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Stress endogènes et acquisition de résistance aux antibiotiques par les intégrons en biofilm

Abstract : In natural settings, bacteria mostly live in biofilms. These are highly tolerant to antibiotics and cause persistent infections that are difficult to treat. Class 1 integrons are bacterial systems able to capture, exchange and express antibiotic resistance gene. The integrase IntI1, whose expression is regulated by the bacterial SOS response, catalyzes the insertion/excision of gene cassettes. We have previously shown that the basal expression level of intI1 and sfiA (SOS regulon gene) is globally increased via the stringent response (induced during nutrient starvation) in biofilm compared to planktonic culture. However, biofilms are heterogeneous environments where bacteria exhibit various phenotypes.In this study, we localized and quantified the expression of intI1 and sfiA genes within the biofilm at the level of individual bacteria, using confocal microscopy, flow cytometry and RTqPCR approaches. Our results showed that in absence of exogenous stress, only a small number of bacteria (~ 1%) located in the depth of the biofilm induce the SOS response leading to a high level of intI1 and sfiA expression, both in a stringent response-dependent and -independent manner. Our results thus indicate that few bacteria located at the depth of the biofilm undergo sufficient endogenous stress to promote the acquisition of antibiotic resistance, forming a reservoir of bacteria ready to rapidly resist antibiotic treatments.We also showed the involvement of the global regulator CRP in biofilm-specific regulation of integrase expression, a more complex regulation than expected.
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https://tel.archives-ouvertes.fr/tel-03738134
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Submitted on : Monday, July 25, 2022 - 5:25:56 PM
Last modification on : Thursday, October 13, 2022 - 3:22:50 PM
Long-term archiving on: : Wednesday, October 26, 2022 - 7:26:33 PM

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  • HAL Id : tel-03738134, version 1

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Linda Tlili. Stress endogènes et acquisition de résistance aux antibiotiques par les intégrons en biofilm. Médecine humaine et pathologie. Université de Limoges, 2021. Français. ⟨NNT : 2021LIMO0067⟩. ⟨tel-03738134⟩

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