PXD031912

PXD031912 is an original dataset announced via ProteomeXchange.

Title	In-depth proteomics analysis of a Leishmania infantum strain selected in vitro for miltefosine resistance
Description	Visceral Leishmaniasis (VL) is a neglected disease caused Leishmania parasites. Although significant morbidity and mortality in tropical and subtropical regions of the world are associated to VL, low investment for developing new treatment measures is chronic. Moreover, resistance and treatment failure are increasing for the main medications, but the emergence of resistance phenotypes is poorly understood at the protein level. Here, we analyzed the development of resistance to miltefosine upon experimental selection in a L. infantum strain. Time to miltefosine resistance emergence was ~six months and label-free quantitative mass-spectrometry-based proteomics analyses revealed that this process involves a remodeling of components of the membrane and mitochondrion, with significant increase in oxidative phosphorylation complexes, particularly on complex IV and ATP synthase, accompanied by increased energy metabolism mainly dependent on β-oxidation of fatty acids. Proteins canonically involved in ROS detoxification did not contribute to the resistant process whereas sterol biosynthesis enzymes could have a role in this development. Also, changes in the abundance of proteins known to be involved in miltefosine resistance such as ABC transporters and phospholipid transport ATPase were detected. Together, our data show a more complete picture of the elements that make up the miltefosine resistance phenotype in L. infantum.
HostingRepository	PRIDE
AnnounceDate	2022-05-20
AnnouncementXML	Submission_2022-05-20_07:43:55.380.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jacek Wisniewski
SpeciesList	scientific name: Leishmania infantum; NCBI TaxID: 5671;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-02-28 01:11:00	ID requested
⏵ 1	2022-05-20 07:43:57	announced

Saboia-Vahia L, Cuervo P, Wi, ś, niewski JR, Dias-Lopes G, Pinho N, Padr, ó, n G, de Pilla Varotti F, Murta SMF, . Proteomes, 10(2):(2022) [pubmed]

submitter keyword: Leishmania infantum

miltefosine resistance

quantitative proteomics

FASP

mass spectrometry

oxidative phosphorylation, TCA cycle, fatty acid β-oxidation, cytochrome c oxidase, ATP synthase.

Jacek R Wisniewski
contact affiliation	Max Planck Intitute of Biochemistry
contact email	jwisniew@biochem.mpg.de
lab head
Jacek Wisniewski
contact affiliation	Proteomics
contact email	jwisniew@biochem.mpg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD031912
     1. Label: PRIDE project
     2. Name: In-depth proteomics analysis of a Leishmania infantum strain selected in vitro for miltefosine resistance