Pharmacological Inhibition of the Vacuolar ATPase in Bloodstream-Form Trypanosoma brucei Rescues Genetic Knockdown of Mitochondrial Gene Expression

Claudia Schaffner-Barbero; Migla Miskinyte; Jaspreet Singh Grewal; Achim Schnaufer

doi:10.1128/AAC.02268-17

Pharmacological Inhibition of the Vacuolar ATPase in Bloodstream-Form Trypanosoma brucei Rescues Genetic Knockdown of Mitochondrial Gene Expression

Claudia Schaffner-Barbero, Migla Miskinyte, Jaspreet Singh Grewal, Achim Schnaufer

School of Biological Sciences

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

Trypanosomatid parasites cause diseases in humans and livestock. It was reported that partial inhibition of the vacuolar ATPase (V-ATPase) affects dependence of Trypanosoma brucei on its mitochondrial genome (kDNA), a target of the anti-trypanosomatid drug isometamidium. Here we report that V-ATPase inhibition with bafilomycin A1 (BafA) provides partial resistance to genetic knockdown of mitochondrial gene expression. BafA does not promote long-term survival after kDNA loss, but in its presence, isometamidium causes less damage to kDNA.

Original language	English
Number of pages	7
Journal	Antimicrobial Agents and Chemotherapy
Volume	62
Issue number	9
Early online date	18 Jun 2018
DOIs	https://doi.org/10.1128/AAC.02268-17
Publication status	Published - 27 Aug 2018

Keywords / Materials (for Non-textual outputs)

F1Fo-ATPase
RNA editing
Trypanosoma
V-ATPase
bafilomycin
kDNA
kinetoplast
mitochondria
vacuoles

Access to Document

10.1128/AAC.02268-17

Antimicrob. Agents Chemother.-2018-Schaffner-Barbero-AAC.02268-17Accepted author manuscript, 2.03 MB
Pharmacological Inhibition PUB OA CC BY e02268-17.full
© 2018 Schaffner-Barbero et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
Final published version, 1.26 MBLicence: Creative Commons: Attribution (CC-BY)

Mitochondrial biogenesis and function in trypanosomes
Schnaufer, A.
MRC
1/04/14 → 30/06/21
Project: Research

Achim Schnaufer
- School of Biological Sciences - Personal Chair of Parasite and Mitochondrial Biology
Person: Academic: Research Active

Cite this

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title = "Pharmacological Inhibition of the Vacuolar ATPase in Bloodstream-Form Trypanosoma brucei Rescues Genetic Knockdown of Mitochondrial Gene Expression",

abstract = "Trypanosomatid parasites cause diseases in humans and livestock. It was reported that partial inhibition of the vacuolar ATPase (V-ATPase) affects dependence of Trypanosoma brucei on its mitochondrial genome (kDNA), a target of the anti-trypanosomatid drug isometamidium. Here we report that V-ATPase inhibition with bafilomycin A1 (BafA) provides partial resistance to genetic knockdown of mitochondrial gene expression. BafA does not promote long-term survival after kDNA loss, but in its presence, isometamidium causes less damage to kDNA.",

keywords = "F1Fo-ATPase, RNA editing, Trypanosoma, V-ATPase, bafilomycin, kDNA, kinetoplast, mitochondria, vacuoles",

author = "Claudia Schaffner-Barbero and Migla Miskinyte and Grewal, {Jaspreet Singh} and Achim Schnaufer",

note = "I need to wait and upload the final PDF when this is available online 19/07/2018 EN",

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doi = "10.1128/AAC.02268-17",

language = "English",

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journal = "Antimicrobial Agents and Chemotherapy",

issn = "0066-4804",

publisher = "American Society for Microbiology",

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TY - JOUR

T1 - Pharmacological Inhibition of the Vacuolar ATPase in Bloodstream-Form Trypanosoma brucei Rescues Genetic Knockdown of Mitochondrial Gene Expression

AU - Schaffner-Barbero, Claudia

AU - Miskinyte, Migla

AU - Grewal, Jaspreet Singh

AU - Schnaufer, Achim

N1 - I need to wait and upload the final PDF when this is available online 19/07/2018 EN

PY - 2018/8/27

Y1 - 2018/8/27

N2 - Trypanosomatid parasites cause diseases in humans and livestock. It was reported that partial inhibition of the vacuolar ATPase (V-ATPase) affects dependence of Trypanosoma brucei on its mitochondrial genome (kDNA), a target of the anti-trypanosomatid drug isometamidium. Here we report that V-ATPase inhibition with bafilomycin A1 (BafA) provides partial resistance to genetic knockdown of mitochondrial gene expression. BafA does not promote long-term survival after kDNA loss, but in its presence, isometamidium causes less damage to kDNA.

AB - Trypanosomatid parasites cause diseases in humans and livestock. It was reported that partial inhibition of the vacuolar ATPase (V-ATPase) affects dependence of Trypanosoma brucei on its mitochondrial genome (kDNA), a target of the anti-trypanosomatid drug isometamidium. Here we report that V-ATPase inhibition with bafilomycin A1 (BafA) provides partial resistance to genetic knockdown of mitochondrial gene expression. BafA does not promote long-term survival after kDNA loss, but in its presence, isometamidium causes less damage to kDNA.

KW - F1Fo-ATPase

KW - RNA editing

KW - Trypanosoma

KW - V-ATPase

KW - bafilomycin

KW - kDNA

KW - kinetoplast

KW - mitochondria

KW - vacuoles

U2 - 10.1128/AAC.02268-17

DO - 10.1128/AAC.02268-17

M3 - Article

C2 - 29914945

SN - 0066-4804

VL - 62

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

IS - 9

ER -

Pharmacological Inhibition of the Vacuolar ATPase in Bloodstream-Form Trypanosoma brucei Rescues Genetic Knockdown of Mitochondrial Gene Expression

Abstract / Description of output

Keywords / Materials (for Non-textual outputs)

Access to Document

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Projects

Mitochondrial biogenesis and function in trypanosomes

Profiles

Achim Schnaufer

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