title: Haemophilus ducreyi Cutaneous Ulcer Strains Diverged from Both Class I and Class II Genital Ulcer Strains: Implications for Epidemiological Studies.
abstract: Haemophilus ducreyi has emerged as a major cause of cutaneous ulcers (CU) in yaws-endemic regions of the tropics in the South Pacific, South East Asia and Africa. H. ducreyi was once thought only to cause the genital ulcer (GU) disease chancroid; GU strains belong to 2 distinct classes, class I and class II. Using whole-genome sequencing of 4 CU strains from Samoa, 1 from Vanuatu and 1 from Papua New Guinea, we showed that CU strains diverged from the class I strain 35000HP and that one CU strain expressed β-lactamase. Recently, the Center for Disease Control and Prevention released the genomes of 11 additional CU strains from Vanuatu and Ghana; however, the evolutionary relationship of these CU strains to previously-characterized CU and GU strains is unknown.
  
  
  
  We performed phylogenetic analysis of 17 CU and 10 GU strains. Class I and class II GU strains formed two distinct clades. The class I strains formed two subclades, one containing 35000HP and HD183 and the other containing the remainder of the class I strains. Twelve of the CU strains formed a subclone under the class I 35000HP subclade, while 2 CU strains formed a subclone under the other class I subclade. Unexpectedly, 3 of the CU strains formed a subclone under the class II clade. Phylogenetic analysis of dsrA-hgbA-ncaA sequences yielded a tree similar to that of whole-genome phylogenetic tree.
  
  
  
  CU strains diverged from multiple lineages within both class I and class II GU strains. Multilocus sequence typing of dsrA-hgbA-ncaA could be reliably used for epidemiological investigation of CU and GU strains. As class II strains grow relatively poorly and are relatively more susceptible to vancomycin than class I strains, these findings have implications for methods to recover CU strains. Comparison of contemporary CU and GU isolates would help clarify the relationship between these entities.
authors.affiliation: Departments 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: Departments 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.|Departments of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Stanley M
authors.identifier: 0000-0003-3435-9911
authors.initials: SM
authors.lastname: Spinola
mesh_terms: D002602:Chancroid / Q000453:epidemiology / Q000382:microbiology*; D016680:Genome, Bacterial; D006191:Haemophilus ducreyi / Q000145:classification*; D006801:Humans; D010219:Papua New Guinea / Q000453:epidemiology; D010802:Phylogeny; D011114:Polynesia / Q000453:epidemiology; D012883:Skin Ulcer / Q000453:epidemiology / Q000382:microbiology*; D009514:Vanuatu / Q000453:epidemiology