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Froissart, R.

Publications and source records attributed to Froissart, R..

6 recordsLinked to original sources

Sialidase variability in Gardnerella: genetics, taxonomy, function, and clinical presentation

Bacterial vaginosis (BV) is the most common vaginal condition among women of reproductive age. Despite over six decades of research, the pathogenesis and etiology of BV remain largely unknown. Members of the Gardnerella genus are common components of the healthy vaginal microbiota, although their uncontrolled proliferation plays a key role in BV pathogenesis. Recent taxonomic revisions have highlighted extensive genetic and functional diversity among Gardnerella spp., but the relationship between genetics, taxonomy, and virulence remains elusive. Sialidases are key virulence factors in BV, degrading the protective epithelial mucus layer, facilitating colonization and releasing carbon and nitrogen sources. However, robust clinical evidence linking sialidases to increased BV risk remains limited. Here, we analyzed clinical Gardnerella isolates from BV-positive (75%) and BV-negative (25%) samples (n = 66) collected at the University Hospital of Montpellier, France. We inferred phylogenetic relationships, characterised the nanH sialidase gene repertoire, quantified in vitro sialidase activity, and evaluated antibiotic resistance profiles. Most isolates belonged to Gardnerella clades 1, 2, and 4 (63.6%, 19.7%, and 16.7%, respectively). The three nanH genes were unevenly distributed across clades: nanH1 was most common ([~]80%), highly prevalent in clades 1-3; nanH2 was rare (6%); and nanH3 ([~]38%) was predominantly found in clade 2 - typically co-occurring with nanH1. Sialidase activity varied both between and within clades, and was only weakly associated with the nanH gene repertoire. Neither taxonomy nor sialidase-associated traits were reliable predictors of BV status, and we found no clear link between taxonomy and antibiotic resistance. Together, these results reveal substantial discordance in the genotype-phenotype relationship in Gardnerella, suggesting epigenetic, physiological and/or ecological modulation. Our findings highlight the need for a better understanding of bacterial physiology, plasticity, and ecology to explain microbial traits of clinical importance.

microbiology↗

Environmental complexity constrains evolutionary adaptation across taxa

Complex environments combining multiple stressors are the new norm worldwide. Adaptive evolution will be critical to population persistence under these combined challenges, but how environmental complexity affects the pace of evolution remains poorly understood. Using a meta-experimental evolution approach, we exposed 14 species, from bacteria to unicellular eukaryotes and plants, to single stressors and their pairwise combinations for multiple generations, while keeping the overall stress level comparable. Populations evolving under combined stressors tended to have lower fitness increase in the selective environments, higher fitness reductions in the control environment, and shallower relation between initial maladaptation and fitness gain, than under single stressors. However, these responses varied with species and stressor type. Accounting for such constraints on evolutionary dynamics should prove crucial for the management of biodiversity. Significance StatementA pressing challenges for modern science and society in the face of ongoing global change is understanding what limits the capacity of living organisms to adapt to complex environments combining multiple stressors. To answer to this question, we conducted a large-scale meta-experimental evolution design across a diversity of organisms, exposing them for multiple generations to either single or combined-stress treatments. Combined stressors led to less adaptive fitness gain than single stressors, and imposed additional costs through reduced fitness in non-stressful conditions. This unique combination of meta-experimental approach with a careful distinction between environmental complexity and overall stress allowed us to gain robust quantitative evidence on how environmental complexity can impact the pace of evolution.

evolutionary biology↗

The complete genome and comparative analysis of a new Tequintavirus: Salmonella phage Tennessee Salten

The rise in multidrug-resistant pathogenic bacteria presents a major current challenge, highlighting the urgent need for alternatives and sustainable biocontrol strategies. Here, we report the genome analysis of a bacteriophage called Salmonella phage Tennessee Salten and attributed to a new Tequintavirus species. Salten was isolated following infection of Salmonella enterica subsp. enterica serotype Tennessee (sequence type ST5018). Its genome is 109,999 bp in length and contains 220 predicted proteins on which 197 are CDS and 23 tRNAs. Compared to its closest known relative phage Escherichia phage HildyBeyeler - sharing 84.6% identity - Salten harbours 16 unique or highly divergent genes. Of these, 13 encode proteins with unknown function, one encodes for a putative adenine methyltransferase and two encode HNH homing endonucleases. Moreover, the Long Tail Fibre protein, whose structure was predicted based on that of phage T5, was highly divergent among the Tequintavirus genus.

