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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

Maximum clade credibility tree from Bayesian molecular clock analysis of the CU and GU strains.The maximum clade credibility tree was generated using TreeAnnotator and visualized using FigTree v1.4.2. Values above the branches indicate posterior probability values in percentage. The blue bars indicate the 95% highest probability density of the inferred node ages. The posterior probability and 95% highest probability density were obtained from four independent runs of 10,000,000 iterations. The values on the time line indicate age in million years before present calculated using a mutation rate of 4.5 × 10−9 per site per year.
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pntd.0003918.g004: Maximum clade credibility tree from Bayesian molecular clock analysis of the CU and GU strains.The maximum clade credibility tree was generated using TreeAnnotator and visualized using FigTree v1.4.2. Values above the branches indicate posterior probability values in percentage. The blue bars indicate the 95% highest probability density of the inferred node ages. The posterior probability and 95% highest probability density were obtained from four independent runs of 10,000,000 iterations. The values on the time line indicate age in million years before present calculated using a mutation rate of 4.5 × 10−9 per site per year.

Mentions: To determine the approximate time to the MRCA of the CU strains, we performed a molecular clock analysis using the Bayesian method and the mutation rates proposed by Ochman et al. for calibration [25, 26]. The divergence time of the CU strains from the MRCA of the class I strains 35000HP and HD183 was estimated as 180,000 years ago (Fig 4). The divergence time of the CU strains, 35000HP, and HD183 from the MRCA of other class I strains was estimated as 450,000 years ago (Fig 4). The divergence time of class I strains from the MRCA of class II strains was estimated as 1.95 mya (Fig 4). Molecular clock analysis also showed that the CU strains began to diversify from each other around 27,000 years ago (Fig 4). Thus, CU strains appear to have recently diverged from class I GU strains.


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)

Maximum clade credibility tree from Bayesian molecular clock analysis of the CU and GU strains.The maximum clade credibility tree was generated using TreeAnnotator and visualized using FigTree v1.4.2. Values above the branches indicate posterior probability values in percentage. The blue bars indicate the 95% highest probability density of the inferred node ages. The posterior probability and 95% highest probability density were obtained from four independent runs of 10,000,000 iterations. The values on the time line indicate age in million years before present calculated using a mutation rate of 4.5 × 10−9 per site per year.
© Copyright Policy
Related In: Results  -  Collection

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

pntd.0003918.g004: Maximum clade credibility tree from Bayesian molecular clock analysis of the CU and GU strains.The maximum clade credibility tree was generated using TreeAnnotator and visualized using FigTree v1.4.2. Values above the branches indicate posterior probability values in percentage. The blue bars indicate the 95% highest probability density of the inferred node ages. The posterior probability and 95% highest probability density were obtained from four independent runs of 10,000,000 iterations. The values on the time line indicate age in million years before present calculated using a mutation rate of 4.5 × 10−9 per site per year.
Mentions: To determine the approximate time to the MRCA of the CU strains, we performed a molecular clock analysis using the Bayesian method and the mutation rates proposed by Ochman et al. for calibration [25, 26]. The divergence time of the CU strains from the MRCA of the class I strains 35000HP and HD183 was estimated as 180,000 years ago (Fig 4). The divergence time of the CU strains, 35000HP, and HD183 from the MRCA of other class I strains was estimated as 450,000 years ago (Fig 4). The divergence time of class I strains from the MRCA of class II strains was estimated as 1.95 mya (Fig 4). Molecular clock analysis also showed that the CU strains began to diversify from each other around 27,000 years ago (Fig 4). Thus, CU strains appear to have recently diverged from class I GU strains.

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