Physiological and proteomic profiles of Trypanosoma brucei rhodesiense parasite isolated from suramin responsive and non-responsive HAT patients in Busoga, Uganda
Human African Trypanosomiasis (HAT) is a disease of major economic importance in Sub-Saharan Africa. The HAT is caused by Trypanosoma brucei rhodesiense (Tbr) parasite in eastern and southern Africa, with suramin as drug of choice for treatment of early stage of the disease. Suramin treatment failur...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-04-01
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| Series: | International Journal for Parasitology: Drugs and Drug Resistance |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S221132072100004X |
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| author | Catherine N. Mutuku Rosemary Bateta Martin K. Rono James M. Njunge Erick O. Awuoche Kariuki Ndung'u Clarence M. Mang'era Modesta O. Akoth Vincent O. Adung'a Bartholomew N. Ondigo Paul O. Mireji |
| author_facet | Catherine N. Mutuku Rosemary Bateta Martin K. Rono James M. Njunge Erick O. Awuoche Kariuki Ndung'u Clarence M. Mang'era Modesta O. Akoth Vincent O. Adung'a Bartholomew N. Ondigo Paul O. Mireji |
| author_sort | Catherine N. Mutuku |
| collection | DOAJ |
| description | Human African Trypanosomiasis (HAT) is a disease of major economic importance in Sub-Saharan Africa. The HAT is caused by Trypanosoma brucei rhodesiense (Tbr) parasite in eastern and southern Africa, with suramin as drug of choice for treatment of early stage of the disease. Suramin treatment failures has been observed among HAT patients in Tbr foci in Uganda. In this study, we assessed Tbr parasite strains isolated from HAT patients responsive (Tbr EATRO-232) and non-responsive (Tbr EATRO-734) to suramin treatment in Busoga, Uganda for 1) putative role of suramin resistance in the treatment failure 2) correlation of suramin resistance with Tbr pathogenicity and 3) proteomic pathways underpinning the potential suramin resistance phenotype in vivo. We first assessed suramin response in each isolate by infecting male Swiss white mice followed by treatment using a series of suramin doses. We then assessed relative pathogenicity of the two Tbr isolates by assessing changes pathogenicity indices (prepatent period, survival and mortality). We finally isolated proteins from mice infected by the isolates, and assessed their proteomic profiles using mass spectrometry. We established putative resistance to 2.5 mg/kg suramin in the parasite Tbr EATRO-734. We established that Tbr EATRO-734 proliferated slower and has significantly enriched pathways associated with detoxification and metabolism of energy and drugs relative to Tbr EATRO-232. The Tbr EATRO-734 also has more abundantly expressed mitochondrion proteins and enzymes than Tbr EATRO-232. The suramin treatment failure may be linked to the relatively higher resistance to suramin in Tbr EATRO-734 than Tbr EATRO-232, among other host and parasite specific factors. However, the Tbr EATRO-734 appears to be less pathogenic than Tbr EATRO-232, as evidenced by its lower rate of parasitaemia. The Tbr EATRO-734 putatively surmount suramin challenges through induction of energy metabolism pathways. These cellular and molecular processes may be involved in suramin resistance in Tbr. |
| first_indexed | 2024-12-14T20:54:42Z |
| format | Article |
| id | doaj.art-02d13e9ccdac4824b2638eb0864657d7 |
| institution | Directory Open Access Journal |
| issn | 2211-3207 |
| language | English |
| last_indexed | 2024-12-14T20:54:42Z |
| publishDate | 2021-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | International Journal for Parasitology: Drugs and Drug Resistance |
| spelling | doaj.art-02d13e9ccdac4824b2638eb0864657d72022-12-21T22:47:42ZengElsevierInternational Journal for Parasitology: Drugs and Drug Resistance2211-32072021-04-01155767Physiological and proteomic profiles of Trypanosoma brucei rhodesiense parasite isolated from suramin responsive and non-responsive HAT patients in Busoga, UgandaCatherine N. Mutuku0Rosemary Bateta1Martin K. Rono2James M. Njunge3Erick O. Awuoche4Kariuki Ndung'u5Clarence M. Mang'era6Modesta O. Akoth7Vincent O. Adung'a8Bartholomew N. Ondigo9Paul O. Mireji10Biotechnology Research Institute, Kenya Agricultural and Livestock Research Organization, P.O. Box 362, Kikuyu, Kenya; Department of Biochemistry and Molecular Biology, Egerton University, P.O. Box 536, Njoro, KenyaBiotechnology Research Institute, Kenya Agricultural and Livestock Research Organization, P.O. Box 362, Kikuyu, Kenya; Corresponding author.Centre for Geographic Medicine Research – Coast, Kenya Medical Research Institute, PO Box 230–80108 Kilifi, KenyaCentre for Geographic Medicine Research – Coast, Kenya Medical Research Institute, PO Box 230–80108 Kilifi, KenyaDepartment of Biological Sciences, School of Pure and Applied Science, Meru University of Science and Technology, Meru, KenyaBiotechnology Research