Biology subjects

Drame, M.

Publications and source records attributed to Drame, M..

3 recordsLinked to original sources

bioRxiv2026

Sexual conflict, directional sexual selection and phenotypic plasticity jointly drive the evolution of extreme phenotypic variation

How broad phenotypic variation is maintained in natural populations in the face of selection is a central question in evolutionary biology. We address this question in the water strider Microvelia longipes, where males exhibit striking variation in rear leg length used in male-male contests for dominance. Using reaction norm experiments on inbred lines, we demonstrate that phenotypic plasticity contributes to expanding phenotypic variation, but requires high genetic variation to generate the broad range of trait expression observed in natural populations. Experimental evolution favouring trait exaggeration revealed that directional sexual selection not only fails to erode variation of male rear leg length, but rather amplifies it beyond the natural distribution. Additionally, male-limited selection in favour of dominance generated substantial fecundity costs in females, underscoring the role of sexual conflict driven by females in constraining exaggerated secondary sexual traits in males. Our findings show that sexually antagonistic selection and directional sexual selection jointly generate high genetic variation, which phenotypic plasticity inflates into broad phenotypic distribution of male weapon size. This provides an empirical explanation for the high variability of male exaggerated weapons in nature.

evolutionary biology↗

bioRxiv2024

Backtracking Metabolic Dynamics in Single Cells Predicts Bacterial Replication in Human Macrophages

Accurately tracking dynamic state transitions is crucial for modeling and predicting biological outcomes, as it captures heterogeneity of cellular responses. To build a model to predict bacterial infection in single cells, we have monitored in parallel infection progression and metabolic parameters in thousands of human primary macrophages infected with the intracellular pathogen Legionella pneumophila. By combining livecell imaging with a novel tool for classifying cells based on infection outcomes, we were able to trace the specific evolution of metabolic parameters linked to distinct outcomes, such as bacterial replication or cell death. Our findings revealed that early changes in mitochondrial membrane potential ({Delta}{psi}m) and in the production of mitochondrial Reactive Oxygen Species (mROS) are associated with macrophages that will later support bacterial growth. We used these data to train an explainable machine-learning model and achieved 83% accuracy in predicting L. pneumophila replication in single, infected cells before bacterial replication starts. Our results highlight backtracking as a valuable tool to gain new insights in host-pathogen interactions and identify early mitochondrial alterations as key predictive markers of success of bacterial infection.

microbiology↗

bioRxiv2021

Reverting the mode of action of the mitochondrial FOF1-ATPase by Legionella pneumophila preserves its replication niche

Legionella pneumophila, the causative agent of Legionnaires disease, a severe pneumonia, injects via a type-IV-secretion-system (T4SS) more than 300 proteins into macrophages, its main host cell in humans. Certain of these proteins are implicated in reprogramming the metabolism of infected cells by reducing mitochondrial oxidative phosphorylation (OXPHOS) early after infection. Here we show that despite reduced OXPHOS, the mitochondrial membrane potential ({Delta}{psi}m) is maintained during infection of primary human monocyte-derived macrophages (hMDMs). We reveal that L. pneumophila reverses the ATP-synthase activity of the mitochondrial FOF1-ATPase to ATP-hydrolase activity in a T4SS-dependent manner, which leads to a conservation of the {Delta}{psi}m, preserves mitochondrial polarization and prevents macrophage cell death. Analyses of T4SS effectors known to target mitochondrial functions revealed that LpSpl is partially involved in conserving the {Delta}{psi}m, but not LncP and MitF. The inhibition of the L. pneumophila-induced "reverse mode" of the FOF1-ATPase collapsed the {Delta}{psi}m and caused cell death in infected cells. Single-cell analyses suggested that bacterial replication occurs preferentially in hMDMs that conserved the {Delta}{psi}m and showed delayed cell death. This direct manipulation of the mode of activity of the FOF1-ATPase is a newly identified feature of L. pneumophila allowing to delay host cell death and thereby to preserve the bacterial replication niche during infection.

microbiology↗