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

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, leadi...

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Autores principales:	Didier Hocquet, Catherine Llanes, Michelle Thouverez, Hemantha D Kulasekara, Xavier Bertrand, Patrick Plésiat, Didier Mazel, Samuel I Miller
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/3aeb1e49cba34d9b96248d4b1d76f965
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spelling	oai:doaj.org-article:3aeb1e49cba34d9b96248d4b1d76f9652021-11-18T06:04:18ZEvidence for induction of integron-based antibiotic resistance by the SOS response in a clinical setting.1553-73661553-737410.1371/journal.ppat.1002778https://doaj.org/article/3aeb1e49cba34d9b96248d4b1d76f9652012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22719259/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Bacterial 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 bla(OXA-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.Didier HocquetCatherine LlanesMichelle ThouverezHemantha D KulasekaraXavier BertrandPatrick PlésiatDidier MazelSamuel I MillerPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 8, Iss 6, p e1002778 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Didier Hocquet Catherine Llanes Michelle Thouverez Hemantha D Kulasekara Xavier Bertrand Patrick Plésiat Didier Mazel Samuel I Miller Evidence for induction of integron-based antibiotic resistance by the SOS response in a clinical setting.
description	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 bla(OXA-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.
format	article
author	Didier Hocquet Catherine Llanes Michelle Thouverez Hemantha D Kulasekara Xavier Bertrand Patrick Plésiat Didier Mazel Samuel I Miller
author_facet	Didier Hocquet Catherine Llanes Michelle Thouverez Hemantha D Kulasekara Xavier Bertrand Patrick Plésiat Didier Mazel Samuel I Miller
author_sort	Didier Hocquet
title	Evidence for induction of integron-based antibiotic resistance by the SOS response in a clinical setting.
title_short	Evidence for induction of integron-based antibiotic resistance by the SOS response in a clinical setting.
title_full	Evidence for induction of integron-based antibiotic resistance by the SOS response in a clinical setting.
title_fullStr	Evidence for induction of integron-based antibiotic resistance by the SOS response in a clinical setting.
title_full_unstemmed	Evidence for induction of integron-based antibiotic resistance by the SOS response in a clinical setting.
title_sort	evidence for induction of integron-based antibiotic resistance by the sos response in a clinical setting.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/3aeb1e49cba34d9b96248d4b1d76f965
work_keys_str_mv	AT didierhocquet evidenceforinductionofintegronbasedantibioticresistancebythesosresponseinaclinicalsetting AT catherinellanes evidenceforinductionofintegronbasedantibioticresistancebythesosresponseinaclinicalsetting AT michellethouverez evidenceforinductionofintegronbasedantibioticresistancebythesosresponseinaclinicalsetting AT hemanthadkulasekara evidenceforinductionofintegronbasedantibioticresistancebythesosresponseinaclinicalsetting AT xavierbertrand evidenceforinductionofintegronbasedantibioticresistancebythesosresponseinaclinicalsetting AT patrickplesiat evidenceforinductionofintegronbasedantibioticresistancebythesosresponseinaclinicalsetting AT didiermazel evidenceforinductionofintegronbasedantibioticresistancebythesosresponseinaclinicalsetting AT samuelimiller evidenceforinductionofintegronbasedantibioticresistancebythesosresponseinaclinicalsetting
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Evidence for induction of integron-based antibiotic resistance by the SOS response in a clinical setting.

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