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Toxin GhoT of the GhoT / GhoS toxin/antitoxin system damages the cell membrane to reduce adenosine triphosphate and to reduce growth under stress
Author(s) -
Cheng HsinYao,
Soo Valerie W. C.,
Islam Sabina,
McAnulty Michael J.,
Benedik Michael J.,
Wood Thomas K.
Publication year - 2014
Publication title -
environmental microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.954
H-Index - 188
eISSN - 1462-2920
pISSN - 1462-2912
DOI - 10.1111/1462-2920.12373
Subject(s) - endoribonuclease , antitoxin , biology , toxin , intracellular , microbiology and biotechnology , cell membrane , adenosine triphosphate , lysis , cell , biochemistry , biophysics , rna , rnase p , gene
Summary Toxin/antitoxin ( TA ) systems perhaps enable cells to reduce their metabolism to weather environmental challenges although there is little evidence to support this hypothesis. E scherichia coli GhoT / GhoS is a TA system in which toxin GhoT expression is reduced by cleavage of its messenger RNA ( mRNA ) by antitoxin GhoS , and TA system MqsR / MqsA controls GhoT / GhoS through differential mRNA decay. However, the physiological role of GhoT has not been determined. We show here through transmission electron microscopy, confocal microscopy and fluorescent stains that GhoT reduces metabolism by damaging the membrane and that toxin MqsR (a 5′‐ GCU ‐specific endoribonuclease) causes membrane damage in a GhoT ‐dependent manner. This membrane damage results in reduced cellular levels of ATP and the disruption of proton motive force ( PMF ). Normally, GhoT is localized to the pole and does not cause cell lysis under physiological conditions. Introduction of an F38R substitution results in loss of GhoT toxicity, ghost cell production and membrane damage while retaining the pole localization. Also, deletion of ghoST or ghoT results in significantly greater initial growth in the presence of antimicrobials. Collectively, these results demonstrate that GhoT reduces metabolism by reducing ATP and PMF and that this reduction in metabolism is important for growth with various antimicrobials.