AUTHOR=Meng Meiqi , Wang Jiachao , Li Hongru , Wang Jiao , Wang Xuan , Li Miao , Gao Xue , Li Wenjian , Ma Cuiqing , Wei Lin 

TITLE=Eliminating the invading extracellular and intracellular FnBp+ bacteria from respiratory epithelial cells by autophagy mediated through FnBp-Fn-Integrin α5β1 axis

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=13

YEAR=2024

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2023.1324727

DOI=10.3389/fcimb.2023.1324727

ISSN=2235-2988

ABSTRACT=<sec><title>Background</title><p>We previously found that the respiratory epithelial cells could eliminate the invaded <italic>group A streptococcus</italic> (GAS) through autophagy induced by binding a fibronectin (Fn) binding protein (FnBp) expressed on the surface of GAS to plasma protein Fn and its receptor integrin α5β1 of epithelial cells. Is autophagy initiated by FnBp<sup>+</sup> bacteria via FnBp-Fn-Integrin α5β1 axis a common event in respiratory epithelial cells?</p></sec><sec><title>Methods</title><p>We chose <italic>Staphylococcus aureus</italic> (<italic>S. aureus/S. a</italic>) and <italic>Listeria monocytogenes</italic> (<italic>L. monocytogenes/L. m</italic>) as representatives of extracellular and intracellular FnBp<sup>+</sup> bacteria, respectively. The FnBp of them was purified and the protein function was confirmed by western blot, viable bacteria count, confocal and pull-down. The key molecule downstream of the action axis was detected by IP, mass spectrometry and bio-informatics analysis.</p></sec><sec><title>Results</title><p>We found that different FnBp from both <italic>S. aureus</italic> and <italic>L. monocytogenes</italic> could initiate autophagy through FnBp-Fn-integrin α5β1 axis and this could be considered a universal event, by which host tries to remove invading bacteria from epithelial cells. Importantly, we firstly reported that S100A8, as a key molecule downstream of integrin β1 chain, is highly expressed upon activation of integrin α5β1, which in turn up-regulates autophagy.</p></sec><sec><title>Conclusions</title><p>Various FnBp from FnBp<sup>+</sup> bacteria have the ability to initiate autophagy via FnBp-Fn-Integrin α5β1 axis to promote the removal of invading bacteria from epithelial cells in the presence of fewer invaders. S100A8 is a key molecule downstream of Integrin α5β1 in this autophagy pathway.</p></sec>