Physiology of antibiotics lethality in Mycobacteria

• Main Author: Jin, Frances Xin Er
• Other Authors: Kevin Pethe
• Format: Final Year Project
• Language: English
• Published: 2016
• Subjects: DRNTU::Science::Biological sciences::Microbiology::Drug Resistance
• Online Access: http://hdl.handle.net/10356/67197
• Institution: Nanyang Technological University

The increasing prevalence and spread of drug-resistant strains of M.tuberculosis has resulted in the rise of MDR-TB and XDR-TB cases around the world. This necessitates the need for a better understanding of current bactericidal antibiotics mode of action so as to increase efficacy of current treatment regimens and uncover novel drug targets. Here we showed that bactericidal antibiotics mode of action induces a death signature involving cellular metabolism. We demonstrated that co-treatment with respiratory inhibitors such as Carbonyl Cyanide m-chlorophenylhydrazone (CCCP) can exert a rescue effect on the killing mechanism of bactericidal antibiotics. Our results suggest that the presence of the death signature is common for at least two different classes of bactericidal antibiotics, and that there is downstream involvement of cellular metabolism processes such as respiration in antibiotics bactericidal mechanism.