期刊论文详细信息
Frontiers in Cellular and Infection Microbiology 卷:7
Overexpression of Adenylyl Cyclase Encoded by the Mycobacterium tuberculosis Rv2212 Gene Confers Improved Fitness, Accelerated Recovery from Dormancy and Enhanced Virulence in Mice
Arseny S. Kaprelyants1  Tatyana K. Kondratieva1  Elvira I. Rubakova1  Alexander S. Apt2  Margarita O. Shleeva3  Anna V. Goncharenko3  Galina R. Demina3 
[1] Department of Immunology, Laboratory for Immunogenetics, Central Institute for TuberculosisMoscow, Russia;
[2] Department of Immunology, School of Biology, Lomonosov Moscow State UniversityMoscow, Russia;
[3] Federal Research Centre ‘Fundamentals of Biotechnology’ of the Russian Academy of Sciences, A. N. Bach Institute of BiochemistryMoscow, Russia;
关键词: Mycobacterium tuberculosis;    cAMP;    adenylyl cyclase;    Rv2212;    dormant mycobacteria;   
DOI  :  10.3389/fcimb.2017.00370
来源: DOAJ
【 摘 要 】

Earlier we demonstrated that the adenylyl cyclase (AC) encoded by the MSMEG_4279 gene plays a key role in the resuscitation and growth of dormant Mycobacterium smegmatis and that overexpression of this gene leads to an increase in intracellular cAMP concentration and prevents the transition of M. smegmatis from active growth to dormancy in an extended stationary phase accompanied by medium acidification. We surmised that the homologous Rv2212 gene of M. tuberculosis (Mtb), the main cAMP producer, plays similar physiological roles by supporting, under these conditions, the active state and reactivation of dormant bacteria. To test this hypothesis, we established Mtb strain overexpressing Rv2212 and compared its in vitro and in vivo growth characteristics with a control strain. In vitro, the AC-overexpressing pMindRv2212 strain demonstrated faster growth in a liquid medium, prolonged capacity to form CFUs and a significant delay or even prevention of transition toward dormancy. AC-overexpressing cells exhibited easier recovery from dormancy. In vivo, AC-overexpressing bacteria demonstrated significantly higher growth rates (virulence) in the lungs and spleens of infected mice compared to the control strain, and, unlike the latter, killed mice in the TB-resistant strain before month 8 of infection. Even in the absence of selecting hygromycin B, all pMindRv2212 CFUs retained the Rv2212 insert during in vivo growth, strongly suggesting that AC overexpression is beneficial for bacteria. Taken together, our results indicate that cAMP supports the maintenance of Mtb cells vitality under unfavorable conditions in vitro and their virulence in vivo.

【 授权许可】

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