Identification of a novel anti-sigmaE factor in Neisseria meningitidis.
BACKGROUND
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 sigma factors which, in complex with RNA polymerase holoenzyme, recognize specific promoter determinants. sigma(E), 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 sigma(E) regulon of meningococci.


RESULTS
We show that meningococcal sigma(E) is part of the polycistronic operon NMB2140-NMB2145 and autoregulated. In addition we demonstrate that sigma(E) controls expression of methionine sulfoxide reductase (MsrA/MsrB). Moreover, we provide evidence that the activity of sigma(E) 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-sigma factor (ZAS) motif, a hall mark of a specific class of Zn(2+)-binding ASD proteins acting as anti-sigma factors. We demonstrate that Cys residues in ZAS, as well as the Cys residue on position 4, are essential for anti-sigma(E) 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 sigma(E).


CONCLUSIONS
Together, our results demonstrate that meningococci express a functional transcriptionally autoregulated sigma(E) factor, the activity of which is controlled by a novel meningococcal anti-sigma factor belonging to the ZAS family.
Academic Medical Center, Center for Infection and Immunity Amsterdam (CINIMA), Department of Medical Microbiology, Amsterdam, the Netherlands.
Carla Th P
CT
Hopman
Dave
D
Speijer
Arie
A
van der Ende
Yvonne
Y
Pannekoek
D000595:Amino Acid Sequence; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic; D051150:Methionine Sulfoxide Reductases / Q000378:metabolism; D008969:Molecular Sequence Data; D005810:Multigene Family; D009345:Neisseria meningitidis / Q000378:metabolism*; D012808:Sigma Factor / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D012808:Sigma Factor; C063202:sporulation-specific sigma factors; D051150:Methionine Sulfoxide Reductases; C027219:methionine sulfoxide reductase