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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

Circular visualization of multiple alignment of the CU and GU strains using Blast Ring Image Generator.The draft genomes of the CU and GU strains were mapped to 35000HP using nucleotide BLAST. The innermost ring showing the genomic positions represents the reference genome 35000HP. For clarity, each ring representing each strain is indicated by a different color. Positions covered by nucleotide BLAST are indicated as solid color, while positions not covered by nucleotide BLAST are indicated as white spaces. The gene coordinates of potential large-scale deletions are indicated.
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pntd.0003918.g002: Circular visualization of multiple alignment of the CU and GU strains using Blast Ring Image Generator.The draft genomes of the CU and GU strains were mapped to 35000HP using nucleotide BLAST. The innermost ring showing the genomic positions represents the reference genome 35000HP. For clarity, each ring representing each strain is indicated by a different color. Positions covered by nucleotide BLAST are indicated as solid color, while positions not covered by nucleotide BLAST are indicated as white spaces. The gene coordinates of potential large-scale deletions are indicated.

Mentions: Compared to 35000HP, all the CU strains consistently contained ~20-kb deletion (HD1528 to HD1565) in a bacteriophage locus that is homologous to Pseudomonas aeruginosa bacteriophage B3 and five small deletions that ranged in size from 30–767 bp (Fig 2 and S2 Table). The class I strain HMC56 contained a 50-kb deletion (HD0897 to tRNA-Lys-1) in a region homologous to the H. influenzae ICEHin1056 integrative conjugative element (Fig 2 and S3 Table). All the class II strains contained 3 major deletions of 37 kb (HD0087 to HD0161), 35 kb (HD0478 to HD0495) and 50 kb (HD0897 to tRNA-Lys-1), which are homologous to Escherichia coli bacteriophage D108, Haemophilus bacteriophage SuMu, and H. influenzae ICEHin1056, respectively (Fig 2 and S4 Table). The class II strains also contained several deletions (between HD1528 and HD1618) in a region that is homologous to P. aeruginosa bacteriophage B3 (Fig 2 and S4 Table). All the GU strains also contained several other small deletions as listed in S3 and S4 Tables.


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)

Circular visualization of multiple alignment of the CU and GU strains using Blast Ring Image Generator.The draft genomes of the CU and GU strains were mapped to 35000HP using nucleotide BLAST. The innermost ring showing the genomic positions represents the reference genome 35000HP. For clarity, each ring representing each strain is indicated by a different color. Positions covered by nucleotide BLAST are indicated as solid color, while positions not covered by nucleotide BLAST are indicated as white spaces. The gene coordinates of potential large-scale deletions are indicated.
© Copyright Policy
Related In: Results  -  Collection

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

pntd.0003918.g002: Circular visualization of multiple alignment of the CU and GU strains using Blast Ring Image Generator.The draft genomes of the CU and GU strains were mapped to 35000HP using nucleotide BLAST. The innermost ring showing the genomic positions represents the reference genome 35000HP. For clarity, each ring representing each strain is indicated by a different color. Positions covered by nucleotide BLAST are indicated as solid color, while positions not covered by nucleotide BLAST are indicated as white spaces. The gene coordinates of potential large-scale deletions are indicated.
Mentions: Compared to 35000HP, all the CU strains consistently contained ~20-kb deletion (HD1528 to HD1565) in a bacteriophage locus that is homologous to Pseudomonas aeruginosa bacteriophage B3 and five small deletions that ranged in size from 30–767 bp (Fig 2 and S2 Table). The class I strain HMC56 contained a 50-kb deletion (HD0897 to tRNA-Lys-1) in a region homologous to the H. influenzae ICEHin1056 integrative conjugative element (Fig 2 and S3 Table). All the class II strains contained 3 major deletions of 37 kb (HD0087 to HD0161), 35 kb (HD0478 to HD0495) and 50 kb (HD0897 to tRNA-Lys-1), which are homologous to Escherichia coli bacteriophage D108, Haemophilus bacteriophage SuMu, and H. influenzae ICEHin1056, respectively (Fig 2 and S4 Table). The class II strains also contained several deletions (between HD1528 and HD1618) in a region that is homologous to P. aeruginosa bacteriophage B3 (Fig 2 and S4 Table). All the GU strains also contained several other small deletions as listed in S3 and S4 Tables.

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