التفاصيل البيبلوغرافية
| العنوان: |
Multiple genetic paths including massive gene amplification allow Mycobacterium tuberculosis to overcome loss of ESX-3 secretion system substrates. |
| المؤلفون: |
Lin Wang, Asare, Emmanuel, Shetty, Amol C., Sanchez-Tumbaco, Freddy, Edwards, Megan R., Saranathan, Rajagopalan, Weinrick, Brian, Jiayong Xu, Bing Chen, Bénard, Angèle, Dougan, Gordon, Leung, Daisy W., Amarasinghe, Gaya K., Chan, John, Basler, Christopher F., Jacobs, William R., Tufariello, JoAnn M. |
| المصدر: |
Proceedings of the National Academy of Sciences of the United States of America; 2/22/2022, Vol. 119 Issue 8, p1-12, 12p |
| مصطلحات موضوعية: |
MYCOBACTERIUM tuberculosis, GENE amplification, SECRETION, IRON, CHROMOSOMES |
| مستخلص: |
Mycobacterium tuberculosis (Mtb) possesses five type VII secretion systems (T7SS), virulence determinants that include the secretion apparatus and associated secretion substrates. Mtb strains deleted for the genes encoding substrates of the ESX-3 T7SS, esxG or esxH, require iron supplementation for in vitro growth and are highly attenuated in vivo. In a subset of infected mice, suppressor mutants of esxG or esxH deletions were isolated, which enabled growth to high titers or restored virulence. Suppression was conferred by mechanisms that cause overexpression of an ESX-3 paralogous region that lacks genes for the secretion apparatus but encodes EsxR and EsxS, apparent ESX-3 orphan substrates that functionally compensate for the lack of EsxG or EsxH. The mechanisms include the disruption of a transcriptional repressor and a massive 38- to 60-fold gene amplification. These data identify an iron acquisition regulon, provide insight into T7SS, and reveal a mechanism of Mtb chromosome evolution involving “accordion-type” amplification. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
