Authors
Yingying Lu, Jie Liu, Chengyu Liu, Zehua Zuo, Michael Ewing, Hang Chen, Toren Finkel, Stephen H Leppla, Shihui Liu
Published in
PLoS biology. Volume 24. Issue 8. Pages e3003957. Aug 21, 2026. Epub Aug 21, 2026.
Abstract
Hemolysin BL (HBL) is a tripartite α‑pore‑forming toxin and a major Bacillus cereus virulence factor. Although LITAF and its homolog CDIP1 were previously identified as host receptors that promote HBL‑induced cytolysis, mice lacking both proteins remain only partially protected, indicating the existence of additional determinants of susceptibility. Using genome‑wide CRISPR knockout screens in Litaf-/-/Cdip1-/- mouse embryonic fibroblasts and human HT1080 cells, we identify caveolin‑1 (CAV1), a caveola‑associated membrane protein, as a third conserved host factor required for HBL cytolytic activity. Confocal imaging and co‑immunoprecipitation analyses show that CAV1 colocalizes with HBL and physically associates with the toxin at the plasma membrane. Notably, mice lacking all three factors (Litaf/Cdip1/Cav1 triple knockouts) are completely resistant to HBL toxin challenge, establishing CAV1 as an additional host factor mediating HBL toxin cytotoxicity. These findings define a tripartite host factor system required for HBL toxin activity and position CAV1 as an additional host determinant to B. cereus virulence.
PMID:
42627856
Bibliographic data and abstract were imported from PubMed on 22 Aug 2026.
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