed in patients, including increased food and water consumption, impaired glucose tolerance and decreased hepatic glycogen synthesis. Furthermore, transgenic mice showed significant metabolic differences compared to their wild-type counterparts, particularly for the early insulin resistance marker α-hydroxybutyrate. We subsequently developed a full human monoclonal antibody against eLtaS that blocked the interaction between eLtaS and insulin, which effectively restored glucose tolerance in eLtaS trans and S. aureus-challenged mice. Thus, our results reveal a mechanism for S. aureus-induced insulin resistance.

PMID:
29662128
DOI:
10.1038/s41564-018-0146-2

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