Biology subjects

Lavenir, R.

Publications and source records attributed to Lavenir, R..

4 recordsLinked to original sources

bioRxiv2025

Environment and physiology shape antiphage system expression

Bacteria and archaea encode on average ten antiphage systems. Quorum sensing, cellular, or transcription factors can regulate specific systems (CRISPR-Cas, CBASS). Yet, a systematic assessment of antiphage systems expression patterns is lacking. Here, we combine publicly available RNA-seq data from 14 different species with an original RNA-seq dataset of 15 Escherichia coli strains across six environmental conditions and two growth stages. Using this data, we explore the transcription patterns of 236 antiphage systems from 81 types. Defense system expression is variable along environmental, physiological, as well as spatial gradients, and can correlate with cellular physiology and mobile genetic element activity. We identify antiphage systems as cohesive but complex transcriptional units, find coordinated expression of defense islands possibly underpinned by local regulators, and demonstrate the functional relevance of differential expression in native systems. Together, these results suggest that environmental and physiological factors regulate prokaryotic immunity and may prime bacteria for infection.

microbiology↗

bioRxiv2025

Structural basis for Lamassu-based antiviral immunity and its evolution from DNA repair machinery

Bacterial immune systems exhibit remarkable diversity and modularity, as a consequence of the continuous selective pressures imposed by phage predation. Despite recent mechanistic advances, the evolutionary origins of many antiphage immune systems remain elusive, especially for those that encode homologs of the Structural Maintenance of Chromosomes (SMC) superfamily, which are essential for chromosome maintenance and DNA repair across domains of life. Here, we elucidate the structural basis and evolutionary emergence of Lamassu, a bacterial immune system family featuring diverse effectors but a core conserved SMC-like sensor. Using cryo-EM, we determined structures of the Vibrio cholerae Lamassu complex in both apo- and dsDNA-bound states, revealing unexpected stoichiometry and topological architectures. We further demonstrate how Lamassu specifically senses dsDNA in vitro and phage replication origins in vivo, thereby triggering the formation of LmuA tetramers that activate the Cap4 nuclease domain. Our findings reveal that Lamassu evolved via exaptation of the bacterial Rad50-Mre11 DNA repair system to form a compact, modular sensor for viral replication, exemplifying how cellular machinery can be co-opted for novel immune functions.

microbiology↗

bioRxiv2025

Protein and genomic language models chart a vast landscape of antiphage defenses

The bacterial pangenome encodes an immense array of antiphage systems, yet much of their diversity remains uncharted. In this study, we developed language models to predict novel antiphage proteins in two ways: first via fine-tuning ESM2, a protein language model capable of detecting distant homology to known defense proteins, second via a genomic language model with ALBERT architecture which predicts defensive function based on genomic context. We demonstrate that applying these approaches to Actinomycetota - a phylum largely unexplored for antiphage defenses, can accurately predict previously unknown functional defense mechanisms, leading to the discovery and experimental validation of six defense systems with novel antiphage proteins. Analysis of over 30,000 bacterial genomes predicted more than 45,000 uncharacterized protein families potentially involved in antiphage defense, underscoring the vast, untapped diversity of these systems.

microbiology↗

bioRxiv2021

β-glucan-induced innate immune memory distinctively affects macrophage activation in response to differential environmental cues

In vitro, exposure of human primary monocytes to the fungal {beta}-glucan enhances their pro-inflammatory responsiveness towards several pathogens. Yet, the role of environmental condition of this process remains unclear. Here we found that {beta}-glucan-induced innate immune memory counteract the anti-inflammatory status of the macrophages. In response to {beta}-glucan imprinting, M-CSF-(M2-like-) macrophages increase their pro-inflammatory responsiveness to secondary stimuli associated with decrease of the M-CSF differentiation hallmarks. In contrast, in GM-CSF-(M1-like-) environment, {beta}-glucan imprinting reduced the pro-inflammatory canonical feature of the macrophages, together with their terminal differentiation marks. Comparing M-CSF and GM-CSF environment, we observed that {beta}-glucan-imprinted macrophages present comparable functions in terms of cytokine responses, phagocytosis, oxidative burst, and angiogenesis. This effect is mediated through Dectin-1 and associated with altered expression of the master regulators of macrophage terminal differentiation, IRF5 and IRF3. {beta}-glucan-induced innate immune memory skews the commitment of the macrophages in complex environment towards similar and less terminally differentiated cells. Together, these observations suggest a potential therapeutic role for {beta}-glucan-induced modulation of innate memory in different pathological contexts.

immunology↗