ArticleBMC microbiology2025
Identification of Cdc45-interacting partners uncovers two Leishmania donovani proteins involved in DNA replication.
Article in BMC microbiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
Abstract
backgroundAmong fatalities due to parasitic diseases, deaths due to Leishmaniases rank second only to those caused by malaria. Endemic to 90 countries, more than a billion people are at risk of Leishmania infection. While there are no vaccines against Leishmaniases, treatments are available. However, the complexities of the treatment regimens, their high costs and toxic side effects, and most importantly the emerging problem of drug resistance, have continued to thrust forward research into this parasite's cellular processes. The parasite is digenetic, reproducing by binary fission in both hosts, with DNA replication being central to the process. The absence of many conserved DNA replication proteins in Leishmania suggests the possibility of parasite-specific proteins being involved in the process. This investigation aimed to identify such proteins.
methodsUsing Leishmania donovani Cdc45, a component of the eukaryotic replicative helicase, as bait in immunoprecipitation reactions coupled to mass spectrometry, we looked for proteins that are a part of the Leishmania replisome. One of the promising candidates, annotated "hypothetical protein" in the Leishmania genome database, shared partial structural homology with Timeless of human, C. elegans and Drosophila, and hence we named it "LdTIM-like". A second candidate, annotated "PIF1-like" in the genome database, was named "LdPIF6" based on sequence homology with T.brucei PIF6. Their possible involvement in DNA replication was examined by creating genomic knockouts and analyzing resultant phenotypes.
resultsLdTIM-like and LdPIF6 were constitutively nuclear, in keeping with a possible role in DNA replication. We found tim-like and pif6 were essential for parasite survival. Single allele knockouts lowered tim-like/pif6 expression significantly, and resulted in slower parasite growth. The mutant parasites took considerably longer to navigate S phase, and pulse-labelling with EdU revealed that the time taken by the mutant cell populations to complete DNA replication was significantly extended. The mutant parasites survived poorly in host macrophages as well.
conclusionsConsidering that these two proteins: LdTIM-like and LdPIF6, are essential to the parasite, coupled to their limited homology with human proteins, they could be investigated as potential sites for therapeutic intervention in future in-depth studies.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.