Kaufman, Y. | Search bioRxiv

bioRxiv2021

An SR protein is essential for the recovery of malaria parasites from DNA damage and exposure to artemisinin

Plasmodium falciparum, the parasite responsible for the deadliest form of human malaria, maintains a complex life cycle with a relatively small number of genes. PfSR1 is an alternative splicing factor that regulates expansion of the P. falciparum protein repertoire. To further investigate PfSR1 functions, we set to unveil its interactome. We found that PfSR1 interacts with proteins, which are linked to various processes of RNA metabolism in a stage-dependent manner. These include: chromatin re-modeling, transcription, splicing and translation. Intriguingly, some of the PfSR1 interacting proteins are orthologues of proteins implicated in the DNA damage response. We demonstrate that PfSR1 expression is important for preventing the accumulation of DNA damage in proliferating parasites. In addition, following parasites exposure to a source of DNA damage, PfSR1 is recruited to damaged foci where it interacts with the phosphorylated core histone PfH2A, which marks damaged chromatin. Furthermore, PfSR1 expression was found to be essential for the ability of the parasite to activate the DNA repair machinery and recover from DNA damage caused by either irradiation or exposure to artemisinin, the first line anti-malarial drug. These findings unveil a novel role of PfSR1 in protecting P. falciparum from DNA damage and artemisinin exposure.

microbiology↗

bioRxiv2020

Bursting out: linking changes in nano-topography and biomechanical properties of biofilm-forming Escherichia coli to T4 lytic cycle

Bacteriophage infection cycle has been extensively studied, yet little is known on the structural and mechanical changes that lead to bacterial lysis. Here, bio-atomic force microscopy was used to study in real-time and in-situ the impact of the canonical phage T4 on the nano-topography and biomechanics of irreversibly attached, biofilm-forming E. coli cells. The results show that in contrast to the lytic cycle in planktonic cells, which ends explosively, anchored cells that are in the process of forming biofilms undergo gradual lysis, developing distinct sub-micron lesions ([~]300 nm in diameter) within the cell envelope. Furthermore, it is shown that the envelope rigidity and cell elasticity decrease (>50% and >40%, respectively) following T4 infection. These new insights show that the well-established lytic pathway of planktonic cells may be significantly different from that of biofilm-forming cells. Elucidating the lysis paradigm of these cells may advance biofilm removal and phage therapeutic. There is no conflict of interest and all co-authors have seen and approved the current version for submission.

microbiology↗