The surface-exposed NadA adhesin produced by a subset of capsular serogroup B 
strains of Neisseria meningitidis is currently being considered as a vaccine 
candidate to prevent invasive disease caused by a hypervirulent lineage of 
meningococci. Levels of NadA are known to be controlled by both transcriptional 
regulatory factors and a component of human saliva, 4-hydroxyphenylacetic acid. 
Herein, we confirmed the capacity of a DNA-binding protein termed FarR to 
negatively control nadA expression. We also found that a known transcriptional 
regulator of farR in N. gonorrhoeae termed MtrR can have a negative regulatory 
impact on farR and nadA expression, especially when over-expressed. 
MtrR-mediated repression of nadA was found to be direct, and its binding to a 
target DNA sequence containing the nadA promoter influenced formation and/or 
stability of FarR::nadA complexes. The complexity of the multi-layered 
regulation of nadA uncovered during this investigation suggests that N. 
meningitidis modulates NadA adhesin protein levels for the purpose of 
interacting with host cells yet avoiding antibody directed against surface 
exposed epitopes.