microbiology↗

"This training is bound for glory": selection by experimental evolution of a bacteriophage with expanded host-range and increased virulence

Viral host range expansion is predicted to evolve at the cost of reduced mean fitness. We investigated the adaptive walks of a virulent phage (Tequintavirus) in a spatially variable environment composed of four susceptible bacterial isolates and four resistant ones (Salmonella enterica serotype Tennessee, sequence types ST5018 and ST319 respectively). Starting from a single ancestral phage, we evolved multiple independent populations through serial passages on non-coevolving bacteria, following the Appelmans protocol. The phage populations evolved an expanded host range and increased virulence. Whole-genome sequencing revealed recurrent parallel mutations across populations (i.e. convergent evolution), particularly in genes encoding exo- and endo-nucleases, dUTPase, and caudal proteins. Notably, two parallel mutations in the gene coding for the Long Tail Fibre became fixed early in the evolutionary trajectories. Reverse-genetics experiments introducing these mutations into the ancestral genome expanded the host range but yielded only marginal increases in virulence, highlighting the effect of compensatory mutations. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=115 SRC="FIGDIR/small/584857v3_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@cec6b5org.highwire.dtl.DTLVardef@1579ba4org.highwire.dtl.DTLVardef@ab5ad5org.highwire.dtl.DTLVardef@1d88160_HPS_FORMAT_FIGEXP M_FIG C_FIG Highlights* A phage (Tequintavirus) was evolved on susceptible and resistant Salmonella enterica strains * Experimentally evolved phage populations displayed expanded host range and increased virulence * Convergent evolution revealed adaptive mutations modifying receptor recognition in caudal proteins * Reverse-genetic showed implication of two Long Tail Fibre mutations in host range expansion In BriefGeneralism is traditionally predicted to evolve at the cost of lower mean fitness. Contrary to this textbook view, we demonstrate that generalist phages with expanded host range and increased virulence can readily evolve in vitro and be purposely optimized for phage therapy applications.

evolutionary biology↗

Gene editing is suitable to treat GM1 Gangliosidosis: a proof-of-concept study

Ganglioside-monosialic acid (GM1) gangliosidosis, a rare autosomal recessive disorder, is frequently caused by deleterious single nucleotide variants (SNVs) in GLB1 gene. These variants result in reduced {beta}-galactosidase ({beta}-gal) activity, leading to neurodegeneration associated with premature death. Currently, no effective therapy for GM1 gangliosidosis is available. Three ongoing clinical trials aim to deliver a functional copy of the GLB1 gene to stop disease progression. Here, we show that 41% of GLB1 pathogenic SNVs might be cured by adenine base editors (ABEs). Our results demonstrate that ABE efficiently corrects the pathogenic allele in patient-derived fibroblasts, restoring a therapeutic level of {beta}-gal activity. Unbiased off-target DNA analysis did not detect off-target editing activity in treated patients cells except a bystander edit without consequences on {beta}-gal activity. Altogether our results suggest that gene editing is an alternative strategy to cure GM1 gangliosidosis, by correcting the root cause of disease and avoiding repetitive adeno-associated virus injections.

genetics↗

Maintenance of Polymorphism in Spatially Heterogeneous Environments: An Experimental Test of Hard and Soft Selection

This preprint has been reviewed and recommended by Peer Community In Evolutionary Biology (http://dx.doi.org/10.24072/pci.evolbiol.100020). Predicting and managing contemporary adaption requires a proper understanding of the determinants of genetic variation. Spatial heterogeneity of the environment may stably maintain polymorphism when habitat contribution to the next generation can be considered independent of the degree of adaptation of local populations within habitats (i.e., under soft selection). In contrast, when habitats contribute proportionally to the mean fitness of the populations they host (hard selection), polymorphism is not expected to be maintained by selection. Although mathematically established decades ago, this prediction had never been properly explored. Here we provide an experimental test in which polymorphic populations of Escherichia coli growing in heterogeneous habitats were exposed to hard and soft selection regimes. As predicted by theory, polymorphism was longer preserved under soft selection. Complementary tests established that soft selection slowed down fixation processes and could even protect polymorphism on the long term by providing a systematic advantage to rare genotypes.

evolutionary biology↗