Transcriptome Analysis of Intracellular Amastigotes of Clinical <i>Leishmania infantum</i> Lines from Therapeutic Failure Patients after Infection of Human Macrophages
Leishmaniasis is considered to be one of the most 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) lead...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-06-01
|
| Series: | Microorganisms |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-2607/10/7/1304 |
| _version_ | 1797416883465486336 |
|---|---|
| author | Raquel García-Hernández Ana Perea-Martínez José Ignacio Manzano Laura C. Terrón-Camero Eduardo Andrés-León Francisco Gamarro |
| author_facet | Raquel García-Hernández Ana Perea-Martínez José Ignacio Manzano Laura C. Terrón-Camero Eduardo Andrés-León Francisco Gamarro |
| author_sort | Raquel García-Hernández |
| collection | DOAJ |
| description | Leishmaniasis is considered to be one of the most 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) lead to an early obsolescence of treatments. Identification of the factors that contribute to TF and drug resistance in leishmaniasis will constitute a useful tool for establishing future strategies to control this disease. In this manuscript, we evaluated the transcriptomic changes in the intracellular amastigotes of the <i>Leishmania infantum</i> parasites isolated from patients with leishmaniasis and TF at 96 h post-infection of THP-1 cells. The adaptation of the parasites to their new environment leads to expression alterations in the genes involved mainly in the transport through cell membranes, energy and redox metabolism, and detoxification. Specifically, the gene that codes for the prostaglandin f2α synthase seems to be relevant in the pathogenicity and TF since it appears substantially upregulated in all the <i>L. infantum</i> lines. Overall, our results show that at the late infection timepoint, the transcriptome of the parasites undergoes significant changes that probably improve the survival of the <i>Leishmania</i> lines in the host cells, contributing to the TF phenotype as well as drug therapy evasion. |
| first_indexed | 2024-03-09T06:10:43Z |
| format | Article |
| id | doaj.art-a7c952d33e104d1c94040af97d49b8b4 |
| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-09T06:10:43Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-a7c952d33e104d1c94040af97d49b8b42023-12-03T11:58:41ZengMDPI AGMicroorganisms2076-26072022-06-01107130410.3390/microorganisms10071304Transcriptome Analysis of Intracellular Amastigotes of Clinical <i>Leishmania infantum</i> Lines from Therapeutic Failure Patients after Infection of Human MacrophagesRaquel García-Hernández0Ana Perea-Martínez1José Ignacio Manzano2Laura C. Terrón-Camero3Eduardo Andrés-León4Francisco Gamarro5Instituto de Parasitología y Biomedicina “López-Neyra”, IPBLN-CSIC, Parque Tecnológico de Ciencias de la Salud, Avda. del Conocimiento 17, Armilla, 18016 Granada, SpainInstituto de Parasitología y Biomedicina “López-Neyra”, IPBLN-CSIC, Parque Tecnológico de Ciencias de la Salud, Avda. del Conocimiento 17, Armilla, 18016 Granada, SpainInstituto de Parasitología y Biomedicina “López-Neyra”, IPBLN-CSIC, Parque Tecnológico de Ciencias de la Salud, Avda. del Conocimiento 17, Armilla, 18016 Granada, SpainInstituto de Parasitología y Biomedicina “López-Neyra”, IPBLN-CSIC, Parque Tecnológico de Ciencias de la Salud, Avda. del Conocimiento 17, Armilla, 18016 Granada, SpainInstituto de Parasitología y Biomedicina “López-Neyra”, IPBLN-CSIC, Parque Tecnológico de Ciencias de la Salud, Avda. del Conocimiento 17, Armilla, 18016 Granada, SpainInstituto de Parasitología y Biomedicina “López-Neyra”, IPBLN-CSIC, Parque Tecnológico de Ciencias de la Salud, Avda. del Conocimiento 17, Armilla, 18016 Granada, SpainLeishmaniasis is considered to be one of the most 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) lead to an early obsolescence of treatments. Identification of the factors that contribute to TF and drug resistance in leishmaniasis will constitute a