Neisserial TonB-dependent outer-membrane proteins: detection, regulation and distribution of three putative candidates identified from the genome sequences

Computer searches were carried out of the gonococcal and meningococcal geno me databases for previously unknown members of the TonB-dependent family (T df) of outer-membrane receptor proteins. Seven putative noncontiguous genes were found and three of these (identified in gonococcal strain FA1090) wer e chosen for further study. consensus motif analysis of the peptide sequenc es was consistent with the three genes encoding TonB-dependent receptors. I n view of the five previously characterized TonB-dependent proteins of path ogenic neisseriae, the putative genes were labelled tdfF, tdfG and tdfH. Td fF had homology with the siderophore receptors FpvA of Pseudomonas aerugino sa and FhuE of Escherichia coli, whereas TdfG and TdfH had homology with th e haemophore receptor HasR of Serratia marcescens. The aim of this project was to characterize these proteins and determine their expression, regulati on, distribution and surface exposure. Strain surveys of iron-stressed comm ensal and pathogenic neisseriae revealed that TdfF is unlikely to be expres sed, TdfG is expressed by gonococci only and that TdfH is expressed by both meningococci and gonococci. Expression of TdfH was unaffected by iron avai lability. Susceptibility of TdfH to cleavage by proteases in live gonococci was consistent with surface exposure of this protein. TdfH may function as a TonB-dependent receptor for a non-iron nutrient source. Furthermore, Tdf H is worthy of future investigation as a potential meningococcal vaccine ca ndidate as it is a highly conserved, widely distributed and surface-exposed outer-membrane protein.