Abstract
BackgroundHaemophilus 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.Methodology/Principal FindingsWe 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.Conclusions/SignificanceCU 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.
Highlights
Haemophilus ducreyi causes chancroid, a sexually transmitted disease that manifests as genital ulcers (GU) and regional lymphadenitis in adults
Cutaneous ulcers (CU) in children in yaws-endemic regions have long been attributed to Treponema pallidum subsp. pertenue; recent studies show that Haemophilus ducreyi is an important cause of cutaneous ulcers (CU) in these regions
We previously showed that CU strains obtained from Samoa, Vanuatu and Papua New Guinea are genetically almost identical to class 1 GU strains
Summary
Haemophilus ducreyi causes chancroid, a sexually transmitted disease that manifests as genital ulcers (GU) and regional lymphadenitis in adults. Recent studies conducted in the yaws-endemic regions of the South Pacific islands and equatorial Africa show that H. ducreyi has emerged as an important cause of nonsexually transmitted cutaneous ulcers (CU) in children [1, 8,9,10,11,12]. In studies conducted in yaws-endemic villages on Vanuatu and Lihir Island of Papua New Guinea, H. ducreyi was detected in 39% to 60% of all skin ulcers, while Treponema pallidum subspecies pertenue, the etiologic agent of yaws, which was thought to be the major cause of CU, was detected in 15% to 34% of skin ulcers, respectively [8, 10, 11]. The Center for Disease Control and Prevention released the genomes of 11 additional CU strains from Vanuatu and Ghana; the evolutionary relationship of these CU strains to previously-characterized CU and GU strains is unknown
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