A hydrolase of trehalose dimycolate induces nutrient influx and stress sensitivity to balance intracellular growth of Mycobacterium tuberculosis.
Identifieur interne : 004297 ( Main/Exploration ); précédent : 004296; suivant : 004298A hydrolase of trehalose dimycolate induces nutrient influx and stress sensitivity to balance intracellular growth of Mycobacterium tuberculosis.
Auteurs : Yong Yang [États-Unis] ; Kathleen Kulka [États-Unis] ; Ronald C. Montelaro [États-Unis] ; Todd A. Reinhart [États-Unis] ; James Sissons [États-Unis] ; Alan Aderem [États-Unis] ; Anil K. Ojha [États-Unis]Source :
- Cell host & microbe [ 1934-6069 ] ; 2014.
Descripteurs français
- KwdFr :
- Animaux, Cytosol (microbiologie), Délétion de gène, Facteurs cord (métabolisme), Hydrolases (génétique), Hydrolases (métabolisme), Hydrolyse, Mycobacterium tuberculosis (croissance et développement), Mycobacterium tuberculosis (enzymologie), Mycobacterium tuberculosis (génétique), Mycobacterium tuberculosis (physiologie), Souris, Souris knockout.
- MESH :
- croissance et développement : Mycobacterium tuberculosis.
- enzymologie : Mycobacterium tuberculosis.
- génétique : Hydrolases, Mycobacterium tuberculosis.
- microbiologie : Cytosol.
- métabolisme : Facteurs cord, Hydrolases.
- physiologie : Mycobacterium tuberculosis.
- Animaux, Délétion de gène, Hydrolyse, Souris, Souris knockout.
English descriptors
- KwdEn :
- Animals, Cord Factors (metabolism), Cytosol (microbiology), Gene Deletion, Hydrolases (genetics), Hydrolases (metabolism), Hydrolysis, Mice, Mice, Knockout, Mycobacterium tuberculosis (enzymology), Mycobacterium tuberculosis (genetics), Mycobacterium tuberculosis (growth & development), Mycobacterium tuberculosis (physiology).
- MESH :
- chemical , genetics : Hydrolases.
- chemical , metabolism : Cord Factors, Hydrolases.
- enzymology : Mycobacterium tuberculosis.
- genetics : Mycobacterium tuberculosis.
- growth & development : Mycobacterium tuberculosis.
- microbiology : Cytosol.
- physiology : Mycobacterium tuberculosis.
- Animals, Gene Deletion, Hydrolysis, Mice, Mice, Knockout.
Abstract
Chronic tuberculosis in an immunocompetent host is a consequence of the delicately balanced growth of Mycobacterium tuberculosis (Mtb) in the face of host defense mechanisms. We identify an Mtb enzyme (TdmhMtb) that hydrolyzes the mycobacterial glycolipid trehalose dimycolate and plays a critical role in balancing the intracellular growth of the pathogen. TdmhMtb is induced under nutrient-limiting conditions and remodels the Mtb envelope to increase nutrient influx but concomitantly sensitizes Mtb to stresses encountered in the host. Consistent with this, a ΔtdmhMtb mutant is more resilient to stress and grows to levels higher than those of wild-type in immunocompetent mice. By contrast, mutant growth is retarded in MyD88(-/-) mice, indicating that TdmhMtb provides a growth advantage to intracellular Mtb in an immunocompromised host. Thus, the effects and countereffects of TdmhMtb play an important role in balancing intracellular growth of Mtb in a manner that is directly responsive to host innate immunity.
DOI: 10.1016/j.chom.2014.01.008
PubMed: 24528862
Affiliations:
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Ojha</name><affiliation wicri:level="4"><nlm:affiliation>Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, PA 15261, USA. 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We identify an Mtb enzyme (TdmhMtb) that hydrolyzes the mycobacterial glycolipid trehalose dimycolate and plays a critical role in balancing the intracellular growth of the pathogen. TdmhMtb is induced under nutrient-limiting conditions and remodels the Mtb envelope to increase nutrient influx but concomitantly sensitizes Mtb to stresses encountered in the host. Consistent with this, a ΔtdmhMtb mutant is more resilient to stress and grows to levels higher than those of wild-type in immunocompetent mice. By contrast, mutant growth is retarded in MyD88(-/-) mice, indicating that TdmhMtb provides a growth advantage to intracellular Mtb in an immunocompromised host. Thus, the effects and countereffects of TdmhMtb play an important role in balancing intracellular growth of Mtb in a manner that is directly responsive to host innate immunity.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Pennsylvanie</li><li>Washington (État)</li></region><settlement><li>Pittsburgh</li></settlement><orgName><li>Université de Pittsburgh</li></orgName></list><tree><country name="États-Unis"><region name="Pennsylvanie"><name sortKey="Yang, Yong" sort="Yang, Yong" uniqKey="Yang Y" first="Yong" last="Yang">Yong Yang</name></region><name sortKey="Aderem, Alan" sort="Aderem, Alan" uniqKey="Aderem A" first="Alan" last="Aderem">Alan Aderem</name><name sortKey="Kulka, Kathleen" sort="Kulka, Kathleen" uniqKey="Kulka K" first="Kathleen" last="Kulka">Kathleen Kulka</name><name sortKey="Montelaro, Ronald C" sort="Montelaro, Ronald C" uniqKey="Montelaro R" first="Ronald C" last="Montelaro">Ronald C. Montelaro</name><name sortKey="Ojha, Anil K" sort="Ojha, Anil K" uniqKey="Ojha A" first="Anil K" last="Ojha">Anil K. Ojha</name><name sortKey="Reinhart, Todd A" sort="Reinhart, Todd A" uniqKey="Reinhart T" first="Todd A" last="Reinhart">Todd A. Reinhart</name><name sortKey="Sissons, James" sort="Sissons, James" uniqKey="Sissons J" first="James" last="Sissons">James Sissons</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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