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).