Guanylate-Binding Protein 1 Regulates Infection-Induced Autophagy through TBK1 Phosphorylation

Invading bacteria can be degraded by selective autophagy, known as xenophagy. Recent studies have shown that the recruitment of autophagy adaptor proteins such p62 to and its regulation activated TANK-binding kinase 1 (TBK1) are required overcome bacterial infection. However, detailed molecular mechanisms behind this not yet fully understood. Here, we show human guanylate-binding protein (GBP) family, especially GBP1, directs xenophagy against invading Group A Streptococcus (GAS) promoting TBK1 phosphorylation. GBP1 exhibits a GAS-surrounding localization response bacterially caused membrane damage mediated sensor galectin-3. We found knockout attenuated activation, followed reduced lower bactericidal activity Furthermore, GBP1-TBK1 interaction was detected immunoprecipitation. Our findings collectively indicate contributes GAS-targeted initiated detection galectin-3 via