title: Haemophilus ducreyi Cutaneous Ulcer Strains Are Nearly Identical to Class I Genital Ulcer Strains.
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?
  
  
  RESULTS
  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
  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.
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Dharanesh
authors.initials: D
authors.lastname: Gangaiah
authors.affiliation: Department of Biology, Allegheny College, Meadville, Pennsylvania, United States of America.
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Webb
authors.affiliation: Department of Biology, Allegheny College, Meadville, Pennsylvania, United States of America.
authors.forename: Tricia L
authors.initials: TL
authors.lastname: Humphreys
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Kate R
authors.initials: KR
authors.lastname: Fortney
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Toh
authors.affiliation: Genomics Core, Tufts University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Albert
authors.initials: A
authors.lastname: Tai
authors.affiliation: Laboratory Reference and Research Branch, Division of STD Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD and Tuberculosis Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Samantha S
authors.initials: SS
authors.lastname: Katz
authors.affiliation: Laboratory Reference and Research Branch, Division of STD Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD and Tuberculosis Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Allan
authors.initials: A
authors.lastname: Pillay
authors.affiliation: Laboratory Reference and Research Branch, Division of STD Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD and Tuberculosis Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Cheng-Yen
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Department of Microbiology, Auckland District Health Board, Auckland, New Zealand.
authors.forename: Sally A
authors.initials: SA
authors.lastname: Roberts
authors.affiliation: The Center for Microbial Pathogenesis in the Research Institute at Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus, Ohio, United States of America; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio, United States of America.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Munson
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America; Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States of America; Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States of America; The Center for Immunobiology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Stanley M
authors.initials: SM
authors.lastname: Spinola
mesh_terms: D000293:Adolescent; D000349:Africa; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002602:Chancroid / Q000382:microbiology*; D002648:Child; D024881:Drug Resistance, Bacterial; D019143:Evolution, Molecular; D005260:Female; D006191:Haemophilus ducreyi / Q000145:classification / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010802:Phylogeny; D060737:Reproductive Tract Infections / Q000382:microbiology*; D012883:Skin Ulcer / Q000382:microbiology*; D015001:Yaws / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents