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BENAROUDJ, N.

Publications and source records attributed to BENAROUDJ, N..

3 recordsLinked to original sources

Linking genomic evolutionary transitions to ecological phenotypic adaptations in Spirochaetes

Understanding the genetic basis of ecological adaptation is a fundamental challenge of evolutionary biology. Spirochaetes are an ancient bacterial phylum of exceptional ecological breadth, encompassing major human pathogens such as the causative agents of syphilis, Lyme disease, and leptospirosis, alongside free-living species from contrasting environments and recently described species that lack the canonical spiral morphology of the phylum. Here, using a curated dataset of genomes representing all cultivable spirochete species, we show that functional genome architecture (defined as the proportional allocation of coding capacity across biological processes) correlates with ecological lifestyle and phenotypic traits in Spirochaetes independently of phylogenetic relationships, with host-dependent lineages from distinct evolutionary origins converging on shared functional profiles. Phylum-wide phylogenomic analyses identified Brachyspira as the earliest-diverging lineage, revisiting the evolutionary rooting of the phylum, and establishing that the spiral morphology is ancestral and was lost in a single evolutionary transition also associated with coordinated functional changes. Lastly, ancestral genome reconstruction uncovers the common ancestor as a motile, heterotrophic, and spiral-shaped bacterium, with metabolic and structural features not previously described. Together, these results provide an integrated and functional framework for Spirochaetes, illustrating how genome architecture can be used to track the ecological diversification of a widespread bacterial phylum.

microbiology↗

In Vivo Dual RNA-Seq uncovers key toxin-like effectors of epithelial barrier disruption and tissue colonization by an extracellular bacterial pathogen

Disruption of host cell barriers is a fundamental strategy enabling pathogens to establish a paracellular infection. Using dual RNA-Seq, we determined the in vivo host-pathogen transcriptomic landscape upon infection by the extracellular pathogen Leptospira interrogans and uncovered a novel mechanism of cell-cell junction disruption. We demonstrated that, upon infection, an increase in intracellular calcium triggered tight junction destabilization, by activating the calmodulin and myosin light chain kinase signalization. We identified two novel bacterial effectors of the Virulence-Modifying (VM) proteins family, structurally related to toxin-like proteins, that promoted modulation of calcium homeostasis and disruption of cell-cell junctions, thereby allowing Leptospira translocation across epithelium barriers, tissue colonization and pathogenicity. Furthermore, we demonstrated that at least one of these VM proteins was internalized inside host cells. Altogether, these findings reveal a unique strategy by which an extracellular pathogen secretes toxin-like proteins to exploit host calcium signaling for breaching epithelial barriers.

microbiology↗

Revisiting oxygen toxicity: evolution and adaptation to superoxide in a SOD-deficient bacterial pathogen

Defenses against oxidants are crucial for the virulence of pathogens, with superoxide scavenging enzymes (SOSEs) playing a vital role for most aerobes. However, our knowledge of superoxide adaptation primarily stems from the study of SOSE-encoding bacteria. Here, we investigated the evolution of a naturally SOSE-deficient pathogen (Leptospira spp.), along with the alternative mechanisms it recruits to combat superoxide stress. We demonstrate that emergence of pathogenic Leptospira correlated with SOD loss, but that a long-lasting adaptation to superoxide remains possible. We reveal that cysteine and leucine biosynthesis are the most induced pathways in response to superoxide and demonstrate the importance of sulfur metabolism in superoxide adaptation in this SOSE-deficient model. We also propose cysteine oxidation as a key mediator of superoxide toxicity in the absence of SOSEs. This study challenges our conventional understanding of the oxygen toxicity theory and proposes a new model of superoxide adaptation through metabolic rewiring in bacteria.

microbiology↗