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Updated: Aug 30, 2026

TransFLP — A Method to Genetically Modify Vibrio cholerae Based on Natural Transformation and FLP-recombination
Published on: October 8, 2012
Haemophilus ducreyi requires an intact flp gene cluster for virulence in humans
Stanley M Spinola1, Kate R Fortney, Barry P Katz
1Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. sspinola@iupui.edu
Abstract:
An intact Haemophilus ducreyi flp operon is essential for microcolony formation in vitro. tadA is the 9th of 15 genes in the operon and has homology to NTPases of type IV secretion systems. Fifteen human volunteers were experimentally infected with both H. ducreyi 35000HP and the tadA mutant, 35000HP.400. Papules developed at similar rates at sites inoculated with the mutant and parent, while pustules formed at 36.4% of parent sites and at 0% of mutant sites (P = 0.001). Compared to 35000HP, 35000HP.400 had only a modest but significant reduction in lesion scores in the temperature-dependent rabbit model of chancroid. These data suggest that proteins secreted by the flp locus are required for full expression of virulence by H. ducreyi in humans but have less of a role in virulence in an animal model of infection.
Insights
The Haemophilus ducreyi flp operon is vital for microcolony formation. A tadA mutant showed reduced pustule formation in humans, indicating flp locus proteins are key for H. ducreyi virulence in people.
Area of Science:
- Microbiology
- Bacterial Pathogenesis
- Infectious Diseases
Background:
- Haemophilus ducreyi causes chancroid, a sexually transmitted infection.
- The flp operon and its gene tadA are implicated in bacterial virulence and secretion systems.
Purpose of the Study:
- To investigate the role of the tadA gene within the H. ducreyi flp operon in virulence.
- To compare the virulence of a tadA mutant and wild-type H. ducreyi in human and animal models.
Main Methods:
- Experimental infection of human volunteers with wild-type H. ducreyi and a tadA mutant.
- Assessment of lesion development (papules and pustules) in human participants.
- Evaluation of lesion scores in a temperature-dependent rabbit model of chancroid.
Main Results:
- Papule formation rates were similar between the mutant and wild-type strains in humans.
- Pustule formation was significantly reduced in human sites inoculated with the tadA mutant (0%) compared to the wild-type (36.4%).
- The tadA mutant showed a modest but significant reduction in lesion scores in the rabbit model.
Conclusions:
- Proteins secreted by the flp locus are essential for full H. ducreyi virulence in humans, particularly for pustule development.
- The flp locus plays a less significant role in virulence in the rabbit model of chancroid compared to human infections.
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