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Additional role for the ccd operon of F-plasmid as a transmissible persistence factor

Tripathi, Arti and Dewan, Pooja C and Barua, Bipasha and Varadarajan, Raghavan (2012) Additional role for the ccd operon of F-plasmid as a transmissible persistence factor. In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 109 (31). pp. 12497-12502.

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Official URL: http://dx.doi.org/10.1073/pnas.1121217109


Toxin-antitoxin (TA) systems are found on both bacterial plasmids and chromosomes, but in most cases their functional role is unclear. Gene knockouts often yield limited insights into functions of individual TA systems because of their redundancy. The well-characterized F-plasmid-based CcdAB TA system is important for F-plasmid maintenance. We have isolated several point mutants of the toxin CcdB that fail to bind to its cellular target, DNA gyrase, but retain binding to the antitoxin, CcdA. Expression of such mutants is shown to result in release of the WT toxin from a functional preexisting TA complex as well as derepression of the TA operon. One such inactive, active-site mutant of CcdB was used to demonstrate the contribution of CcdB to antibiotic persistence. Transient activation of WT CcdB either by coexpression of the mutant or by antibiotic/heat stress was shown to enhance the generation of drug-tolerant persisters in a process dependent on Lon protease and RecA. An F-plasmid containing a ccd locus can, therefore, function as a transmissible persistence factor.

Item Type: Journal Article
Additional Information: Copy right for this article belongs to NATL ACAD SCIENCES, 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
Keywords: CcdA-CcdB;conditional regulation;protein-protein interaction
Department/Centre: Division of Biological Sciences > Molecular Biophysics Unit
Depositing User: Francis Jayakanth
Date Deposited: 15 Oct 2012 05:10
Last Modified: 15 Oct 2012 05:10
URI: http://eprints.iisc.ac.in/id/eprint/45101

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