Abstract
BackgroundFine tuning expression of genes is a prerequisite for the strictly human pathogen Neisseria meningitidis to survive hostile growth conditions and establish disease. Many bacterial species respond to stress by using alternative σ factors which, in complex with RNA polymerase holoenzyme, recognize specific promoter determinants. σE, encoded by rpoE (NMB2144) in meningococci, is known to be essential in mounting responses to environmental challenges in many pathogens. Here we identified genes belonging to the σE regulon of meningococci.ResultsWe show that meningococcal σE is part of the polycistronic operon NMB2140-NMB2145 and autoregulated. In addition we demonstrate that σE controls expression of methionine sulfoxide reductase (MsrA/MsrB). Moreover, we provide evidence that the activity of σE is under control of NMB2145, directly downstream of rpoE. The protein encoded by NMB2145 is structurally related to anti-sigma domain (ASD) proteins and characterized by a zinc containing anti-σ factor (ZAS) motif, a hall mark of a specific class of Zn2+-binding ASD proteins acting as anti-σ factors. We demonstrate that Cys residues in ZAS, as well as the Cys residue on position 4, are essential for anti-σE activity of NMB2145, as found for a minority of members of the ZAS family that are predicted to act in the cytoplasm and responding to oxidative stimuli. However, exposure of cells to oxidative stimuli did not result in altered expression of σE.ConclusionsTogether, our results demonstrate that meningococci express a functional transcriptionally autoregulated σE factor, the activity of which is controlled by a novel meningococcal anti-σ factor belonging to the ZAS family.
Highlights
Fine tuning expression of genes is a prerequisite for the strictly human pathogen Neisseria meningitidis to survive hostile growth conditions and establish disease
The gene cluster containing rpoE is transcribed as a polycistronic operon and transcriptionally regulated by σE In many bacterial species, rpoE is part of an autoregulated polycistronic operon encoding its cognate antisigma factor [25,26,27,28]
We provide strong evidence that NMB2145, encodes a novel anti-σ factor structurally related to anti-sigma domain (ASD) proteins and containing the ZAS motif, making NMB2145 the first anti-σ-factor described for any neisserial species
Summary
Fine tuning expression of genes is a prerequisite for the strictly human pathogen Neisseria meningitidis to survive hostile growth conditions and establish disease. Many bacterial species respond to stress by using alternative σ factors which, in complex with RNA polymerase holoenzyme, recognize specific promoter determinants. The σ factor contains many of the promoter recognition determinants and several σ factors each recognizing their specific class of promoter sequences have been described [1,2,3,4,5]. Alternative σ factors mediate transcription of regulons activated under specific environmental conditions [7,8]. 95% (227/ 248) are characterized by the presence of an invariant Hisx3Cysx2Cys sequence motif important for anti-sigma activity, co-ordinating Zn2+, described as the zinc containing anti-σ factor (ZAS) group IV anti-σs proteins [29]. ASD proteins and ASD proteins containing the ZAS motif are predicted to bind to σs and inhibit their activities [25,26,27,28]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
