Search

Mitochondria are essential and highly dynamic organelles whose morphology is determined by a steady-state balance between fusion and fission. Mitochondrial morphology and function are tightly connected. Because they are involved in many important cellular processes, including energy production, cell-autonomous immunity, and apoptosis, mitochondria present an attractive target for pathogens. Here, we explore the relationship between host cell mitochondria and intracellular bacteria, with a focus on mitochondrial morphology and function, as well as apoptosis. Modulation of apoptosis can allow bacteria to establish their replicative niche or support bacterial dissemination. Furthermore, bacteria can manipulate mitochondrial morphology and function through secreted effector proteins and can also contribute to the establishment of a successful infection, e.g., by favoring access to nutrients and/or evasion of the immune system.

Tuberculosis (TB) is the most important zoonotic bacterial disease in nonhuman primates (NHP). The current diagnostic method, the intradermal palpebral tuberculin test, has serious shortcomings. We characterized antibody responses in NHP againstMycobacterium tuberculosisto identify immunodominant antigens and develop a rapid serodiagnostic test for TB. A total of 422 NHP were evaluated, including 243 rhesus (Macaca mulatta), 46 cynomolgus (Macaca fascicularis), and 133 African green (Cercopithecus aethiops sabaeus) monkeys at five collaborative centers. Of those, 50 monkeys of the three species were experimentally inoculated withM. tuberculosis. Antibody responses were monitored every 2 to 4 weeks for up to 8 months postinfection by MultiAntigen Print ImmunoAssay with a panel of 12 recombinant antigens. All of the infected monkeys produced antibodies at various levels and with different antigen recognition patterns. ESAT-6 and MPB83 were the most frequently recognized proteins during infection. A combination of selected antigens which detected antibodies in all of the infected monkeys was designed to develop the PrimaTB STAT-PAK assay by lateral-flow technology. Serological evaluation demonstrated high diagnostic sensitivity (90%) and specificity (99%). The highest rate of TB detection was achieved when the skin test was combined with the PrimaTB STAT-PAK kit. This novel immunoassay provides a simple, rapid, and accurate test for TB in NHP.