useful tool for establishing future strategies to control this disease. In this manuscript, we evaluated the transcriptomic changes in the intracellular amastigotes of the <i>Leishmania infantum</i> parasites isolated from patients with leishmaniasis and TF at 96 h post-infection of THP-1 cells. The adaptation of the parasites to their new environment leads to expression alterations in the genes involved mainly in the transport through cell membranes, energy and redox metabolism, and detoxification. Specifically, the gene that codes for the prostaglandin f2α synthase seems to be relevant in the pathogenicity and TF since it appears substantially upregulated in all the <i>L. infantum</i> lines. Overall, our results show that at the late infection timepoint, the transcriptome of the parasites undergoes significant changes that probably improve the survival of the <i>Leishmania</i> lines in the host cells, contributing to the TF phenotype as well as drug therapy evasion.https://www.mdpi.com/2076-2607/10/7/1304<i>Leishmania infantum</i>intracellular amastigotesdrug-resistant parasitestherapeutic failure clinical parasiteshost infectiontranscriptomic analysis |
| spellingShingle | Raquel García-Hernández Ana Perea-Martínez José Ignacio Manzano Laura C. Terrón-Camero Eduardo Andrés-León Francisco Gamarro Transcriptome Analysis of Intracellular Amastigotes of Clinical <i>Leishmania infantum</i> Lines from Therapeutic Failure Patients after Infection of Human Macrophages Microorganisms <i>Leishmania infantum</i> intracellular amastigotes drug-resistant parasites therapeutic failure clinical parasites host infection transcriptomic analysis |
| title | Transcriptome Analysis of Intracellular Amastigotes of Clinical <i>Leishmania infantum</i> Lines from Therapeutic Failure Patients after Infection of Human Macrophages |
| title_full | Transcriptome Analysis of Intracellular Amastigotes of Clinical <i>Leishmania infantum</i> Lines from Therapeutic Failure Patients after Infection of Human Macrophages |
| title_fullStr | Transcriptome Analysis of Intracellular Amastigotes of Clinical <i>Leishmania infantum</i> Lines from Therapeutic Failure Patients after Infection of Human Macrophages |
| title_full_unstemmed | Transcriptome Analysis of Intracellular Amastigotes of Clinical <i>Leishmania infantum</i> Lines from Therapeutic Failure Patients after Infection of Human Macrophages |
| title_short | Transcriptome Analysis of Intracellular Amastigotes of Clinical <i>Leishmania infantum</i> Lines from Therapeutic Failure Patients after Infection of Human Macrophages |
| title_sort | transcriptome analysis of intracellular amastigotes of clinical i leishmania infantum i lines from therapeutic failure patients after infection of human macrophages |
| topic | <i>Leishmania infantum</i> intracellular amastigotes drug-resistant parasites therapeutic failure clinical parasites host infection transcriptomic analysis |
| url | https://www.mdpi.com/2076-2607/10/7/1304 |
| work_keys_str_mv | AT raquelgarciahernandez transcriptomeanalysisofintracellularamastigotesofclinicalileishmaniainfantumilinesfromtherapeuticfailurepatientsafterinfectionofhumanmacrophages AT anapereamartinez transcriptomeanalysisofintracellularamastigotesofclinicalileishmaniainfantumilinesfromtherapeuticfailurepatientsafterinfectionofhumanmacrophages AT joseignaciomanzano transcriptomeanalysisofintracellularamastigotesofclinicalileishmaniainfantumilinesfromtherapeuticfailurepatientsafterinfectionofhumanmacrophages AT lauracterroncamero transcriptomeanalysisofintracellularamastigotesofclinicalileishmaniainfantumilinesfromtherapeuticfailurepatientsafterinfectionofhumanmacrophages AT eduardoandresleon transcriptomeanalysisofintracellularamastigotesofclinicalileishmaniainfantumilinesfromtherapeuticfailurepatientsafterinfectionofhumanmacrophages AT franciscogamarro transcriptomeanalysisofintracellularamastigotesofclinicalileishmaniainfantumilinesfromtherapeuticfailurepatientsafterinfectionofhumanmacrophages |