Characterization of a subunit of the outer dynein arm docking complex necessary for correct flagellar assembly in Leishmania donovani
Authors: Meike Thiel
Simone Harder
Iris Bruchhaus
Joachim Clos
Journal: PLoS neglected tropical diseases (2010)
Discipline: IMMUNOLOGY
Keywords: Leishmania parasites; flagellum; outer dynein arm docking complex; LdDC2; promastigote
Affiliations: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany. 

Abstract:  Background: In order to proceed through their life cycle, Leishmania parasites switch between sandflies and mammals. The flagellated promastigote cells transmitted by the insect vector are phagocytized by macrophages within the mammalian host and convert into the amastigote stage, which possesses a rudimentary flagellum only. During an earlier proteomic study of the stage differentiation of the parasite we identified a component of the outer dynein arm docking complex, a structure of the flagellar axoneme. The 70 kDa subunit of the outer dynein arm docking complex consists of three subunits altogether and is essential for the assembly of the outer dynein arm onto the doublet microtubule of the flagella. According to the nomenclature of the well-studied Chlamydomonas reinhardtii complex we named the Leishmania protein LdDC2. Methodology/principal findings: This study features a characterization of the protein over the life cycle of the parasite. It is synthesized exclusively in the promastigote stage and localizes to the flagellum. Gene replacement mutants of lddc2 show reduced growth rates and diminished flagellar length. Additionally, the normally spindle-shaped promastigote parasites reveal a more spherical cell shape giving them an amastigote-like appearance. The mutants lose their motility and wiggle in place. Ultrastructural analyses reveal that the outer dynein arm is missing. Furthermore, expression of the amastigote-specific A2 gene family was detected in the deletion mutants in the absence of a stage conversion stimulus. In vitro infectivity is slightly increased in the mutant cell line compared to wild-type Leishmania donovani parasites. Conclusions/significance: Our results indicate that the correct assembly of the flagellum has a great influence on the investigated characteristics of Leishmania parasites. The lack of a single flagellar protein causes an aberrant morphology, impaired growth and altered infectiousness of the parasite. 

Retracted: No

PubPeer comments:
 Retracted [8 March 2022] . ----------------------------- At the request of the authors, the Editor and Publisher of International Journal of Nanomedicine wish to retract the published article. Concerns were raised regarding the alleged duplication of images in Figure 2 and Figure 9 with similar images in Figure 4 and Figure 9 from an article published by the same authors in the International Journal of Biological Macromolecules, Asghar et al, 2020 . Specifically, - Figure 2C, panel AgNPs appears to have been duplicated with Figure 4A, panel AgNPs from Asghar et al, 2020. - Figure 2D, panel CMC-AgNPs appears to have been duplicated with Figure 4B, panel CS-AgNPs, which has been flipped, from Asghar et al, 2020. - Figure 9B, panel Streptococcus mutans appears to have been duplicated with Figure 7B, methicillin resistant Staphylococcus aureus from Asghar et al, 2020. - Figure 9C, panel Staphylococcus epidermidis appears to have been duplicated with Figure 7A, vancomycin resistant Staphylococcus aureus from Asghar et al, 2020. The authors explained the TEM images in question were provided by the first author, Muhammad Arif Asghar, and on subsequent review and investigation from this author, have confirmed these images were not satisfactory. However, all the authors accept joint responsibility for the integrity of the reported research and agree with the decision to retract the article. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as u201cRetractedu201d. ,