Extensive Genetic Diversity, Unique Population Structure and Evidence of Genetic Exchange in the Sexually Transmitted Parasite Trichomonas vaginalis

Melissa D Conrad,Susan Blank,Nancy Malla,Julia A Schillinger,William E Secor,Pier Luigi Fiori,Rossana Arroyo,Jorge Gonzalez,Mohan Lal Dubey,Andrew W Gorman,Jane M Carlton,Elodie Ghedin

doi:10.1371/journal.pntd.0001573

Abstract

Background Trichomonas vaginalis is the causative agent of human trichomoniasis, the most common non-viral sexually transmitted infection world-wide. Despite its prevalence, little is known about the genetic diversity and population structure of this haploid parasite due to the lack of appropriate tools. The development of a panel of microsatellite makers and SNPs from mining the parasite's genome sequence has paved the way to a global analysis of the genetic structure of the pathogen and association with clinical phenotypes.Methodology/Principal FindingsHere we utilize a panel of T. vaginalis-specific genetic markers to genotype 235 isolates from Mexico, Chile, India, Australia, Papua New Guinea, Italy, Africa and the United States, including 19 clinical isolates recently collected from 270 women attending New York City sexually transmitted disease clinics. Using population genetic analysis, we show that T. vaginalis is a genetically diverse parasite with a unique population structure consisting of two types present in equal proportions world-wide. Parasites belonging to the two types (type 1 and type 2) differ significantly in the rate at which they harbor the T. vaginalis virus, a dsRNA virus implicated in parasite pathogenesis, and in their sensitivity to the widely-used drug, metronidazole. We also uncover evidence of genetic exchange, indicating a sexual life-cycle of the parasite despite an absence of morphologically-distinct sexual stages.Conclusions/SignificanceOur study represents the first robust and comprehensive evaluation of global T. vaginalis genetic diversity and population structure. Our identification of a unique two-type structure, and the clinically relevant phenotypes associated with them, provides a new dimension for understanding T. vaginalis pathogenesis. In addition, our demonstration of the possibility of genetic exchange in the parasite has important implications for genetic research and control of the disease.

Highlights

Trichomoniasis is the most common non-viral sexually transmitted infection (STI) world-wide
Research on T. vaginalis genetic diversity has been limited by a lack of appropriate genotyping tools
To assay the global diversity and population structure of T. vaginalis, we present here analysis of 235 T. vaginalis isolates from ten world-wide regions in Mexico, Chile, India, Australia, Papua New Guinea, Italy, Africa and the United States, including 19 clinical isolates recently collected from 270 women attending New York City sexually transmitted disease (STD) clinics

Summary

Introduction

Trichomoniasis is the most common non-viral sexually transmitted infection (STI) world-wide. Symptoms include malodorous vaginal discharge, vulval irritation and inflammation, and punctate microhemorrhages on the cervix known as ‘strawberry cervix’ [7]. Trichomoniasis has been associated with severe reproductive health sequelae in both sexes, including, pelvic inflammatory disease [9] and adverse pregnancy outcomes [10,11] in women, and prostatitis, infertility, and an increased incidence of aggressive prostate cancers in men [8,12]. Trichomonas vaginalis is the causative agent of human trichomoniasis, the most common non-viral sexually transmitted infection world-wide. Little is known about the genetic diversity and population structure of this haploid parasite due to the lack of appropriate tools. The development of a panel of microsatellite makers and SNPs from mining the parasite’s genome sequence has paved the way to a global analysis of the genetic structure of the pathogen and association with clinical phenotypes

Methods

Results

Discussion

Conclusion