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Haemophilus ducreyi Cutaneous Ulcer Strains Are Nearly Identical to Class I Genital Ulcer Strains.

Gangaiah D, Webb KM, Humphreys TL, Fortney KR, Toh E, Tai A, Katz SS, Pillay A, Chen CY, Roberts SA, Munson RS, Spinola SM - PLoS Negl Trop Dis (2015)

Bottom Line: In human volunteers, the GU strain 35000HP does not infect intact skin; wounds are required to initiate infection.These data suggest that CU strains are derivatives of class I strains that were not recognized until recently.These findings require confirmation by analysis of CU strains from other regions.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.

ABSTRACT

Background: Although cutaneous ulcers (CU) in the tropics is frequently attributed to Treponema pallidum subspecies pertenue, the causative agent of yaws, Haemophilus ducreyi has emerged as a major cause of CU in yaws-endemic regions of the South Pacific islands and Africa. H. ducreyi is generally susceptible to macrolides, but CU strains persist after mass drug administration of azithromycin for yaws or trachoma. H. ducreyi also causes genital ulcers (GU) and was thought to be exclusively transmitted by microabrasions that occur during sex. In human volunteers, the GU strain 35000HP does not infect intact skin; wounds are required to initiate infection. These data led to several questions: Are CU strains a new variant of H. ducreyi or did they evolve from GU strains? Do CU strains contain additional genes that could allow them to infect intact skin? Are CU strains susceptible to azithromycin?

Methodology/principal findings: To address these questions, we performed whole-genome sequencing and antibiotic susceptibility testing of 5 CU strains obtained from Samoa and Vanuatu and 9 archived class I and class II GU strains. Except for single nucleotide polymorphisms, the CU strains were genetically almost identical to the class I strain 35000HP and had no additional genetic content. Phylogenetic analysis showed that class I and class II strains formed two separate clusters and CU strains evolved from class I strains. Class I strains diverged from class II strains ~1.95 million years ago (mya) and CU strains diverged from the class I strain 35000HP ~0.18 mya. CU and GU strains evolved under similar selection pressures. Like 35000HP, the CU strains were highly susceptible to antibiotics, including azithromycin.

Conclusions/significance: These data suggest that CU strains are derivatives of class I strains that were not recognized until recently. These findings require confirmation by analysis of CU strains from other regions.

No MeSH data available.


Related in: MedlinePlus

Whole-genome heat map showing the pairwise genome conservation distances of the CU and GU strains.The genome conservation distances were calculated using ProgressiveMauve; the distance matrix was plotted as an heat map using CIMminer with heat map clustering methods. Dendrograms across the top and left of the heat map show the relationship of genomes based on genome conservation. The strain names are indicated to the right and bottom of the heat map. Distance values range from 0.0000 to 0.1207, which are depicted by the gradient of colors ranging from dark blue (lowest distance value indicating high similarity between genomes) to red (highest distance value indicating low similarity between genomes).
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pntd.0003918.g001: Whole-genome heat map showing the pairwise genome conservation distances of the CU and GU strains.The genome conservation distances were calculated using ProgressiveMauve; the distance matrix was plotted as an heat map using CIMminer with heat map clustering methods. Dendrograms across the top and left of the heat map show the relationship of genomes based on genome conservation. The strain names are indicated to the right and bottom of the heat map. Distance values range from 0.0000 to 0.1207, which are depicted by the gradient of colors ranging from dark blue (lowest distance value indicating high similarity between genomes) to red (highest distance value indicating low similarity between genomes).

Mentions: Analysis of pairwise genome conservation distance of the draft genomes showed that CU strains form a subcluster within class I strains and that class II strains form a separate cluster from CU and class I strains (Fig 1).


Haemophilus ducreyi Cutaneous Ulcer Strains Are Nearly Identical to Class I Genital Ulcer Strains.

Gangaiah D, Webb KM, Humphreys TL, Fortney KR, Toh E, Tai A, Katz SS, Pillay A, Chen CY, Roberts SA, Munson RS, Spinola SM - PLoS Negl Trop Dis (2015)

Whole-genome heat map showing the pairwise genome conservation distances of the CU and GU strains.The genome conservation distances were calculated using ProgressiveMauve; the distance matrix was plotted as an heat map using CIMminer with heat map clustering methods. Dendrograms across the top and left of the heat map show the relationship of genomes based on genome conservation. The strain names are indicated to the right and bottom of the heat map. Distance values range from 0.0000 to 0.1207, which are depicted by the gradient of colors ranging from dark blue (lowest distance value indicating high similarity between genomes) to red (highest distance value indicating low similarity between genomes).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492979&req=5

pntd.0003918.g001: Whole-genome heat map showing the pairwise genome conservation distances of the CU and GU strains.The genome conservation distances were calculated using ProgressiveMauve; the distance matrix was plotted as an heat map using CIMminer with heat map clustering methods. Dendrograms across the top and left of the heat map show the relationship of genomes based on genome conservation. The strain names are indicated to the right and bottom of the heat map. Distance values range from 0.0000 to 0.1207, which are depicted by the gradient of colors ranging from dark blue (lowest distance value indicating high similarity between genomes) to red (highest distance value indicating low similarity between genomes).
Mentions: Analysis of pairwise genome conservation distance of the draft genomes showed that CU strains form a subcluster within class I strains and that class II strains form a separate cluster from CU and class I strains (Fig 1).

Bottom Line: In human volunteers, the GU strain 35000HP does not infect intact skin; wounds are required to initiate infection.These data suggest that CU strains are derivatives of class I strains that were not recognized until recently.These findings require confirmation by analysis of CU strains from other regions.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.

ABSTRACT

Background: Although cutaneous ulcers (CU) in the tropics is frequently attributed to Treponema pallidum subspecies pertenue, the causative agent of yaws, Haemophilus ducreyi has emerged as a major cause of CU in yaws-endemic regions of the South Pacific islands and Africa. H. ducreyi is generally susceptible to macrolides, but CU strains persist after mass drug administration of azithromycin for yaws or trachoma. H. ducreyi also causes genital ulcers (GU) and was thought to be exclusively transmitted by microabrasions that occur during sex. In human volunteers, the GU strain 35000HP does not infect intact skin; wounds are required to initiate infection. These data led to several questions: Are CU strains a new variant of H. ducreyi or did they evolve from GU strains? Do CU strains contain additional genes that could allow them to infect intact skin? Are CU strains susceptible to azithromycin?

Methodology/principal findings: To address these questions, we performed whole-genome sequencing and antibiotic susceptibility testing of 5 CU strains obtained from Samoa and Vanuatu and 9 archived class I and class II GU strains. Except for single nucleotide polymorphisms, the CU strains were genetically almost identical to the class I strain 35000HP and had no additional genetic content. Phylogenetic analysis showed that class I and class II strains formed two separate clusters and CU strains evolved from class I strains. Class I strains diverged from class II strains ~1.95 million years ago (mya) and CU strains diverged from the class I strain 35000HP ~0.18 mya. CU and GU strains evolved under similar selection pressures. Like 35000HP, the CU strains were highly susceptible to antibiotics, including azithromycin.

Conclusions/significance: These data suggest that CU strains are derivatives of class I strains that were not recognized until recently. These findings require confirmation by analysis of CU strains from other regions.

No MeSH data available.


Related in: MedlinePlus