The adenylyl cyclase Rv2212 modifies the proteome and infectivity of Mycobacterium bovis BCG
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
- MeSH
- adenylátcyklasy genetika metabolismus MeSH
- bakteriální proteiny genetika metabolismus MeSH
- buněčné linie MeSH
- chaperon hsp60 genetika metabolismus MeSH
- lidé MeSH
- makrofágy mikrobiologie MeSH
- Mycobacterium bovis genetika metabolismus patogenita MeSH
- Mycobacterium tuberculosis enzymologie genetika patogenita MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- plíce mikrobiologie MeSH
- proteom genetika metabolismus MeSH
- slezina mikrobiologie MeSH
- tuberkulóza mikrobiologie MeSH
- virulence MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- adenylátcyklasy MeSH
- bakteriální proteiny MeSH
- chaperon hsp60 MeSH
- proteom MeSH
All organisms have the capacity to sense and respond to environmental changes. These signals often involve the use of second messengers such as cyclic adenosine monophosphate (cAMP). This second messenger is widely distributed among organisms and coordinates gene expression related with pathogenesis, virulence, and environmental adaptation. Genomic analysis in Mycobacterium tuberculosis has identified 16 adenylyl cyclases (AC) and one phosphodiesterase, which produce and degrade cAMP, respectively. To date, ten AC have been biochemically characterized and only one (Rv0386) has been found to be important during murine infection with M. tuberculosis. Here, we investigated the impact of hsp60-driven Rv2212 gene expression in Mycobacterium bovis Bacillus Calmette-Guerin (BCG) during growth in vitro, and during macrophage and mice infection. We found that hsp60-driven expression of Rv2212 resulted in an increased capacity of replication in murine macrophages but an attenuated phenotype in lungs and spleen when administered intravenously in mice. Furthermore, this strain displayed an altered proteome mainly affecting proteins associated with stress conditions (bfrB, groEL-2, DnaK) that could contribute to the attenuated phenotype observed in mice.
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