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Biology subjects

Bergman, P.

Publications and source records attributed to Bergman, P..

3 recordsLinked to original sources

A novel mechanism for centrosome expulsion ensures metabolic activity in polyploid cells

Programmed polyploidy is often linked to increase cell size to support enhanced metabolism, barrier function or regeneration. In certain polyploid cells, the cytoskeleton is drastically remodeled-most notably by eliminating centrosomes. However, the purpose and mechanisms underlying centrosome elimination have remained unclear. We investigated this question in Drosophila acentrosomal salivary glands (SGs), a physiological polyploid model where cells reach high chromosome content through endoreplication. Using genetic tools, live imaging approaches, super-resolution microscopy combined with tissue clearing and electron microscopy, our study uncovers a novel centrosome elimination pathway in vivo. This process requires non-muscle myosin II (MyoII) activity and the macroautophagic machinery to drive centrosome release into the lumen of the salivary glands via autolysosomal exocytosis. Failure to eliminate centrosomes disrupts the mitochondria network, impairing respiration and ATP production. Our findings reveal a previously unknown mechanism that removes centrosomes through the secretory autophagy pathway to protect mitochondrial function and support the high metabolic demands of polyploid cells.

cell biology↗

Effects of stress coping styles and social defeat on zebrafish behaviour and brain transcriptomics

Individuals with divergent personality traits corresponding to stress coping styles have been suggested to differ in behavioural and neural plasticity. To assess the effects of social experience on the coping ability of wild zebrafish selectively bred for boldness/shyness, we used a model of social defeat stress. Behavioural tests were performed to assess parameters such as boldness/exploration, aggressiveness, and displaced behaviour. Gene expression changes in the brain were assessed via RNA sequencing. The main results suggest a strong effect of shyness and boldness phenotype on behaviour and brain transcriptome. Fish of the shy line displayed significant behavioural changes, while the number of differentially expressed genes remained low. In contrast, fish of the bold line exhibited a small effect on behaviour and pronounced changes in brain gene expression. This study highlights the importance of boldness phenotype and its influence on the response to social challenges at the behavioural and transcriptomic levels.

animal behavior and cognition↗

Human MAIT cell cytolytic effector proteins synergize to overcome carbapenem resistance in Escherichia coli

Mucosa-associated invariant T (MAIT) cells are abundant antimicrobial T cells in humans, and recognize antigens derived from the microbial riboflavin biosynthetic pathway presented by the MHC-Ib-related protein (MR1). However, the mechanisms responsible for MAIT cell antimicrobial activity are not fully understood, and the efficacy of these mechanisms against antibiotic resistant bacteria has not been explored. Here, we show that MAIT cells mediate MR1-restricted antimicrobial activity against E. coli clinical strains in a manner dependent on the activity of cytolytic proteins, but independent of production of pro-inflammatory cytokines or induction of apoptosis in infected cells. The combined action of the pore-forming antimicrobial protein granulysin and the serine protease granzyme B released in response to TCR-mediated recognition of MR1-presented antigen is essential to mediate control against both cell-associated and free-living E. coli. Furthermore, MAIT cell-mediated bacterial control extend to multidrug-resistant E. coli primary clinical isolates additionally resistant to carbapenems, a class of last resort antibiotics. Notably, high levels of granulysin and granzyme B in the MAIT cell secretomes directly damage bacterial cells by increasing their permeability, rendering initially resistant E. coli susceptible to the bactericidal activity of carbapenems. These findings define the role of cytolytic effector proteins in MAIT cell-mediated antimicrobial activity, and indicate that granulysin and granzyme B synergize to restore carbapenem bactericidal activity and overcome carbapenem resistance in E. coli. One Sentence SummaryPotent antimicrobial activity of human MAIT cells overcomes carbapenem-resistance in control of Escherichia coli

immunology↗