Movement of IS<italic toggle="yes">26</italic>-Associated Antibiotic Resistance Genes Occurs via a Translocatable Unit That Includes a Single IS<italic toggle="yes">26</italic> and Preferentially Inserts Adjacent to Another IS<italic toggle="yes">26</italic>

ABSTRACT The insertion sequence IS26 plays a key role in disseminating antibiotic resistance genes in Gram-negative bacteria, forming regions containing more than one antibiotic resistance gene that are flanked by and interspersed with copies of IS26. A model presented for a second mode of IS26 move...

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Autores principales:	Christopher J. Harmer, Robert A. Moran, Ruth M. Hall
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2014
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/195bfc43e01748839b04e0a4ca4932c5
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spelling	oai:doaj.org-article:195bfc43e01748839b04e0a4ca4932c52021-11-15T15:45:54ZMovement of IS<italic toggle="yes">26</italic>-Associated Antibiotic Resistance Genes Occurs via a Translocatable Unit That Includes a Single IS<italic toggle="yes">26</italic> and Preferentially Inserts Adjacent to Another IS<italic toggle="yes">26</italic>10.1128/mBio.01801-142150-7511https://doaj.org/article/195bfc43e01748839b04e0a4ca4932c52014-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01801-14https://doaj.org/toc/2150-7511ABSTRACT The insertion sequence IS26 plays a key role in disseminating antibiotic resistance genes in Gram-negative bacteria, forming regions containing more than one antibiotic resistance gene that are flanked by and interspersed with copies of IS26. A model presented for a second mode of IS26 movement that explains the structure of these regions involves a translocatable unit consisting of a unique DNA segment carrying an antibiotic resistance (or other) gene and a single IS copy. Structures resembling class I transposons are generated via RecA-independent incorporation of a translocatable unit next to a second IS26 such that the ISs are in direct orientation. Repeating this process would lead to arrays of resistance genes with directly oriented copies of IS26 at each end and between each unique segment. This model requires that IS26 recognizes another IS26 as a target, and in transposition experiments, the frequency of cointegrate formation was 60-fold higher when the target plasmid contained IS26. This reaction was conservative, with no additional IS26 or target site duplication generated, and orientation specific as the IS26s in the cointegrates were always in the same orientation. Consequently, the cointegrates were identical to those formed via the known mode of IS26 movement when a target IS26 was not present. Intact transposase genes in both IS26s were required for high-frequency cointegrate formation as inactivation of either one reduced the frequency 30-fold. However, the IS26 target specificity was retained. Conversion of each residue in the DDE motif of the Tnp26 transposase also reduced the cointegration frequency. IMPORTANCE Resistance to antibiotics belonging to several of the different classes used to treat infections is a critical problem. Multiply antibiotic-resistant bacteria usually carry large regions containing several antibiotic resistance genes, and in Gram-negative bacteria, IS26 is often seen in these clusters. A model to explain the unusual structure of regions containing multiple IS26 copies, each associated with a resistance gene, was not available, and the mechanism of their formation was unexplored. IS26-flanked structures deceptively resemble class I transposons, but this work reveals that the features of IS26 movement do not resemble those of the IS and class I transposons studied to date. IS26 uses a novel movement mechanism that defines a new family of mobile genetic elements that we have called “translocatable units.” The IS26 mechanism also explains the properties of IS257 (IS431) and IS1216, which belong to the same IS family and mobilize resistance genes in Gram-positive staphylococci and enterococci.Christopher J. HarmerRobert A. MoranRuth M. HallAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 5, Iss 5 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Christopher J. Harmer Robert A. Moran Ruth M. Hall Movement of IS<italic toggle="yes">26</italic>-Associated Antibiotic Resistance Genes Occurs via a Translocatable Unit That Includes a Single IS<italic toggle="yes">26</italic> and Preferentially Inserts Adjacent to Another IS<italic toggle="yes">26</italic>
