info:eu-repo/semantics/article
New Conjugated Compound T5 Epidioxy-Sterol-ANB Inhibits the Growth of Mycobacterium tuberculosis Affecting the Cholesterol and Folate Pathways
Registro en:
Baena A, Vasco E, Pastrana M, Alzate JF, Barrera LF and Martínez A (2020) New Conjugated Compound T5 Epidioxy-Sterol-ANB Inhibits the Growth of Mycobacterium tuberculosis Affecting the Cholesterol and Folate Pathways. Front. Microbiol. 11:537935. doi: 10.3389/fmicb.2020.537935
1664-302X
10.3389/fmicb.2020.537935
Autor
Baena García, Andrés
Vasco Pérez, Emanuel
Pastrana Restrepo, Manuel Humberto
Alzate Restrepo, Juan Fernando
Barrera Robledo, Luis Fernando
Martínez Martínez, Alejandro
Institución
Resumen
ABSTRACT: The upsurge and persistence of drug resistant strains of Mycobacterium tuberculosis
(Mtb) is an important limitant to the battery of drugs available for the elimination of
tuberculosis (TB). To avoid future scarcity of antibiotics against Mtb, it is important to
discover new effective anti-mycobacterial agents. In this study, we present data from a
series of experiments to determine in vitro and in vivo anti-mycobacterial activity of a
library of epidioxy-sterol analogs. We test 15 compounds for their ability to reduce the
viability of Mtb. We found that one compound called T5 epidioxy-sterol-ANB display
significant potency against Mtb in vitro specifically inside macrophages but without
effectivity in axenic cultures. A viability assay confirms that this T5 compound is less
toxic for macrophages in vitro as compared to the current Mtb drug Rifampicin at higher
concentrations. We use a transcriptomic analysis of Mtb inside macrophages after T5
epidioxy-sterol-ANB treatment, and we found a significant down-regulation of enzymes
involved in the cholesterol and folic acid pathways. In vivo, significant differences were
found in the lungs and spleen CFUs of Mtb infected mice treated with the T5 epidioxysterol-ANB as compared with the untreated control group, which provides additional
evidence of the effectivity of the T5 compound. Altogether these results confirm the
potential of this T5 epidioxy-sterol-ANB compound against Mtb.