Models of nonreplication help us understand the biology of persistent Mycobacterium tuberculosis. High throughput screening (HTS) against nonreplicating M. tuberculosis may lead to identification of tool compounds that affect pathways on which bacterial survival depends in such states and to development of drugs that can overcome phenotypic resistance to conventional…
Antimicrobial susceptibility testing is the mainstay of tuberculosis drug development programs. In this chapter, we describe methods for determination of the minimum inhibitory concentration of compounds against Mycobacterium tuberculosis growing in liquid media as a function of carbon source, detergent, and environmental stress imposed by acidic pH as well as…
Human tuberculosis (TB) is primarily caused by Mycobacterium tuberculosis (Mtb) that inhabits inside and amidst immune cells of the host with adapted physiology to regulate interdependent cellular functions with intact pathogenic potential. The complexity of this disease is attributed to various factors such as the reactivation of latent TB form…
Tuberculosis (TB) is a communicable airborne infectious disease caused by the Mycobacterium tuberculosis (MTB) that primarily affects the lungs, and can disseminate to other parts of the body. MTB is one of the most dangerous pathogens, killing about 1.4 million people annually worldwide. Although the standard treatment of TB is…
: We characterized BCG isolates found in lung and brain samples from a previously vaccinated patient with IFNγR1 deficiency. The isolates collected displayed distinct genomic and phenotypic features consistent with host adaptation and associated changes in antibiotic susceptibility and virulence traits. : We report a case of a patient with…
Screening of a diversity-oriented compound library led to the identification of two 6,11-dioxobenzo[]pyrido[1,2-]indoles (DBPI) that displayed low micromolar bactericidal activity against the Erdman strain of . The activity of these hit compounds was limited to tubercle bacilli, including the nonreplicating form, and to . On hit expansion and investigation of…
Diphenyl ether derivatives inhibit mycobacterial cell wall synthesis by inhibiting an enzyme, enoyl-acyl carrier protein reductase (InhA), which catalyses the last step in the fatty acid synthesis cycle of genus Mycobacterium. To select and validate a protein crystal structure of enoyl-acyl carrier protein reductase of Mycobacterium tuberculosis for designing inhibitors…
