The MmpS6-MmpL6 Operon Is an Oxidative Stress Response System Providing Selective Advantage to Mycobacterium tuberculosis in Stress.
Bacterial Proteins
/ genetics
Gene Expression Regulation, Bacterial
/ drug effects
Humans
Macrophages
/ microbiology
Mycobacterium tuberculosis
/ drug effects
Naphthoquinones
/ pharmacology
Operon
/ genetics
Oxidation-Reduction
/ drug effects
Oxidative Stress
/ drug effects
Reactive Oxygen Species
THP-1 Cells
Triclosan
/ pharmacology
Journal
The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675
Informations de publication
Date de publication:
09 01 2019
09 01 2019
Historique:
received:
25
05
2018
accepted:
30
08
2018
pubmed:
12
9
2018
medline:
13
11
2019
entrez:
12
9
2018
Statut:
ppublish
Résumé
The stress response adaptability of Mycobacterium tuberculosis (Mtb) is still unresolved. In this study, we ascribe an important function to the MmpS6-MmpL6 (M6) operon in Mtb stress management. By using a novel promoter probe in a high-throughput unbiased screen, we identified several quinones as potent inducers of the M6 operon in addition to triclosan. Triclosan and plumbagin effectively altered the intracellular redox potential in Mtb suggestive of oxidative stress in bacteria. Presence of the functional M6 operon correlated with an enhanced ability of clinical strains to survive in the presence of triclosan. Similar to the addition of a powerful reactive oxygen species-quenching agent such as N-acetyl cysteine in the medium, introduction of the complete M6 operon was sufficient to increase tolerance of the M6- strains to triclosan and plumbagin by effectively ablating the change in intracellular redox potential of Mtb, signifying the importance of this operon in oxidative stress survival in mycobacteria.
Sections du résumé
Background
The stress response adaptability of Mycobacterium tuberculosis (Mtb) is still unresolved. In this study, we ascribe an important function to the MmpS6-MmpL6 (M6) operon in Mtb stress management.
Methods
By using a novel promoter probe in a high-throughput unbiased screen, we identified several quinones as potent inducers of the M6 operon in addition to triclosan.
Results
Triclosan and plumbagin effectively altered the intracellular redox potential in Mtb suggestive of oxidative stress in bacteria. Presence of the functional M6 operon correlated with an enhanced ability of clinical strains to survive in the presence of triclosan.
Conclusions
Similar to the addition of a powerful reactive oxygen species-quenching agent such as N-acetyl cysteine in the medium, introduction of the complete M6 operon was sufficient to increase tolerance of the M6- strains to triclosan and plumbagin by effectively ablating the change in intracellular redox potential of Mtb, signifying the importance of this operon in oxidative stress survival in mycobacteria.
Identifiants
pubmed: 30203030
pii: 5092676
doi: 10.1093/infdis/jiy526
doi:
Substances chimiques
Bacterial Proteins
0
Naphthoquinones
0
Reactive Oxygen Species
0
Triclosan
4NM5039Y5X
plumbagin
YAS4TBQ4OQ
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM