Biology subjects

Garneau, J.

Publications and source records attributed to Garneau, J..

3 recordsLinked to original sources

bioRxiv2024

A phylogenetic host range index reveals contrasted relationships between phage virulence and specialisation

Phages are typically known for having a limited host range, targeting various strains within a specific bacterial species. However, factors like the phylogeny or epidemiology of host bacteria are often disregarded, despite their potential influence on phage specialization and virulence. This research utilizes a new "phylogenetic host range index" that accounts for the genetic diversity of bacterial hosts, to classify phages into specialists and generalists accurately. We provide evidence that the CRISPR-Cas immune system of bacteria more frequently targets generalist phages than specialist phages. We explore the hypothesis that generalist phages might exhibit lower virulence than specialist ones due to potential evolutionary trade-offs between host range breadth and virulence. Importantly, contrasted correlations between phage virulence and host range depend on the epidemiological context. A trade-off was confirmed in a homogeneous bacterial epidemiology situation, but not in more complex epidemiological scenario, where no apparent costs were detected for phages adapted to a wide range of hosts. This study highlights the need for genetic analyses in phage host range and of investigating ecological trade-offs that could improve their applications in biocontrol or therapy.

microbiology↗

bioRxiv2024

Exposure of gut bacterial isolates to the anthelminthic drugs, ivermectin and moxidectin, leads to antibiotic-like phenotypes of growth inhibition and adaptation.

Due to their broad-spectrum activities, ivermectin and moxidectin are widely used anthelminthics in veterinary and human medicine. However, ivermectin has recently been shown to perturbate gut-microbial growth. Given the macrolide-like structure of both ivermectin and moxidectin, there is a need to characterize the antibiotic spectrum of these anthelminthic drugs and their potential implications in the development of cross-resistance to macrolides and other families of antibiotics. Here, we incubated 59 bacterial isolates representing different clades frequently found in the gut with ivermectin and moxidectin at different concentrations for 16-72h. Further, we challenged 10 bacterial isolates with repeated and gradually increasing concentrations of these two anthelminthics and subsequently characterized their sensitivity to different antibiotics as well as ascending anthelminthic concentrations. We found, that antibacterial activity of the two anthelminthics is comparable to a selection of tested antibiotics, as observed by potency and dose dependence. Bacterial anthelminthic challenging in vitro resulted in decreased anthelminthic sensitivity. Further, adaptation to anthelminthics is associated with decreased antibiotic sensitivity towards three macrolides, a lincosamide, a fluoroquinolone, a tetracycline and two carbapenems. The observed change in bacterial sensitivity profiles is associated with - and likely caused by - repeated anthelminthic exposure. Hence, current and future large-scale administration of ivermectin and moxidectin, respectively, for the control of helminths and malaria raises serious concerns - and hence potential off-target effects should be carefully monitored.

microbiology↗

bioRxiv2022

Chromosome folding and prophage activation reveal gut-specific genome dynamics of bacteria in the OMM12 consortium

Bacteria and their viruses, bacteriophages, are the most abundant entities of the gut microbiota, a complex community of microorganisms associated with human health and disease. In this ecosystem the interactions between these two key components are still largely unknown. In particular, the impact of the gut environment on bacteria and their associated prophages is yet to be deciphered. To gain insight into the activity of lysogenic phages within the context of their host genomes, we performed Hi-C on the 12 strains of the OMM12 synthetic bacterial community stably associated within mice gut (gnotobiotic mouse line OMM12) in both in vitro and in vivo conditions. High-resolution contact maps of the chromosome 3D organization of the bacterial genomes revealed a wide diversity of architectures, differences between environments and an overall stability over time in the gut of mice. The DNA contacts also pointed at 3D signatures of prophages leading to predict 16 of them as functional. We identified circularization signals and observed different 3D patterns depending on the condition. Concurrent virome analysis showed that 11 of these prophages produced viral particles in vivo and/or in vitro, and that OMM12 mice do not carry other intestinal viruses. By predicting functional prophages, the Hi-C approach unlocks the study of phage-bacteria interaction dynamics.

microbiology↗