Expression of the meningococcal adhesin NadA is controlled by a transcriptional regulator of the MarR family.
Two closely related pathogenic species have evolved in the genus Neisseria: N. meningitidis and N. gonorrhoeae, which occupy different host niches and cause different clinical entities. In contrast to the pathogen N. gonorrhoeae, N. meningitidis is a commensal and only rarely becomes invasive. Little is known about the genetic background of the entirely different lifestyles in these closely related species. Meningococcal NMB1843 encodes a transcriptional regulator of the MarR family. The gonococcal homologue FarR regulates expression of farAB, mediating fatty acid resistance. We show that NmFarR also directly interacts with NmfarAB. Yet, by contrast to N. gonorrhoeae, no significant sensitivity to fatty acids was observed in a DeltafarR mutant due to intrinsic resistance of meningococci. Further analyses identified an NmFarR-repressed protein absent from N. gonorrhoeae. This protein is the meningococcus-specific adhesin and vaccine component NadA that has most likely been acquired by horizontal gene transfer. NmFarR binds to a 16 base pair palindromic repeat within the nadA promoter. De-repression of nadA resulted in significantly higher association of a DeltafarR strain with epithelial cells. Hence NmFarR has gained control over a meningococcus-specific gene involved in host colonization and thus contributed to divergent niche adaptation in pathogenic Neisseriae.
Schielke
Stephanie
S
University of Würzburg, Institute of Hygiene and Microbiology, Würzburg, Germany.
Huebner
Claudia
C
Spatz
Carolin
C
Nägele
Virginie
V
Ackermann
Nikolaus
N
Frosch
Matthias
M
Kurzai
Oliver
O
Schubert-Unkmeir
Alexandra
A
D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D001665:Binding Sites; D002460:Cell Line; D003001:Cloning, Molecular; D004269:DNA, Bacterial / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D006801:Humans; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D009345:Neisseria meningitidis / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D018829:Adhesins, Bacterial; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; C501982:NadA protein, Neisseria meningitidis; D014157:Transcription Factors