Evidence for induction of integron-based antibiotic resistance by the SOS response in a clinical setting.Reportar como inadecuado

Evidence for induction of integron-based antibiotic resistance by the SOS response in a clinical setting. - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

* Corresponding author 1 API - Agents pathogènes et inflammation - UFC EA 4266 2 Department of Immunology, Medicine and Microbiology 3 LCE - Laboratoire Chrono-environnement 4 Hôpital Jean Minjoz 5 PGB - Plasticité du Génome Bactérien

Abstract : Bacterial resistance to β-lactams may rely on acquired β-lactamases encoded by class 1 integron-borne genes. Rearrangement of integron cassette arrays is mediated by the integrase IntI1. It has been previously established that integrase expression can be activated by the SOS response in vitro, leading to speculation that this is an important clinical mechanism of acquiring resistance. Here we report the first in vivo evidence of the impact of SOS response activated by the antibiotic treatment given to a patient and its output in terms of resistance development. We identified a new mechanism of modulation of antibiotic resistance in integrons, based on the insertion of a genetic element, the gcuF1 cassette, upstream of the integron-borne cassette blaOXA-28 encoding an extended spectrum β-lactamase. This insertion creates the fused protein GCUF1-OXA-28 and modulates the transcription, the translation, and the secretion of the β-lactamase in a Pseudomonas aeruginosa isolate S-Pae susceptible to the third generation cephalosporin ceftazidime. We found that the metronidazole, not an anti-pseudomonal antibiotic given to the first patient infected with S-Pae, triggered the SOS response that subsequently activated the integrase IntI1 expression. This resulted in the rearrangement of the integron gene cassette array, through excision of the gcuF1 cassette, and the full expression the β-lactamase in an isolate R-Pae highly resistant to ceftazidime, which further spread to other patients within our hospital. Our results demonstrate that in human hosts, the antibiotic-induced SOS response in pathogens could play a pivotal role in adaptation process of the bacteria.

Autor: Didier Hocquet - Catherine Llanes - Michelle Thouverez - Hemantha D Kulasekara - Xavier Bertrand - Patrick Plésiat - Didier Maze

Fuente: https://hal.archives-ouvertes.fr/


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