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Insights into the global effect on Staphylococcus aureus growth arrest by induction of the endoribonuclease MazF toxin

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Sierra Roberto, Prados Julien, Panasenko Olesya O, Andrey Diego O, Fleuchot Betty, Redder Peter, Kelley William L, Viollier Patrick H, Renzoni Adriana,
Project Identification of RNA signatures in Staphylococcus aureus to detect low-level glycopeptide resistance (hVISA and VISA): an integration of clinical and basic research
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Original article (peer-reviewed)

Journal Nucleic Acids Research
Volume (Issue) 48(15)
Page(s) 8545 - 8561
Title of proceedings Nucleic Acids Research
DOI 10.1093/nar/gkaa617

Open Access

URL http://doi.org/10.1093/nar/gkaa617
Type of Open Access Publisher (Gold Open Access)

Abstract

AbstractA crucial bacterial strategy to avoid killing by antibiotics is to enter a growth arrested state, yet the molecular mechanisms behind this process remain elusive. The conditional overexpression of mazF, the endoribonuclease toxin of the MazEF toxin–antitoxin system in Staphylococcus aureus, is one approach to induce bacterial growth arrest, but its targets remain largely unknown. We used overexpression of mazF and high-throughput sequence analysis following the exact mapping of non-phosphorylated transcriptome ends (nEMOTE) technique to reveal in vivo toxin cleavage sites on a global scale. We obtained a catalogue of MazF cleavage sites and unearthed an extended MazF cleavage specificity that goes beyond the previously reported one. We correlated transcript cleavage and abundance in a global transcriptomic profiling during mazF overexpression. We observed that MazF affects RNA molecules involved in ribosome biogenesis, cell wall synthesis, cell division and RNA turnover and thus deliver a plausible explanation for how mazF overexpression induces stasis. We hypothesize that autoregulation of MazF occurs by directly modulating the MazEF operon, such as the rsbUVW genes that regulate the sigma factor SigB, including an observed cleavage site on the MazF mRNA that would ultimately play a role in entry and exit from bacterial stasis.
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