| First Author | Liu J | Year | 2020 |
| Journal | Cell Host Microbe | Volume | 28 |
| Issue | 3 | Pages | 402-410.e5 |
| PubMed ID | 32544461 | Mgi Jnum | J:321867 |
| Mgi Id | MGI:6871740 | Doi | 10.1016/j.chom.2020.05.012 |
| Citation | Liu J, et al. (2020) Sequential CRISPR-Based Screens Identify LITAF and CDIP1 as the Bacillus cereus Hemolysin BL Toxin Host Receptors. Cell Host Microbe 28(3):402-410.e5 |
| abstractText | Bacteria and their toxins are associated with significant human morbidity and mortality. While a few bacterial toxins are well characterized, the mechanism of action for most toxins has not been elucidated, thereby limiting therapeutic advances. One such example is the highly potent pore-forming toxin, hemolysin BL (HBL), produced by the gram-positive pathogen Bacillus cereus. However, how HBL exerts its effects and whether it requires any host factors is unknown. Here, we describe an unbiased genome-wide CRISPR-Cas9 knockout screen that identified LPS-induced TNF-alpha factor (LITAF) as the HBL receptor. Using LITAF-deficient cells, a second, subsequent whole-genome CRISPR-Cas9 screen identified the LITAF-like protein CDIP1 as a second, alternative receptor. We generated LITAF-deficient mice, which exhibit marked resistance to lethal HBL challenges. This work outlines and validates an approach to use iterative genome-wide CRISPR-Cas9 screens to identify the complement of host factors exploited by bacterial toxins to exert their myriad biological effects. |