Institute, Kenya Agricultural and Livestock Research Organization, P.O. Box 362, Kikuyu, KenyaDepartment of Biochemistry and Molecular Biology, Egerton University, P.O. Box 536, Njoro, KenyaBiotechnology Research Institute, Kenya Agricultural and Livestock Research Organization, P.O. Box 362, Kikuyu, Kenya; Department of Biochemistry and Molecular Biology, Egerton University, P.O. Box 536, Njoro, KenyaDepartment of Biochemistry and Molecular Biology, Egerton University, P.O. Box 536, Njoro, KenyaDepartment of Biochemistry and Molecular Biology, Egerton University, P.O. Box 536, Njoro, KenyaBiotechnology Research Institute, Kenya Agricultural and Livestock Research Organization, P.O. Box 362, Kikuyu, Kenya; Centre for Geographic Medicine Research – Coast, Kenya Medical Research Institute, PO Box 230–80108 Kilifi, Kenya; Corresponding author. Biotechnology Research Institute, Kenya Agricultural and Livestock Research Organization, P.O. Box 362, Kikuyu, Kenya.Human African Trypanosomiasis (HAT) is a disease of major economic importance in Sub-Saharan Africa. The HAT is caused by Trypanosoma brucei rhodesiense (Tbr) parasite in eastern and southern Africa, with suramin as drug of choice for treatment of early stage of the disease. Suramin treatment failures has been observed among HAT patients in Tbr foci in Uganda. In this study, we assessed Tbr parasite strains isolated from HAT patients responsive (Tbr EATRO-232) and non-responsive (Tbr EATRO-734) to suramin treatment in Busoga, Uganda for 1) putative role of suramin resistance in the treatment failure 2) correlation of suramin resistance with Tbr pathogenicity and 3) proteomic pathways underpinning the potential suramin resistance phenotype in vivo. We first assessed suramin response in each isolate by infecting male Swiss white mice followed by treatment using a series of suramin doses. We then assessed relative pathogenicity of the two Tbr isolates by assessing changes pathogenicity indices (prepatent period, survival and mortality). We finally isolated proteins from mice infected by the isolates, and assessed their proteomic profiles using mass spectrometry. We established putative resistance to 2.5 mg/kg suramin in the parasite Tbr EATRO-734. We established that Tbr EATRO-734 proliferated slower and has significantly enriched pathways associated with detoxification and metabolism of energy and drugs relative to Tbr EATRO-232. The Tbr EATRO-734 also has more abundantly expressed mitochondrion proteins and enzymes than Tbr EATRO-232. The suramin treatment failure may be linked to the relatively higher resistance to suramin in Tbr EATRO-734 than Tbr EATRO-232, among other host and parasite specific factors. However, the Tbr EATRO-734 appears to be less pathogenic than Tbr EATRO-232, as evidenced by its lower rate of parasitaemia. The Tbr EATRO-734 putatively surmount suramin challenges through induction of energy metabolism pathways. These cellular and molecular processes may be involved in suramin resistance in Tbr.http://www.sciencedirect.com/science/article/pii/S221132072100004XSuraminDrug resistanceDrug sensitive, Trypanosoma brucei rhodesience |
| spellingShingle | Catherine N. Mutuku Rosemary Bateta Martin K. Rono James M. Njunge Erick O. Awuoche Kariuki Ndung'u Clarence M. Mang'era Modesta O. Akoth Vincent O. Adung'a Bartholomew N. Ondigo Paul O. Mireji Physiological and proteomic profiles of Trypanosoma brucei rhodesiense parasite isolated from suramin responsive and non-responsive HAT patients in Busoga, Uganda International Journal for Parasitology: Drugs and Drug Resistance Suramin Drug resistance Drug sensitive, Trypanosoma brucei rhodesience |
| title | Physiological and proteomic profiles of Trypanosoma brucei rhodesiense parasite isolated from suramin responsive and non-responsive HAT patients in Busoga, Uganda |
| title_full | Physiological and proteomic profiles of Trypanosoma brucei rhodesiense parasite isolated from suramin responsive and non-responsive HAT patients in Busoga, Uganda |
| title_fullStr | Physiological and proteomic profiles of Trypanosoma brucei rhodesiense parasite isolated from suramin responsive and non-responsive HAT patients in Busoga, Uganda |
| title_full_unstemmed | Physiological and proteomic profiles of Trypanosoma brucei rhodesiense parasite isolated from suramin responsive and non-responsive HAT patients in Busoga, Uganda |
| title_short | Physiological and proteomic profiles of Trypanosoma brucei rhodesiense parasite isolated from suramin responsive and non-responsive HAT patients in Busoga, Uganda |
| title_sort | physiological and proteomic profiles of trypanosoma brucei rhodesiense parasite isolated from suramin responsive and non responsive hat patients in busoga uganda |
| topic | Suramin Drug resistance Drug sensitive, Trypanosoma brucei rhodesience |
| url | http://www.sciencedirect.com/science/article/pii/S221132072100004X |
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