Mechanisms for Differential Protein Production in Toxin–Antitoxin Systems

dc.contributor.authorDeter, Heather S.en
dc.contributor.authorJensen, Roderick V.en
dc.contributor.authorMather, William H.en
dc.contributor.authorButzin, Nicholas C.en
dc.contributor.departmentCenter for Soft Matter and Biological Physicsen
dc.contributor.departmentBiological Sciencesen
dc.contributor.departmentPhysicsen
dc.date.accessioned2017-09-20T18:33:56Zen
dc.date.available2017-09-20T18:33:56Zen
dc.date.issued2017-07-04en
dc.date.updated2017-09-20T18:33:56Zen
dc.description.abstractToxin–antitoxin (TA) systems are key regulators of bacterial persistence, a multidrug-tolerant state found in bacterial species that is a major contributing factor to the growing human health crisis of antibiotic resistance. Type II TA systems consist of two proteins, a toxin and an antitoxin; the toxin is neutralized when they form a complex. The ratio of antitoxin to toxin is significantly greater than 1.0 in the susceptible population (non-persister state), but this ratio is expected to become smaller during persistence. Analysis of multiple datasets (RNA-seq, ribosome profiling) and results from translation initiation rate calculators reveal multiple mechanisms that ensure a high antitoxin-to-toxin ratio in the non-persister state. The regulation mechanisms include both translational and transcriptional regulation. We classified <i>E. coli</i> type II TA systems into four distinct classes based on the mechanism of differential protein production between toxin and antitoxin. We find that the most common regulation mechanism is translational regulation. This classification scheme further refines our understanding of one of the fundamental mechanisms underlying bacterial persistence, especially regarding maintenance of the antitoxin-to-toxin ratio.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationDeter, H.S.; Jensen, R.V.; Mather, W.H.; Butzin, N.C. Mechanisms for Differential Protein Production in Toxin–Antitoxin Systems. Toxins 2017, 9, 211.en
dc.identifier.doihttps://doi.org/10.3390/toxins9070211en
dc.identifier.urihttp://hdl.handle.net/10919/79341en
dc.language.isoenen
dc.publisherMDPIen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjecttoxin–antitoxin systemsen
dc.subjectpersisteren
dc.subjectRNA-seqen
dc.subjectribosome profilingen
dc.subjectRibo-Seqen
dc.titleMechanisms for Differential Protein Production in Toxin–Antitoxin Systemsen
dc.title.serialToxinsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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