PMID:11179317

Citation	Bong, CT, Throm, RE, Fortney, KR, Katz, BP, Hood, AF, Elkins, C and Spinola, SM (2001) DsrA-deficient mutant of Haemophilus ducreyi is impaired in its ability to infect human volunteers. Infect. Immun. 69:1488-91
Abstract	Haemophilus ducreyi produces an outer membrane protein called DsrA, which is required for serum resistance. An isogenic dsrA mutant, FX517, was constructed previously in H. ducreyi 35000. Compared to its parent, FX517 cannot survive in normal human serum. When complemented in trans with a plasmid containing dsrA, FX517 is converted to a serum-resistant phenotype (C. Elkins, K. J. Morrow, Jr., and B. Olsen, Infect. Immun. 68:1608-1619, 2000). To test whether dsrA was transcribed in vivo, we successfully amplified transcripts in five biopsies obtained from four experimentally infected human subjects. To test whether DsrA was required for virulence, six volunteers were experimentally infected with 35000 and FX517 and observed for papule and pustule formation. Each subject was inoculated with two doses (70 to 80 CFU) of live 35000 and 1 dose of heat-killed bacteria on one arm and with three doses (ranging from 35 to 800 CFU) of live FX517 on the other arm. Papules developed at similar rates at sites inoculated with the mutant or parent. However, mutant papule surface areas were significantly smaller than parent papules. The pustule formation rate was 58% (95% confidence interval [CI] of 28 to 85%) at 12 parent sites, and 0% (95% CI of 0 to 15%) at 18 mutant sites (P = 0.0004). Although biosafety regulations precluded our testing the complemented mutant in humans, these results suggest that expression of DsrA facilitates the ability of H. ducreyi to progress to the pustular stage of disease.
Links	PubMed PMC98046 Online version:10.1128/IAI.69.3.1488-1491.2001
Keywords	Adult; Bacterial Outer Membrane Proteins/genetics; Biopsy; Chancroid/etiology; Chloramphenicol/pharmacology; Female; Haemophilus ducreyi/genetics; Haemophilus ducreyi/isolation & purification; Haemophilus ducreyi/pathogenicity; Humans; Male; Microbial Sensitivity Tests; Mutation
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HAEDC:Q9K2H6		GO:0009405: pathogenesis	ECO:0000315:		P		Tables 1 and 2 show the results of inoculation with wild-type and DsrA mutant H. ducreyi. Table 1 shows that the mutant is impaired in its ability to cause papules. Table 2 shows that the mutant (at an increased dose) forms smaller papules than the wild-type, on par with the heat-inactivated wild-type.	complete CACAO 5378
HAEDC:Q9K2H6	involved_in	GO:0009405: pathogenesis	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

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