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Deciphering in vivo efficacy of virulent phages in the mammalian gut

Abstract : The mammalian gut is a heterogeneous environment inhabited by a large and diverse microbial community, including bacteria and their viral predators, bacteriophages (phages). Dynamic interactions between virulent phages and bacteria in the gut are still poorly understood, which is also an obstacle for the design of successful therapeutic interventions based on phages. Independent experiments have shown that virulent phages were found to have no major effects on their targeted bacteria in the gut, in spite of sustainable phage amplification. This suggests that there are unknown factors in the gut environment that modulate these interactions. Using comparative transcriptomics analysis of E. coli grown in vitro and in vivo (within the mammalian gut) we found that in the gut, bacteria downregulate the expression of genes related to phage receptors, which provides an explanation for the lack of selection of phage-resistant bacteria during in vivo experiments. We also found that the acquisition of a pathogenicity island commonly found in human E. coli isolates affects phage susceptibility possibility by downregulating a defense mechanism against invading DNA. Finally, we examined the repartition of phages and bacteria through mucosal and luminal gut sections and observed a heterogeneous spatial distribution of these two antagonist populations, supporting the hypothesis of source-sink dynamics. Altogether our data demonstrates that multiple factors encompassing, spatial distribution, bacterial physiology and defenses against foreign DNA modulate the interactions between bacteria and phages within the gut.
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Submitted on : Wednesday, April 28, 2021 - 1:01:58 AM
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MANSOS_LOURENCO_Marta_2019.pdf
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  • HAL Id : tel-03210493, version 1

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Marta Mansos Lourenço. Deciphering in vivo efficacy of virulent phages in the mammalian gut. Bacteriology. Sorbonne Université, 2019. English. ⟨NNT : 2019SORUS260⟩. ⟨tel-03210493⟩

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