PMID:18398006

Citation	Liu, M, Zhang, Y, Inouye, M and Woychik, NA (2008) Bacterial addiction module toxin Doc inhibits translation elongation through its association with the 30S ribosomal subunit. Proc. Natl. Acad. Sci. U.S.A. 105:5885-90
Abstract	Bacterial toxin-antitoxin (TA) systems (or "addiction modules") typically facilitate cell survival during intervals of stress by inducing a state of reversible growth arrest. However, upon prolonged stress, TA toxin action leads to cell death. TA systems have also been implicated in several clinically important phenomena: biofilm formation, bacterial persistence during antibiotic treatment, and bacterial pathogenesis. TA systems harbored by pathogens also serve as attractive antibiotic targets. To date, the mechanism of action of the majority of known TA toxins has not yet been elucidated. We determined the mode of action of the Doc toxin of the Phd-Doc TA system. Doc expression resulted in rapid cell growth arrest and marked inhibition of translation without significant perturbation of transcription or replication. However, Doc did not cleave mRNA as do other addiction-module toxins whose activities result in translation inhibition. Instead, Doc induction mimicked the effects of treatment with the aminoglycoside antibiotic hygromycin B (HygB): Both Doc and HygB interacted with 30S ribosomal subunits, stabilized polysomes, and resulted in a significant increase in mRNA half-life. HygB also competed with ribosome-bound Doc, whereas HygB-resistant mutants suppressed Doc toxicity, suggesting that the Doc-binding site includes that of HygB (i.e., helix 44 region of 16S rRNA containing the A, P, and E sites). Overall, our results illuminate an intracellular target and mechanism of TA toxin action drawn from aminoglycoside antibiotics: Doc toxicity is the result of inhibition of translation elongation, possibly at the translocation step, through its interaction with the 30S ribosomal subunit.
Links	PubMed PMC2311363 Online version:10.1073/pnas.0711949105
Keywords	Bacteriophage P1/chemistry; Binding Sites; Protein Binding; Protein Biosynthesis/drug effects; RNA Stability/drug effects; Ribosomes/metabolism; Viral Proteins/pharmacology
edit table

Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
BPP1:PHD		GO:0044696: killing by virus of host cell by post-segregational killing	ECO:0000314:		P		Figure 2. Shows Phd can recover the wild type phenotype that was lost by Doc. NOTE: GO-Terms requested. NTR: Regulation of killing by virus of host cell by post-segregational killing NTR: Negative regulation of killing by virus of host cell by post-segregational killing NTR: Negative regulation by virus of killing by virus of host cell by post-segregational killing	complete CACAO 10394
BPP1:DOC		GO:0039604: suppression by virus of host translation	ECO:0000314:		P		Figure 1. Shows total protein levels decreases over time when Doc (from P1 phage) is present.	complete CACAO 10364
BPP1:DOC	involved_in	GO:0039604: suppression by virus of host translation	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

References

See Help:References for how to manage references in GONUTS.