The ntrPR Operon of Sinorhizobium meliloti Is Organized and Functions as a Toxin-Antitoxin Module

Abstract

The chromosomal ntrPR operon of Sinorhizobium meliloti encodes a protein pair that forms a toxin-antitoxin (TA) module, the first characterized functional TA system in Rhizobiaceae. Similarly to other bacterial TA systems, the toxin gene ntrR is preceded by and partially overlaps with the antitoxin gene ntrP. Based on protein homologies, the ntrPR operon belongs to the vapBC family of TA systems. The operon is negatively autoregulated by the NtrPNtrR complex. Promoter binding by NtrP is weak; stable complex formation also requires the presence of NtrR. The N-terminal part of NtrP is responsible for the interaction with promoter DNA, whereas the C-terminal part is required for protein-protein interactions. In the promoter region, a direct repeat sequence was identified as the binding site of the NtrPNtrR complex. NtrR expression resulted in the inhibition of cell growth and colony formation; this effect was counteracted by the presence of the antitoxin NtrP. These results and our earlier observations demonstrating a less effective downregulation of a wide range of symbiotic and metabolic functions in the ntrR mutant under microoxic conditions and an increased symbiotic efficiency with the host plant alfalfa suggest that the ntrPR module contributes to adjusting metabolic levels under symbiosis and other stressful conditions.

Molecular Characterization of Protease Activity in Serratia sp. Strain SCBI and Its Importance in Cytotoxicity and Virulence

“…The largest class of type II toxin-antitoxin systems in prokaryotes is the VapBC TA system, in which VapC is the toxin and VapB serves as the matching antitoxin. VapBC TAs in such organisms as Sinorhizobium meliloti, Mycobacterium smegmatis, and Neisseria gonorrhoeae appear be involved in metabolic processes during host interactions and under stressful conditions by targeting an array of mRNA transcripts for degradation (58)(59)(60). The VapBC TAs in Salmonella enterica and Shigella flexneri are induced by amino acid starvation and chloramphenicol, resulting in a bacteriostatic condition (61).…”

Protein expression, crystallization and preliminary X-ray crystallographic analysis of the isolatedShigella flexneriVapC toxin

“…Crystal structures have been determined of both VapBC-like complexes and isolated VapC-like toxins from archaea and pathogenic bacteria, which show a great diversity in both sequence and structure, as well as the cellular target of the toxin (Bunker et al, 2008;Mattison et al, 2006;Miallau et al, 2009). As in most other TA systems, VapBC complexes bind to the operator sequences of their own promoter region and down-regulate transcription from the operon (Bodogai et al, 2006;Wilbur et al, 2005). A recent crystal structure of the intact VapBC complex from the Gram-negative pathogen Shigella flexneri revealed the DNA-binding complex is a compact hetero-octameric assembly with the two DNA-binding domains juxtaposed in a manner compatible with adjacent majorgroove binding (Dienemann et al, 2011).…”

The vapBC Operon from Mycobacterium smegmatis Is An Autoregulated Toxin–Antitoxin Module That Controls Growth via Inhibition of Translation

“…Similar to fitAB from N. gonorrhoeae, the function of ntrPR is to regulate metabolic rates in specific environments. 15 In Leptospira interrogans, the biological role of vapBC is not well defined, but expression of L.…”