Molecular Characterization of<i>Haemophilus ducreyi</i>Strains from Jackson, Mississippi, and New Orleans, Louisiana

Haydock, Andrew; Martín, David H.; Morse, Stephen; Cammarata, Cathy; Mertz, Kristen J.; Totten, Patricia A.

doi:10.1086/314771

Cited by 18 publications

(12 citation statements)

References 30 publications

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“…Molecular analyses showed some differences, e.g., ribotyping of strains from two outbreaks yielded multiple restriction fragment length polymorphism (RFLP) patterns (19), but designations based on these differences have not been widely adopted or used for epidemiologic studies, in part due to the difficulty in culturing this fastidious organism. The lack of a standard typing system makes epidemiologic studies more difficult, and epidemiologic data for chancroid are therefore limited.…”

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Rapid Divergence of Two Classes of Haemophilus ducreyi

et al. 2011

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Haemophilus ducreyi, the etiologic agent of chancroid, expresses variants of several key virulence factors. While previous reports suggested that H. ducreyi strains formed two clonal populations, the differences between, and diversity within, these populations were unclear. To assess their variability, we examined sequence diversity at 11 H. ducreyi loci, including virulence and housekeeping genes, augmenting published data sets with PCR-amplified genes to acquire data for at least 10 strains at each locus. While sequences from all 11 loci place strains into two distinct groups, there was very little variation within each group. The difference between alleles of the two groups was variable and large at 3 loci encoding surface-exposed proteins (0.4 < K S < 1.3, where K S is divergence at synonymous sites) but consistently small at genes encoding cytoplasmic or periplasmic proteins (K S < 0.09). The data suggest that the two classes have recently diverged, that recombination has introduced variant alleles into at least 3 distinct loci, and that these alleles have been confined to one of the two classes. In addition, recombination is evident among alleles within, but not between, classes. Rather than clones of the same species, these properties indicate that the two classes may form distinct species.Haemophilus ducreyi is a Gram-negative coccobacillus in the family Pasteurellaceae (2) and the causative agent of chancroid, a sexually transmitted, genital ulcer disease which facilitates transmission of 14,23,44). While H. ducreyi was placed in the polyphyletic genus Haemophilus due to its requirement for hemin, Haemophilus species do not form a cohesive group within the Pasteurellaceae (6, 20). The species that are most closely related to H. ducreyi include Actinobacter pleuropneumoniae and Nicoletella semolina (see Fig. S1 in the supplemental material) (16).Previous attempts to examine the diversity within the species H. ducreyi using immunotyping (36) and outer membrane profiling (32) showed very few differences among strains. Molecular analyses showed some differences, e.g., ribotyping of strains from two outbreaks yielded multiple restriction fragment length polymorphism (RFLP) patterns (19), but designations based on these differences have not been widely adopted or used for epidemiologic studies, in part due to the difficulty in culturing this fastidious organism. The lack of a standard typing system makes epidemiologic studies more difficult, and epidemiologic data for chancroid are therefore limited.One way to study diversity in H. ducreyi is to assess its population structure. Whereas the lack of recombination in some bacterial species generates stable clones (5), others recombine sufficiently rapidly to obscure clonal relationships (10, 11). While many Haemophilus species are naturally competent, H. ducreyi is considered nontransformable due to defects in the DNA uptake apparatus (16,34). This would likely decrease rates of recombination and generate stable clones. Initial studies of the clonal structure of...

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Rapid Divergence of Two Classes of Haemophilus ducreyi

et al. 2011

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“…In some resource-poor developing countries of Asia, Africa, and Latin America, chancroid is a very common sexually transmitted infection (reviewed in reference 54). In the United States, chancroid is very rarely seen but outbreaks in urban areas have been documented (23,40) and this disease may be underreported (52). The public health consequences of chancroid are not insignificant, because the presence of genital ulcers caused by H. ducreyi increases the likelihood of heterosexual transmission of HIV-1 infection (20,51).…”

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Characterization of the CpxRA Regulon in Haemophilus ducreyi

Labandeira-Rey¹,

Brautigam

Hansen³

2010

Infect Immun

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The Haemophilus ducreyi 35000HP genome encodes a homolog of the CpxRA two-component cell envelope stress response system originally characterized in Escherichia coli. CpxR, the cytoplasmic response regulator, was shown previously to be involved in repression of the expression of the lspB-lspA2 operon (M. LabandeiraRey, J. R. Mock, and E. J. Hansen, Infect. Immun. 77:3402-3411, 2009). In the present study, the H. ducreyi CpxR and CpxA proteins were shown to closely resemble those of other well-studied bacterial species. A cpxA deletion mutant and a CpxR-overexpressing strain were used to explore the extent of the CpxRA regulon. DNA microarray and real-time reverse transcriptase (RT) PCR analyses indicated several potential regulatory targets for the H. ducreyi CpxRA two-component regulatory system. Electrophoretic mobility shift assays (EMSAs) were used to prove that H. ducreyi CpxR interacted with the promoter regions of genes encoding both known and putative virulence factors of H. ducreyi, including the lspB-lspA2 operon, the flp operon, and dsrA. Interestingly, the use of EMSAs also indicated that H. ducreyi CpxR did not bind to the promoter regions of several genes predicted to encode factors involved in the cell envelope stress response. Taken together, these data suggest that the CpxRA system in H. ducreyi, in contrast to that in E. coli, may be involved primarily in controlling expression of genes not involved in the cell envelope stress response.

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“…Frequencies of both acquisition and transmission of human immunodeficiency virus type 1 infection are increased by the presence of chancroidal ulcers (12,15). While chancroid is extremely uncommon in the United States, outbreaks have occurred in urban areas (19).…”

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Haemophilus ducreyi Targets Src Family Protein Tyrosine Kinases To Inhibit Phagocytic Signaling

et al. 2005

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Haemophilus ducreyi, the etiologic agent of the sexually transmitted disease chancroid, has been shown to inhibit phagocytosis of both itself and secondary targets in vitro. Immunodepletion of LspA proteins from H. ducreyi culture supernatant fluid abolished this inhibitory effect, indicating that the LspA proteins are necessary for the inhibition of phagocytosis by H. ducreyi. Fluorescence microscopy revealed that macrophages incubated with wild-type H. ducreyi, but not with a lspA1 lspA2 mutant, were unable to complete development of the phagocytic cup around immunoglobulin G-opsonized targets. Examination of the phosphotyrosine protein profiles of these two sets of macrophages showed that those incubated with wild-type H. ducreyi had greatly reduced phosphorylation levels of proteins in the 50-to-60-kDa range. Subsequent experiments revealed reductions in the catalytic activities of both Lyn and Hck, two members of the Src family of protein tyrosine kinases that are known to be involved in the proximal signaling steps of Fc␥ receptor-mediated phagocytosis. Additional experiments confirmed reductions in the levels of both active Lyn and active Hck in three different immune cell lines, but not in HeLa cells, exposed to wild-type H. ducreyi. This is the first example of a bacterial pathogen that suppresses Src family protein tyrosine kinase activity to subvert phagocytic signaling in host cells.

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Molecular Characterization ofHaemophilus ducreyiStrains from Jackson, Mississippi, and New Orleans, Louisiana

Cited by 18 publications

References 30 publications

Rapid Divergence of Two Classes of Haemophilus ducreyi

Rapid Divergence of Two Classes of Haemophilus ducreyi

Characterization of the CpxRA Regulon in Haemophilus ducreyi

Haemophilus ducreyi Targets Src Family Protein Tyrosine Kinases To Inhibit Phagocytic Signaling

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