Mycobacterium Tuberculosis Exploits Asparagine to Assimilate Nitrogen and Resist Acid Stress During Infection

Overview

Journal PLoS Pathog

Specialty Microbiology

Date 2014 Mar 4

PMID 24586151

Citations 93

Authors

Alexandre Gouzy

Gerald Larrouy-Maumus

Daria Bottai

Florence Levillain

Alexia Dumas

Joshua B Wallach

Irene Caire-Brandli

Chantal de Chastellier

Ting-Di Wu

Renaud Poincloux

Roland Brosch

Jean-Luc Guerquin-Kern

Dirk Schnappinger

Luiz Pedro Sorio de Carvalho

Yannick Poquet

Olivier Neyrolles

Affiliations

Soon will be listed here.

Abstract

Mycobacterium tuberculosis is an intracellular pathogen. Within macrophages, M. tuberculosis thrives in a specialized membrane-bound vacuole, the phagosome, whose pH is slightly acidic, and where access to nutrients is limited. Understanding how the bacillus extracts and incorporates nutrients from its host may help develop novel strategies to combat tuberculosis. Here we show that M. tuberculosis employs the asparagine transporter AnsP2 and the secreted asparaginase AnsA to assimilate nitrogen and resist acid stress through asparagine hydrolysis and ammonia release. While the role of AnsP2 is partially spared by yet to be identified transporter(s), that of AnsA is crucial in both phagosome acidification arrest and intracellular replication, as an M. tuberculosis mutant lacking this asparaginase is ultimately attenuated in macrophages and in mice. Our study provides yet another example of the intimate link between physiology and virulence in the tubercle bacillus, and identifies a novel pathway to be targeted for therapeutic purposes.

Citing Articles

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