Evaluation of the repertoire of the TonB-dependent receptors of Haemophilus ducreyi for their role in virulence in humans.
Haemophilus ducreyi contains 3 TonB-dependent receptors: the hemoglobin receptor HgbA, which is required for virulence in humans; the heme receptor TdhA; and an uncharacterized conserved hypothetical protein TdX (HD0646). A double tdX/tdhA mutant (FX527) was constructed on the background of a human-passaged variant of strain 35000 (35000HP). Six volunteers were infected with 35000HP at 3 sites on one arm and with FX527 at 3 sites on the other. The pustule formation rate was 55.6% (95% confidence interval [CI], 35.7%-75.4%) at 18 parent-strain sites and 44.4% (95% CI, 15.0%-73.9%) at 18 mutant-strain sites (P = .51). Similar amounts of 35000HP and FX527 were recovered from pustules in semiquantitative culture. Thus, TdX and TdhA are not necessary for virulence, whereas HgbA is both necessary and sufficient for virulence in humans. The data suggest that hemoglobin is the sole source of heme/iron used by H. ducreyi in vivo and has implications for the potential of HgbA as a vaccine.
Leduc
Isabelle
I
Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill 27599, USA.
Banks
Keith E
KE
Fortney
Kate R
KR
Patterson
Kristine B
KB
Billings
Steve D
SD
Katz
Barry P
BP
Spinola
Stanley M
SM
Elkins
Christopher
C
D000328:Adult; D001425:Bacterial Outer Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000235:genetics; D001706:Biopsy; D015153:Blotting, Western; D002602:Chancroid / Q000382:microbiology*; D004269:DNA, Bacterial / Q000235:genetics / Q000378:metabolism; D005260:Female; D006191:Haemophilus ducreyi / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D016254:Mutagenesis, Insertional; D016133:Polymerase Chain Reaction; D014774:Virulence
D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D008565:Membrane Proteins; C057616:tonB protein, Bacteria