A bacterial effector manipulates host lysosomal protease activity-dependent plasticity in cell death modalities to facilitate infection

Crosstalk between cell death programs confers appropriate host anti-infection immune responses, but how pathogens co-opt host molecular switches of cell death pathways to reprogram cell death modalities for facilitating infection remains largely unclear. Here, we identify mammalian cell entry 3C (Mce3C) as a pathogenic cell death regulator secreted by Mycobacterium tuberculosis (Mtb), which causes tuberculosis featuring lung inflammation and necrosis. Mce3C binds host cathepsin B (CTSB), a non-caspase protease acting as a lysosome-derived molecular determinant of cell death modalities, to inhibit its protease activity towards BH3-interacting domain death agonist (BID) and receptor-interacting protein kinase 1 (RIPK1), thereby preventing the production of pro-apoptotic truncated BID (tBID) while maintaining the abundance of pro-necroptotic RIPK1. Disrupting the Mce3C-CTSB interaction promotes host apoptosis while suppressing necroptosis with attenuated Mtb survival and mitigated lung imm..., , , # **A bacterial effector manipulates host lysosomal protease activity-dependent plasticity in cell death modalities to facilitate infection**

[https://doi.org/10.5061/dryad.hmgqnk9qg](https://doi.org/10.5061/dryad.hmgqnk9qg)

This dataset is the source data of the main figures in the paper titled “A bacterial effector manipulates host lysosomal protease activity-dependent plasticity in cell death modalities to facilitate infection”, which is expected to be published in *PNAS* (Proceedings of the National Academy of Sciences) ([https://doi.org/10.1073/pnas.2406715122](https://doi.org/10.1073/pnas.2406715122)).

All other source images (including unprocessed immunoblots, immunofluorescence staining, H&E staining, etc.), source movies, as well as source data underlying the supplementary figures of the aforementioned paper, can be obtained from figshare ([https://doi.org/10.6084/m9.figshare.28327367](https://doi.org/10.6084/m9.figshare.28327367)).

If this dataset is used for a publica...