Mycobacterium tuberculosis exploits asparagine to assimilate nitrogen and resist acid stress during infection.
PLoS Pathog
; 10(2): e1003928, 2014 Feb.
Article
em En
| MEDLINE
| ID: mdl-24586151
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.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
2_ODS3
Base de dados:
MEDLINE
Assunto principal:
Asparagina
/
Estresse Fisiológico
/
Tuberculose
/
Fagossomos
/
Macrófagos
/
Mycobacterium tuberculosis
/
Nitrogênio
Limite:
Animals
Idioma:
En
Revista:
PLoS Pathog
Ano de publicação:
2014
Tipo de documento:
Article