Caractérisation des séquences d'insertions ISCR bactériennes impliquées dans la résistance aux antibiotiques

Abstract : ISCR are a bacterial insertion sequences, recently described in clinical settings, frequently related to antibiotic resistance. These ISCR-encoded transposases belong to the well-known HUH transposases family, which transpose by rolling-circle replication. However, the transposition mechanism of ISCR transposases has not been shown experimentally. ISCR family includes 19 members and has not been well characterized yet. Therefore, we updated in silico already known characteristics for each ISCR element. Then, we investigated the involvement of ISCR1 in the expression of the downstream genes. Indeed, ISCR1 carries two outward-oriented promoters called POUT. By analyzing the diversity of the downstream region, we found that most of genes were in the same orientation as POUT promoters, suggesting these downstream genes are expressed from POUT. It thus showed that these two promoters are able to express two antibiotic resistance genes (dfrA19 and blaCTX-M-9 ). Moreover, the region containing POUT is essential to provide an ESBL-resistance phenotype for blaCTX-M-9 gene. Moreover, we also wanted to analyze the regulatory network involved in the expression of the ISCR1 transposase, RCR1. We experimentally determined that two regulatory proteins LexA and OmpR, involved in response to different stress (DNA damages and osmotic shock), control the activity of rcr1 promoter. LexA protein represses Prcr1 whereas OmpR activates Prcr1 in hypo-osmotic conditions. Here, we propose a model in which ISCR1 transposition would be the control of environmental stresses and at the same time, insured the expression of downstream antibiotic resistance genes.
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Claire Lallement. Caractérisation des séquences d'insertions ISCR bactériennes impliquées dans la résistance aux antibiotiques. Médecine humaine et pathologie. Université de Limoges, 2018. Français. ⟨NNT : 2018LIMO0035⟩. ⟨tel-02306486⟩

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