Syphillis, a sexually transmitted infection, affects more than
10 million cases annually. It has plagued humankind for over 500 years.
After the first
reported outbreaks struck Europe in 1495, the disease spread rapidly to
other continents and swelled to a global pandemic. When treatment with
the antibiotic penicillin became available in the mid-twentieth century,
infection rates started to decrease dramatically.
‘The current syphilis infections are predominantly due to antibiotic-resistant strains from a pandemic cluster.’
infection with the bacteria Treponema pallidum
(TPA) has been re-emerging globally in the last few decades. Yet the reason for the
resurgence of this sexually transmitted infection remains poorly
New techniques to analyze an old disease
According to the authors of the paper, little is known about the
patterns of genetic diversity in current infections or the evolutionary
origins of the disease. Because clinical samples from syphilis patients
only contain low quantities of treponemal DNA and the pathogen is
difficult to culture in the laboratory, researchers from the University
of Zurich decided in 2013 to apply DNA capture and whole-genome
sequencing techniques, as used by colleagues at the University of
Tübingen, to ancient DNA samples.
The team collected 70 clinical and
laboratory samples of syphilis, yaws, and bejel infections from 13
countries spread across the globe. Like syphilis bacteria, the closely
related subspecies Treponema pallidum
(TPE) and Treponema pallidum
(TEN), which cause yaws and bejel, are transmitted through skin contact and show similar clinical manifestations.
By using genome-wide data, the researchers were able to reconstruct a
phylogenetic tree showing a clear separation between the TPA lineage
and the TPE/TEN lineage.
"There have been many questions regarding the
origin of syphilis since its appearance on the world stage 500 years
ago. By combining an evolutionary and an epidemiological approach, we
were able to decipher the genetic relation between strains infecting
individuals today, and also trace the emergence of a pandemic cluster
with high frequency of antibiotic resistance", says Homayoun C. Bagheri,
former professor at the UZH Institute for Evolutionary Biology and
Current syphilis infections predominantly due to resistant strains from a pandemic cluster
The genomic analyses show the emergence of a pandemic cluster named
SS14-Ω, which is present in contemporary infections around the globe and
distinct from the cluster comprising the well-studied Nichols reference
strain. "Our findings highlight the need to study more extensively the
predominant strain type in the contemporary epidemic", states Natasha
Arora, researcher at the Zurich Institute of Forensic Medicine and first
author of the study published in Nature Microbiology
An evolutionary finding of epidemiological relevance is that the
SS14-Ω cluster originated from a strain ancestor in the mid-20th century
- after the discovery of antibiotics. The worrying aspect of this
pandemic cluster is its high resistance to azithromycin, a second-line
drug that is widely used to treat sexually transmitted infections.
Natasha Arora adds: "The good news is that, so far, no Treponema strains
have been detected that are resistant to penicillin, the first-line
antibiotic for syphilis treatment."
Co-author Philipp Bosshard from the University Hospital Zurich is
continuing to collect Swiss patient samples in order to further study
the clinical aspects of the work. The researchers are convinced that
this type of analysis will open new opportunities to develop a
comprehensive understanding of the epidemiology of syphilis - a
devastating disease that persists to this day, despite the availability