Biology subjects

Mialhe, X.

Publications and source records attributed to Mialhe, X..

3 recordsLinked to original sources

bioRxiv2023

Circulating MicroRNAs indicative of sex and stress in the European seabass (Dicentrarchus labrax): toward the identification of new biomarkers.

MicroRNAs (miRNAs) constitute a new category of biomarkers. Studies on miRNAs in non-mammalian species have drastically increased in the last few years. Here, we explored the use of miRNAs as potential, poorly-invasive markers, to identify sex and characterize acute stress in fish. The European seabass (Dicentrarchus labrax) was chosen as model because of its rapid response to stress and its specific sex determination system, devoid of sexual chromosomes. We performed a small RNA-sequencing analysis in the blood plasma of males and females European seabass (mature and immature) as well as in the blood plasma of juveniles submitted to an acute stress and sampled throughout the recovery period (at 0h, 0.5h, 1.5h and 6h). In immature individuals, both miR-1388-3p and miR-7132a-5p were up-regulated in females, while miR-499a-5p was more abundant in males. However, no miRNAs were found to be differentially expressed between sexes in the blood plasma of mature individuals. For the acute stress analysis, five miRNAs (miR-155-5p, miR-200a-3p, miR-205-1-5p, miR-143-3p and miR-223-3p) followed cortisol production over time. All miRNAs identified were tested and validated by RT-qPCR on sequenced samples. A complementary analysis on the 3UTR sequences of the European seabass allowed to predict potential mRNA targets, some of them being particularly relevant regarding stress regulation, e.g. the glucocorticoid and the mineralocorticoid receptor. The present study provides new avenues and recommendations on the use of miRNAs as biomarkers of sex or stress of the European seabass, with potential application on other fish species.

physiology↗

bioRxiv2023

Dynamics of macrophage polarization support Salmonella persistence in a whole living organism

Numerous intracellular bacterial pathogens interfere with macrophage function, including macrophage polarization, to establish a niche and persist. However, the spatiotemporal dynamics of macrophage polarization during infection within host remain to be investigated. Here, we implement a model of persistent Salmonella Typhimurium infection in zebrafish, which allows visualization of polarized macrophages and bacteria in real time at high-resolution. While macrophages polarize toward M1-like phenotype to control early infection, during later stages, Salmonella persists inside non-inflammatory clustered macrophages. Transcriptomic profiling of macrophages confirmed a highly dynamic signature during infection characterized by a switch from pro-inflammatory to anti-inflammatory/pro-regenerative status and revealed a shift in adhesion program. In agreement with this specific adhesion signature, macrophage trajectory tracking identifies motionless macrophages as a permissive niche for persistent Salmonella. Our results demonstrate that zebrafish model provides a unique platform to explore, in a whole organism, the versatile nature of macrophage functional programs during bacterial acute and persistent infections.

immunology↗

bioRxiv2022

The aminoglycoside streptomycin triggers ferroptosis in tumor initiating cells

Compelling evidence suggests that tumor initiating cells (TIC) are the roots of current shortcomings in advanced and metastatic cancer treatment. TIC represents a minor subpopulation of tumor cells endowed with self-renewal and multi-lineage differentiation capacity, which can disseminate and seed metastasis in distant organ. Our work identified Streptomycin (SM), a potent bactericidal antibiotic, as a new molecule capable of targeting non-adherent TIC from colon and breast cancer cell lines by inducing mitochondrial-dependent ferroptosis. SM-induced ferroptosis associates with profound alterations in mitochondrial morphology, such as swelling and cristae enlargement, coupled with hyperpolarization of mitochondrial membrane potential and production of mitochondrial ROS. The peculiar SM structure, and more particularly its aldehyde group, is essential for this mechanism. As such, the mere reduction of SM into dihydrostreptomycin abolishes its effect on TIC. This study reveals a new mechanism of action of SM that could help comprehend the molecular basis of TIC adaptation to inhospitable environments and pave the way for new treatment of advanced cancers.

cancer biology↗