Mycobacterial mutagenesis and drug resistance are controlled by phosphorylation- and cardiolipin-mediated inhibition of the RecA coprotease Journal Article


Authors: Wipperman, M. F.; Heaton, B. E.; Nautiyal, A.; Adefisayo, O.; Evans, H.; Gupta, R.; van Ditmarsch, D.; Soni, R.; Hendrickson, R.; Johnson, J.; Krogan, N.; Glickman, M. S.
Article Title: Mycobacterial mutagenesis and drug resistance are controlled by phosphorylation- and cardiolipin-mediated inhibition of the RecA coprotease
Abstract: Infection with Mycobacterium tuberculosis continues to cause substantial human mortality, in part because of the emergence of antimicrobial resistance. Antimicrobial resistance in tuberculosis is solely the result of chromosomal mutations that modify drug activators or targets, yet the mechanisms controlling the mycobacterial DNA-damage response (DDR) remain incompletely defined. Here, we identify RecA serine 207 as a multifunctional signaling hub that controls the DDR in mycobacteria. RecA S207 is phosphorylated after DNA damage, which suppresses the emergence of antibiotic resistance by selectively inhibiting the LexA coprotease function of RecA without affecting its ATPase or strand exchange functions. Additionally, RecA associates with the cytoplasmic membrane during the mycobacterial DDR, where cardiolipin can specifically inhibit the LexA coprotease function of unmodified, but not S207 phosphorylated, RecA. These findings reveal that RecA S207 controls mutagenesis and antibiotic resistance in mycobacteria through phosphorylation and cardiolipin-mediated inhibition of RecA coprotease function. Copyright © 2018 Elsevier Inc. All rights reserved.
Keywords: dna repair; tuberculosis; sos response; antibiotic response
Journal Title: Molecular Cell
Volume: 72
Issue: 1
ISSN: 1097-2765
Publisher: Cell Press  
Date Published: 2018-10-04
Start Page: 152
End Page: 161.e7
Language: English
DOI: 10.1016/j.molcel.2018.07.037
PUBMED: 30174294
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 1 November 2018 -- Source: Scopus
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