Protein Palmitoylation Plays an Important Role in Trichomonas vaginalis Adherence

Yesica R Nievas,Ajay A Vashisht,Maria M Corvi,Sebastian Metz,Patricia J Johnson,James A Wohlschlegel,Natalia De Miguel

doi:10.1074/mcp.ra117.000018

Abstract

The flagellated protozoan parasite Trichomonas vaginalis is the etiologic agent of trichomoniasis, the most common non-viral sexually transmitted infection worldwide. As an obligate extracellular pathogen, adherence to epithelial cells is critical for parasite survival within the human host and a better understanding of this process is a prerequisite for the development of therapies to combat infection. In this sense, recent work has shown S-acylation as a key modification that regulates pathogenesis in different protozoan parasites. However, there are no reports indicating whether this post-translational modification is a mechanism operating in T. vaginalis In order to study the extent and function of S-acylation in T. vaginalis biology, we undertook a proteomic study to profile the full scope of S-acylated proteins in this parasite and reported the identification of 363 proteins involved in a variety of biological processes such as protein transport, pathogenesis related and signaling, among others. Importantly, treatment of parasites with the palmitoylation inhibitor 2-bromopalmitate causes a significant decrease in parasite: parasite aggregation as well as adherence to host cells suggesting that palmitoylation could be modifying proteins that are key regulators of Trichomonas vaginalis pathogenesis.

Highlights

The flagellated protozoan parasite Trichomonas vaginalis is the etiologic agent of trichomoniasis, the most common nonviral sexually transmitted infection worldwide with an estimated 276 million new cases annually [1, 2]
Recent works have unraveled the role of protein S-palmitoylation as a significant post-translational modification (PTM)1 that regulates invasion and motility in different protozoan parasites such as Plasmodium falciparum, Trypanosoma cruzi, Giardia lamblia, and Toxoplasma gondii [11, 12] as well as adherence to host cell in the fungus C. neoformans [13]
To analyze the role of protein palmitoylation in T. vaginalis, we undertook a proteomic study to profile the full complement of palmitoylated proteins in the parasite and reported here the identification of 363 proteins involved in a variety of biological processes including protein transport, pathogenesis related and signaling; among others

Summary

Introduction

The flagellated protozoan parasite Trichomonas vaginalis is the etiologic agent of trichomoniasis, the most common nonviral sexually transmitted infection worldwide with an estimated 276 million new cases annually [1, 2]. To the best of our knowledge, this is the first study to systematically identify and characterize palmitoylated proteins of Trichomonas parasites and demonstrate a key role regulating the function of proteins that modulate adherence, aggregation and the concomitant pathogenesis of T. vaginalis.

Results

Conclusion