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Role of toxin ζ and starvation responses in the sensitivity to antimicrobials

AuthorsTabone, Mariangela; Lioy, Virginia S.; Ayora, Silvia ; Machón, Cristina ; Alonso, Juan Carlos
KeywordsCellular stress responses
Bacillus subtilis
Cell physiology
Confidence intervals
Gene pool
Issue Date29-Jan-2014
PublisherPublic Library of Science
CitationPLoS ONE 9(1): e86615 (2014)
AbstractA fraction of otherwise antimicrobial-sensitive Bacillus subtilis cells, called persisters, are phenotypically tolerant of antimicrobial treatment. We report that, independently of B. subtilis' growth phase, transient ζ toxin expression induces a dormant state and alters cellular responses so that cells are more sensitive to antimicrobials with different modes of action. This outcome is modulated by fine tuning (p)ppGpp and GTP levels: i) in the presence of low >dysregulated> (p)ppGpp levels (as in relA- cells) hyper-tolerance to both toxin and antimicrobials was observed; ii) physiological or low (p)ppGpp levels (as in the wild-type, sasA-, sasB- and relA- sasA- context) show a normal toxin and antimicrobial tolerance; and iii) lower levels (in relA- sasB -) or absence of (p)ppGpp (in the relA- sasA- sasB- context), in concert with elevated GTP levels, potentiate the efficacy of both toxin and antimicrobial action, rendering tolerance vulnerable to eradication. © 2014 Tabone et al.
Publisher version (URL)http://dx.doi.org/10.1371/journal.pone.0086615
Identifiersdoi: 10.1371/journal.pone.0086615
issn: 1932-6203
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