An isogenic hemoglobin receptor-deficient mutant of Haemophilus ducreyi is attenuated in the human model of experimental infection.
Haemophilus ducreyi expresses a conserved hemoglobin-binding outer-membrane protein (HgbA). To test the role of HgbA in pathogenesis, we infected 9 adults with isolate 35000 and its isogenic hgbA-inactivated mutant (FX504) on their upper arms in a double-blinded, escalating dose-response study. Papules developed at similar rates at sites inoculated with the mutant or parent. The pustule-formation rate was 55% (95% confidence interval [CI], 30. 8%-78.5%) at parent sites and 0 (95% CI, 0-10.5%) at mutant sites (P<.0001). The recovery rate of H. ducreyi from surface cultures was 16% (n=142) from parent sites and 0 (n=213) from mutant sites (P<. 0001). H. ducreyi was recovered at biopsy from 6 of 7 parent sites and from 0 of 3 mutant sites. The results indicate that hemoglobin may be a critical source of heme or iron for the establishment of H. ducreyi infection in humans.
Al-Tawfiq
J A
JA
Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Fortney
K R
KR
Katz
B P
BP
Hood
A F
AF
Elkins
C
C
Spinola
S M
SM
D000328:Adult; D001425:Bacterial Outer Membrane Proteins / Q000502:physiology*; D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000502:physiology*; D002602:Chancroid / Q000209:etiology*; D005260:Female; D006191:Haemophilus ducreyi / Q000472:pathogenicity*; D006454:Hemoglobins / Q000502:physiology; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype
D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D006454:Hemoglobins; C017206:hemoglobin-binding protein, bacteria