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Infection and Immunity, March 2001, p. 1488-1491, Vol. 69, No. 3
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.3.1488-1491.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

DsrA-Deficient Mutant of Haemophilus ducreyi Is Impaired in Its Ability To Infect Human Volunteers

Cliffton T. H. Bong,1 Robert E. Throm,2 Kate R. Fortney,1 Barry P. Katz,1 Antoinette F. Hood,1,3 Christopher Elkins,4,5 and Stanley M. Spinola1,2,6,*

Departments of Medicine,1 Microbiology and Immunology,2 Pathology and Laboratory Medicine,6 and Dermatology,3 Indiana University, School of Medicine, Indianapolis, Indiana 46202, and Departments of Medicine4 and Microbiology and Immunology,5 School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599

Received 5 October 2000/Returned for modification 16 November 2000/Accepted 24 November 2000

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.

* Corresponding author. Mailing address: 435 Emerson Hall, 545 Barnhill Dr., Indiana University, Indianapolis, IN 46202-5124. Phone: (317) 274-1427. Fax: (317) 274-1587. E-mail: sspinola{at}iupui.edu.

Infection and Immunity, March 2001, p. 1488-1491, Vol. 69, No. 3
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.3.1488-1491.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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