description	ABSTRACT The insertion sequence IS26 plays a key role in disseminating antibiotic resistance genes in Gram-negative bacteria, forming regions containing more than one antibiotic resistance gene that are flanked by and interspersed with copies of IS26. A model presented for a second mode of IS26 movement that explains the structure of these regions involves a translocatable unit consisting of a unique DNA segment carrying an antibiotic resistance (or other) gene and a single IS copy. Structures resembling class I transposons are generated via RecA-independent incorporation of a translocatable unit next to a second IS26 such that the ISs are in direct orientation. Repeating this process would lead to arrays of resistance genes with directly oriented copies of IS26 at each end and between each unique segment. This model requires that IS26 recognizes another IS26 as a target, and in transposition experiments, the frequency of cointegrate formation was 60-fold higher when the target plasmid contained IS26. This reaction was conservative, with no additional IS26 or target site duplication generated, and orientation specific as the IS26s in the cointegrates were always in the same orientation. Consequently, the cointegrates were identical to those formed via the known mode of IS26 movement when a target IS26 was not present. Intact transposase genes in both IS26s were required for high-frequency cointegrate formation as inactivation of either one reduced the frequency 30-fold. However, the IS26 target specificity was retained. Conversion of each residue in the DDE motif of the Tnp26 transposase also reduced the cointegration frequency. IMPORTANCE Resistance to antibiotics belonging to several of the different classes used to treat infections is a critical problem. Multiply antibiotic-resistant bacteria usually carry large regions containing several antibiotic resistance genes, and in Gram-negative bacteria, IS26 is often seen in these clusters. A model to explain the unusual structure of regions containing multiple IS26 copies, each associated with a resistance gene, was not available, and the mechanism of their formation was unexplored. IS26-flanked structures deceptively resemble class I transposons, but this work reveals that the features of IS26 movement do not resemble those of the IS and class I transposons studied to date. IS26 uses a novel movement mechanism that defines a new family of mobile genetic elements that we have called “translocatable units.” The IS26 mechanism also explains the properties of IS257 (IS431) and IS1216, which belong to the same IS family and mobilize resistance genes in Gram-positive staphylococci and enterococci.
format	article
author	Christopher J. Harmer Robert A. Moran Ruth M. Hall
author_facet	Christopher J. Harmer Robert A. Moran Ruth M. Hall
author_sort	Christopher J. Harmer
title	Movement of IS<italic toggle="yes">26</italic>-Associated Antibiotic Resistance Genes Occurs via a Translocatable Unit That Includes a Single IS<italic toggle="yes">26</italic> and Preferentially Inserts Adjacent to Another IS<italic toggle="yes">26</italic>
title_short	Movement of IS<italic toggle="yes">26</italic>-Associated Antibiotic Resistance Genes Occurs via a Translocatable Unit That Includes a Single IS<italic toggle="yes">26</italic> and Preferentially Inserts Adjacent to Another IS<italic toggle="yes">26</italic>
title_full	Movement of IS<italic toggle="yes">26</italic>-Associated Antibiotic Resistance Genes Occurs via a Translocatable Unit That Includes a Single IS<italic toggle="yes">26</italic> and Preferentially Inserts Adjacent to Another IS<italic toggle="yes">26</italic>
title_fullStr	Movement of IS<italic toggle="yes">26</italic>-Associated Antibiotic Resistance Genes Occurs via a Translocatable Unit That Includes a Single IS<italic toggle="yes">26</italic> and Preferentially Inserts Adjacent to Another IS<italic toggle="yes">26</italic>
title_full_unstemmed	Movement of IS<italic toggle="yes">26</italic>-Associated Antibiotic Resistance Genes Occurs via a Translocatable Unit That Includes a Single IS<italic toggle="yes">26</italic> and Preferentially Inserts Adjacent to Another IS<italic toggle="yes">26</italic>
title_sort	movement of is<italic toggle="yes">26</italic>-associated antibiotic resistance genes occurs via a translocatable unit that includes a single is<italic toggle="yes">26</italic> and preferentially inserts adjacent to another is<italic toggle="yes">26</italic>
publisher	American Society for Microbiology
publishDate	2014
url	https://doaj.org/article/195bfc43e01748839b04e0a4ca4932c5
work_keys_str_mv	AT christopherjharmer movementofisitalictoggleyes26italicassociatedantibioticresistancegenesoccursviaatranslocatableunitthatincludesasingleisitalictoggleyes26italicandpreferentiallyinsertsadjacenttoanotherisitalictoggleyes26italic AT robertamoran movementofisitalictoggleyes26italicassociatedantibioticresistancegenesoccursviaatranslocatableunitthatincludesasingleisitalictoggleyes26italicandpreferentiallyinsertsadjacenttoanotherisitalictoggleyes26italic AT ruthmhall movementofisitalictoggleyes26italicassociatedantibioticresistancegenesoccursviaatranslocatableunitthatincludesasingleisitalictoggleyes26italicandpreferentiallyinsertsadjacenttoanotherisitalictoggleyes26italic
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Movement of IS<italic toggle="yes">26</italic>-Associated Antibiotic Resistance Genes Occurs via a Translocatable Unit That Includes a Single IS<italic toggle="yes">26</italic> and Preferentially Inserts Adjacent to Another IS<italic toggle="yes">26</italic>

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