Mycobacterium are responsible for numerous infections in humans, including tuberculosis, leprosy, and non-tuberculosis mycobacterium (NTM) infections. M. tuberculosis (Mtb), the causative agent of tuberculosis, was responsible for 1.7 million deaths in 2016 alone. Mycobacteria have significant innate immunity to numerous common antibiotics, such as β-lactams, through the endogenous production of β-lactamase enzymes and their thick cell wall. These bacteria are also developing increasing levels of resistance to frontline antibiotics, isoniazid and rifampicin. Despite increasing antibiotic resistance, the discovery and development of new antibiotics remains stagnant. In an effort to identify novel antibiotic scaffolds, we screened small molecules with varying structural scaffolds for antibiotic activity against M. smegmatis. A novel scaffold was identified and commercially available derivatives based on this scaffold were assessed to develop a preliminary structure-activity relationship. Complete biological data, preliminary structure-activity relationship, and future directions will be presented.

Identification and evaluation of small molecules with antibiotic activity in Mycobacterium

2019 Spring National Meeting

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