NEW YORK (GenomeWeb) – An international team led by investigators in Switzerland, Germany, and Spain used genomics to investigate the roots of syphilis pandemics over the past few centuries.
The researchers noted that syphilis cases — caused by Treponema pallidum bacteria in the pallidum sub-species — began spreading across Europe and beyond in the late 1400s, after a flare-up in hostilities during the War of Naples. The past few decades have seen a resurgence in the disease despite available antibiotic treatments and ongoing penicillin-sensitivity, prompting the investigators to do whole-genome sequencing on dozens of T. pallidum subsp. pallidum isolates collected from more than a dozen countries.
Compared with T. pallidum subsp. pertenue and T. pallidum subsp. endicum bacteria behind related conditions called yaws and bejel, the team found that the syphilis-causing microbes can be phylogenetically traced back to a shared common ancestor that was present after the 15th century. During the 20th century, after the advent of antibiotics, a cluster within this lineage called SS14-omega, appears to have become increasingly common and resistant to the macrolide antibiotic azithromycin.
"Through comparative genome analyses and phylogenetic reconstruction, we shed light on the evolutionary history of [T. pallidum subsp. pallidum] and identify epidemiologically relevant haplotypes," senior author Homayoun Bagheri, an evolutionary biology and environmental studies researcher at the University of Zurich, and his co-authors wrote in their study, published yesterday in Nature Microbiology.
The researchers used DNA capture with the Agilent SureSelect array to enrich for T. pallidum genetic material in 70 samples originating in more than a dozen countries and spanning from 1912 to 2013. Using the Illumina HiSeq 2500, they then performed whole-genome sequencing on the set, which included 52 syphilis swabs collected in 2012 and 2013, along with 18 historic syphilis, yaws, or bejel samples that have been grown in rabbits.
The team put together four de novo genome sequence assemblies for four syphilis samples and one sample of yaws, while its broader genomic analysis included the 28 samples where sequences were successfully generated for at least 80 percent of the genome.
Apart from a deletion affecting a potential virulence gene in the yaws isolate genome, the researchers did not uncover any notable structural changes in the assemblies. Their phylogenetic analysis of the newly sequenced isolates and 11 T. pallidum genomes sequenced previously supported a split between the pallidum subspecies and the subspecies that cause yaws or bejel.
One clade in the syphilis-causing T. pallidum subsp. pallidum lineage was mainly comprised of North American samples that had been obtained between 1912 and the mid-1980s. A second clade spanned several continents, was linked to infections from the 1950s to 2013, and contains the macrolide-resistant cluster that became common recently.
"Our phylogenetic reconstruction indicates that all [T. pallidum subsp. pallidum] samples examined to date share a common ancestor that was infecting populations in the 1700s, within the early centuries of the modern era, and that was successful in leaving descendants until today," the author wrote, adding that "[t]he relatively recent phylogenetic divergence of the SS14-omega cluster and its global presence point to the emergence of a pandemic azithromycin-resistant cluster."