Proteomics and Leishmaniasis: Potential Clinical Applications

Abstract

Leishmaniases are diseases caused by protozoan parasites of the genus Leishmania. They are endemic in 98 countries, affect around 12 million people worldwide and may present several distinct clinical forms. Unfortunately, there are only a few drugs available for treatment of leishmaniasis, which are toxic and not always effective. Different parasite species and different clinical forms require optimization of the treatment or more specific therapies, which are not available. The emergence of resistance is also a matter of concern. Besides, diagnosis can sometimes be complicated due to atypical manifestations and associations with other pathologies. In this review, proteomic data are presented and discussed in terms of their application in important issues in leishmaniasis such as parasite resistance to chemotherapy, diagnosis of active disease in patients and dogs, markers for different clinical forms, identification of virulence factors, and their potential use in vaccination. It is shown that proteomics has contributed to the discovery of potential biomarkers for prognosis, diagnosis, therapeutics, monitoring of disease progression, treatment follow‐up and identification of vaccine candidates for specific diseases. However, the authors believe its capabilities have not yet been fully explored for routine clinical analysis for several reasons, which will be presented in this review.

Translational profiling of macrophages infected with Leishmania donovani identifies mTOR- and eIF4A-sensitive immune-related transcripts

“…Interestingly, eIF4A inhibitors have been shown to act as dual-targeting therapeutic agents by interfering with both pathogen and host eIF4A activity during malaria, an infection caused by protozoan parasites of the genus Plasmodium [12]. Of note, a strain of L. donovani resistant to miltefosine had increased levels of eIF4A [63] and high-throughput screenings identified Leishmania eIF4A as a potential druggable target [64][65][66][67]. Collectively, our data along with previous studies warrant further investigation on the potential of targeting eIF4A-dependent host and parasite mRNA translation to treat L. donovani infections.…”

The Experimental Proteome of Leishmania infantum Promastigote and Its Usefulness for Improving Gene Annotations

“…In parallel to the advances in sequencing technologies, proteomics methodologies are achieving unprecedented levels of sensitivity, and novel MS-based experimental approaches have become the method of choice for the analysis of complex protein mixtures such as cells, tissues, and even whole organisms. In particular, several proteomic technologies are being used to study diverse aspects of Leishmania biology such as parasite development, virulence, and drug resistance [17]. Thus, proteomics approaches have been used to determine differential patterns of protein expression between the promastigote and amastigote stages in Leishmania mexicana [18], L. infantum [19], and L. donovani [20], among others.…”

Applied Proteomics in ‘One Health’

“…The disease is presented with a wide clinical spectrum, depending on the protozoan species involved and the genetic background and immunological status of the host. There are three main clinical forms of the infection: visceral (the most grave form), cutaneous (the most common form) and mucocutaneous [ 15 , 202 ].…”