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1.B.164.  The Mycobacterial Outer Membrane Calcium Channel (CpnT) Family 

CpnT has a dual function in uptake of nutrients including Ca2+ and induction of host cell death. The N-terminal domain (NTD) forms an outer membrane channel and is used for uptake of nutrients across the outer membrane. The secreted C-terminal toxic domain (TNT) acts as a glycohydrolase, which hydrolyzes the essential cellular coenzyme NAD+ in the cytosol of infected macrophages, leading to necrotic host cell death. Both functions are required for survival, replication and cytotoxicity of M. tuberculosis in macrophages (Danilchanka et al. 2014; Sun et al. 2015).  This pathogen relies upon CpnT for the development of multidrug resistance via gene mutation and the evolutionary development of new calcium channels (D'Elia and Weinrauch 2023).

References associated with 1.B.164 family:

D'Elia, J.A. and L.A. Weinrauch. (2023). Gated Calcium Ion Channel and Mutation Mechanisms in Multidrug-Resistant Tuberculosis. Int J Mol Sci 24:. 37298620
Danilchanka, O., J. Sun, M. Pavlenok, C. Maueröder, A. Speer, A. Siroy, J. Marrero, C. Trujillo, D.L. Mayhew, K.S. Doornbos, L.E. Muñoz, M. Herrmann, S. Ehrt, C. Berens, and M. Niederweis. (2014). An outer membrane channel protein of Mycobacterium tuberculosis with exotoxin activity. Proc. Natl. Acad. Sci. USA 111: 6750-6755. 24753609
Sun, J., A. Siroy, R.K. Lokareddy, A. Speer, K.S. Doornbos, G. Cingolani, and M. Niederweis. (2015). The tuberculosis necrotizing toxin kills macrophages by hydrolyzing NAD. Nat Struct Mol Biol 22: 672-678. 26237511