Transcriptome analysis of intracellular amastigotes of clinical Leishmania infantum lines from therapeutic failure patients after infection of human macrophages. Homo sapiens

Leishmaniasis is considered as one of the neglected tropical diseases affecting humans and animals around the world. Due to the absence of an effective vaccine, current treatment is based on chemotherapy. However, the continuous appearance of drug resistance and therapeutic failure (TF) is leading to an early obsolescence of treatments. The identification of factors that contribute to TF and drug resistance in leishmaniasis will constitute a useful tool for the establishment of future strategies to control this disease. In this manuscript, we have evaluated the transcriptomic changes in intracellular amastigotes of Leishmania infantum parasites isolated from patients with leishmaniasis after 96 h post-infection of THP-1 cells. The adaption of parasites to its new environment led to alterations of gene expression involved mainly in transport through cell membranes, energy metabolism and redox metabolism, and detoxification. Specifically, the gene that codified the prostaglandin f2 synthase seems to be relevant for the pathogenicity and TF since it appeared differentially expressed in all the Leishmania infantum lines studied in the manuscript.Overall, these results show that in the late infection, the transcriptome of the parasites suffer significant changes that probably improve the survival of the Leishmania lines into the host cells contributing to the TF phenotype and drug therapy evasion.