Metallochaperones Are Needed for Mycobacterium tuberculosis and Escherichia coli Nicotinamidase-Pyrazinamidase Activity

Author:

Sheen Patricia1,Monsalve Anuntxi1,Campos Jhanina1,Huerta Rodolfo1,Antiparra Ricardo1,Arteaga Héctor1,Duran Patricia1,Bueno Carlos1,Kirwan Daniela E.2,Gilman Robert H.3,Zimic Mirko1

Affiliation:

1. Laboratory of Bioinformatics and Molecular Biology, Department of Cellular and Molecular Sciences, School of Science, Universidad Peruana Cayetano Heredia, Lima, Peru

2. Infection and Immunity Research Institute, St. George’s, University of London, London, United Kingdom

3. Department of International Health, School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA

Abstract

Tuberculosis is an infectious disease caused by the bacterium Mycobacterium tuberculosis and remains one of the major causes of disease and death worldwide. Pyrazinamide is a key drug used in the treatment of tuberculosis, yet its mechanism of action is not fully understood, and testing strains of M. tuberculosis for pyrazinamide resistance is not easy with the tools that are presently available. The significance of the present research is that a metallochaperone-like protein may be crucial to pyrazinamide’s mechanisms of action and of resistance. This may support the development of improved tools to detect pyrazinamide resistance, which would have significant implications for the clinical management of patients with tuberculosis: drug regimens that are appropriately tailored to the resistance profile of a patient’s individual strain lead to better clinical outcomes, reduced onward transmission of infection, and reduction of the development of resistant strains that are more challenging and expensive to treat.

Funder

Wellcome Trust

Publisher

American Society for Microbiology

Subject

Molecular Biology,Microbiology

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