A Role for Mycobacterium Tuberculosis Sigma Factor C in Copper Nutritional Immunity
| Autor: | Samantha L. Tucker, Martin I. Voskuil, Tuhina Gupta, Benjamin T Grosse-Siestrup, Frederick D. Quinn, Russell K. Karls, Shelly Helms |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Transcription Genetic Operon Mutant Mice SCID lcsh:Chemistry Sigma factor Transcriptional regulation Mycobacterium lcsh:QH301-705.5 Spectroscopy Virulence General Medicine Computer Science Applications Cell biology Phenotype tuberculosis Female Copper Sulfate 030106 microbiology Sigma Factor Biology nutritional immunity Catalysis Article Inorganic Chemistry 03 medical and health sciences Bacterial Proteins Animals Physical and Theoretical Chemistry Molecular Biology Gene Transcription factor sigma factor C (SigC) Microbial Viability PPE1 Gene Expression Profiling Organic Chemistry Immunity Biological Transport Gene Expression Regulation Bacterial Mycobacterium tuberculosis biology.organism_classification 030104 developmental biology lcsh:Biology (General) lcsh:QD1-999 copper Mutation nonribosomal peptide synthase |
| Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 2118, p 2118 (2021) International Journal of Molecular Sciences Volume 22 Issue 4 |
| ISSN: | 1661-6596 1422-0067 |
| Popis: | Sigma factor C (SigC) contributes to Mycobacterium tuberculosis virulence in various animal models, but the stress response coordinated by this transcription factor was undefined. The results presented here indicate that SigC prevents copper starvation. Whole genome expression studies demonstrate short-term (4-hour) induction of sigC, controlled from a tetracycline-inducible promoter, upregulates ctpB and genes in the nonribosomal peptide synthase (nrp) operon. These genes are expressed at higher levels after 48-hour sigC induction, but also elevated are genes encoding copper-responsive regulator RicR and RicR-regulated copper toxicity response operon genes rv0846–rv0850, suggesting prolonged sigC induction results in excessive copper uptake. No growth and global transcriptional differences are observed between a sigC null mutant relative to its parent strain in 7H9 medium. In a copper-deficient medium, however, growth of the sigC deletion strain lags the parent, and 40 genes (including those in the nrp operon) are differentially expressed. Copper supplementation reverses the growth defect and silences most transcriptional differences. Together, these data support SigC as a transcriptional regulator of copper acquisition when the metal is scarce. Attenuation of sigC mutants in severe combined immunodeficient mice is consistent with an inability to overcome innate host defenses that sequester copper ions to deprive invading microbes of this essential micronutrient. |
| Databáze: | OpenAIRE |
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