Academic Journal
Nonredundant functions of Mycobacterium tuberculosis chaperones promote survival under stress
| العنوان: | Nonredundant functions of Mycobacterium tuberculosis chaperones promote survival under stress |
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| المؤلفون: | Harnagel, Alexa, Lopez Quezada, Landys, Park, Sae Woong, Baranowski, Catherine, Kieser, Karen, Jiang, Xiuju, Roberts, Julia, Vaubourgeix, Julien, Yang, Amy, Nelson, Brock, Fay, Allison, Rubin, Eric, Ehrt, Sabine, Nathan, Carl, Lupoli, Tania J. |
| المساهمون: | Helen Hay Whitney Foundation, Bill and Melinda Gates Foundation, National Science Foundation, Simons Foundation, Center for Scientific Review |
| المصدر: | Molecular Microbiology ; volume 115, issue 2, page 272-289 ; ISSN 0950-382X 1365-2958 |
| بيانات النشر: | Wiley |
| سنة النشر: | 2020 |
| المجموعة: | Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: | Bacterial chaperones ClpB and DnaK, homologs of the respective eukaryotic heat shock proteins Hsp104 and Hsp70, are essential in the reactivation of toxic protein aggregates that occur during translation or periods of stress. In the pathogen Mycobacterium tuberculosis (Mtb), the protective effect of chaperones extends to survival in the presence of host stresses, such as protein‐damaging oxidants. However, we lack a full understanding of the interplay of Hsps and other stress response genes in mycobacteria. Here, we employ genome‐wide transposon mutagenesis to identify the genes that support clpB function in Mtb. In addition to validating the role of ClpB in Mtb's response to oxidants, we show that HtpG, a homolog of Hsp90, plays a distinct role from ClpB in the proteotoxic stress response. While loss of neither clpB nor htpG is lethal to the cell, loss of both through genetic depletion or small molecule inhibition impairs recovery after exposure to host‐like stresses, especially reactive nitrogen species. Moreover, defects in cells lacking clpB can be complemented by overexpression of other chaperones, demonstrating that Mtb's stress response network depends upon finely tuned chaperone expression levels. These results suggest that inhibition of multiple chaperones could work in concert with host immunity to disable Mtb. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1111/mmi.14615 |
| الاتاحة: | http://dx.doi.org/10.1111/mmi.14615 https://onlinelibrary.wiley.com/doi/pdf/10.1111/mmi.14615 https://onlinelibrary.wiley.com/doi/full-xml/10.1111/mmi.14615 https://onlinelibrary.wiley.com/doi/am-pdf/10.1111/mmi.14615 |
| Rights: | http://onlinelibrary.wiley.com/termsAndConditions#am ; http://onlinelibrary.wiley.com/termsAndConditions#vor |
| رقم الانضمام: | edsbas.2ADC44F4 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1111/mmi.14615 |
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