Biology subjects

Ducos-Galand, M.

Publications and source records attributed to Ducos-Galand, M..

3 recordsLinked to original sources

bioRxiv2026

Coupling metabolic enhancement to plasmid spread enables programmable antimicrobial control

The rise of multidrug-resistant pathogens underscores the need for precise antimicrobial strategies that extend beyond conventional antibiotics. Conjugation-based approaches offer a powerful yet underexploited means of delivering targeted genetic interventions directly within microbial communities. In this work, we combined selective killing modules with rationally optimized conjugative vectors to target antibiotic-resistant pathogens and clinically relevant antimicrobial resistance plasmids. First, we engineered and validated toxin-intein modules, programmable cassettes that restrict toxic activity to highly specific regulatory contexts. Specifically, we developed and validated modules targeting Shigella spp., Salmonella enterica, and bacteria carrying the resistance plasmid pOXA-48, demonstrating a tunable system capable of selective activity at both the species and strain levels. To identify the most effective delivery platform, we compared mobilizable and conjugative systems and found that, in vitro, conjugative plasmids consistently outperformed mobilizable ones by approximately one order of magnitude. To further optimize delivery, we streamlined the broad-host-range plasmid RP4 and enhanced its functionality by incorporating either the metabolic fos locus, which confers a fitness advantage to cells carrying the delivery vehicle; a type IV pilus operon that promotes mating-pair stabilization and enables efficient conjugation in liquid environments; or both features combined. Using these engineered RP4 derivatives, we integrated the toxin-intein module targeting pOXA-48 and evaluated its performance in complex microbial communities. In this setting, the RP4 variant carrying both the fos locus and the type IV pilus operon effectively blocked the spread of pOXA-48. Together, this work advances the use of conjugative plasmids as robust and programmable platforms to combat antibiotic resistance and enable microbiome engineering. Beyond introducing highly specific antimicrobial modules and a new generation of optimized conjugative vectors, our results identify ecological competitiveness and plasmid transfer dynamics as critical determinants of the success of such interventions.

microbiology↗

bioRxiv2025

Unraveling the prevalence and multifaceted roles of accessory peptide deformylases in bacterial adaptation and resistance

Peptide deformylases (PDFs) are enzymes that are essential for bacterial viability and attractive targets for antibiotic development. Yet, despite their conserved function, many bacteria encode multiple PDFs, a genomic feature whose prevalence and implications remain largely unexplored. Here, we reveal that nearly half of all bacterial genomes carry more than one PDF gene, frequently embedded within mobile genetic elements such as plasmids and integrons. In Vibrio cholerae, the accessory PDF (Def2VCH) confers reduced susceptibility to actinonin (ACT), the most studied PDF inhibitor, while still supporting bacterial growth in absence of the canonical PDF copies (Def1VCH). Crystallographic analysis shows that this reduced susceptibility stems from an arginine-to-tyrosine substitution that probably reduces ACT binding. Strikingly, this resistance signature is shared by integron-encoded PDFs, and transfer of an integron-encoded PDF cassette from Pseudoxanthomonas into a susceptible V. cholerae is sufficient to abolish ACT susceptibility. These findings expose a cryptic reservoir of resistance within the bacterial mobilome and highlight a challenge to the therapeutic potential of PDF-targeting antibiotics: resistance may not only emerge, but is already encoded, mobile, and ready to spread.

microbiology↗

bioRxiv2024

Long-term evolution reveals the role of the circadian cycle in the environmental adaptation of cyanobacteria

Circadian clocks synchronize internal cellular states with diurnal rhythms. Widespread in bacteria and eukaryotes, they regulate a variety of physiological processes, from hormone secretion in animals to carbon fixation in photosynthetic organisms. The adaptive role of circadian clocks is assumed to stem from their ability to anticipate environmental change, yet their impact on ecological adaptation remains unclear. Here, we use experimental evolution to study the interplay between fitness and circadian regulation in the model cyanobacterium Synechococcus elongatus PCC 7942. After 1,200 generations under continuous, high-intensity illumination, we obtained a strain that grew six times faster than its ancestral counterpart. Genome sequencing revealed three mutations fixed in the population, two of which replicated the fast-growing phenotype in the wild-type. A deletion in SasA, a key circadian regulator, was essential for fast growth. Transcriptomic and metabolomic analyses revealed that this mutation perturbed the rhythmicity of the cycle, while simultaneously locking the cell in a transcriptomic response to high intensity illumination. A comparison with another fast- growing isolate, UTEX 2973, showed convergent transcriptomic states despite different driving mutations. Our results indicate that the clock acts not only as a timekeeping device, but also as an adaptive mechanism to optimize growth across diverse ecological conditions.

microbiology↗