senX3-independent contribution of regX3 to Mycobacterium tuberculosis virulence

BMC Microbiology

Petros C Karakousis³  Deborah A Belchis¹  Dalin Rifat² 

[1] Department of Pathology, Johns Hopkins University School of Medicine, Baltimore 21287, MD, USA;Department of Medicine, Johns Hopkins University School of Medicine, Center for Tuberculosis Research, 1551 East Jefferson Street, Room 110, Baltimore 21287, MD, USA;Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore 21205, MD, USA

关键词: Cross-regulation;    Mouse;    Starvation;    Nutrient;    Phosphate;    Virulence;    Persistence;    Stringent response;    Specificity;    Mycobacterium tuberculosis;   

Others  :  1137744
DOI  :  10.1186/s12866-014-0265-8

 received in 2014-07-10, accepted in 2014-10-09,  发布年份 2014

【 摘 要 】

Background

Mycobacterium tuberculosis (Mtb) must adapt to various stress conditions during host infection. The two-component regulatory system (2CRS) SenX3-RegX3 is required for Mtb virulence. We showed recently that the senX3-regX3 intergenic region contains promoter activity, driving senX3-independent regX3 expression. In the current study, we tested the hypothesis that RegX3 has a SenX3-independent role in Mtb virulence. The gene expression patterns, growth, and survival of mutants containing transposon insertions in senX3 (senX3::Tn) and regX3 (regX3::Tn) were compared to those of their respective complemented strains and the isogenic wild-type parent strain during axenic growth in nutrient-rich broth, phosphate depletion, nutrient starvation, and in the lungs of BALB/c mice.

Results

regX3 expression was reduced in senX3::Tn during phosphate depletion and nutrient starvation, and expression of the phosphate-specific transport gene pstC2 was reduced similarly in senX3::Tn and regX3::Tn during phosphate depletion. Although senX3 and regX3 were each dispensable for Mtb growth in nutrient-rich broth, disruption of senX3 or regX3 caused a similar growth defect during phosphate depletion. Interestingly, senX3::Tn, in which monocistronic regX3 expression is preserved, showed significantly higher survival relative to regX3::Tn after 7 days of nutrient starvation (p <0.01), and in mouse lungs at Day 31 (p < 0.01), Day 62 (p < 0.01), and Day 124 (p = 0.05) after aerosol infection.

Conclusion

Our data demonstrate the specificity of the senX3-regX3 2CRS for sensing and responding to low ambient phosphate, but also raise the possibility that RegX3 may function independently of its cognate sensor histidine kinase.

【 授权许可】

   
2014 Rifat et al.; licensee BioMed Central Ltd.

【 图 表 】

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