The Birth and Demise of the IS<italic toggle="yes">Apl1</italic>-<italic toggle="yes">mcr-1</italic>-IS<italic toggle="yes">Apl1</italic> Composite Transposon: the Vehicle for Transferable Colistin Resistance

ABSTRACT The origin and mobilization of the ~2,609-bp DNA segment containing the mobile colistin resistance gene mcr-1 continue to be sources of uncertainty, but recent evidence suggests that the gene originated in Moraxella species. Moreover mcr-1 can be mobilized as an ISApl1-flanked composite tra...

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Autores principales:	Erik Snesrud, Patrick McGann, Michael Chandler
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	colistin resistance composite transposon formation drug resistance evolution insertion sequence transposon decay Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/e4e0e330c353404487619bab544b0d0d
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spelling	oai:doaj.org-article:e4e0e330c353404487619bab544b0d0d2021-11-15T15:53:26ZThe Birth and Demise of the IS<italic toggle="yes">Apl1</italic>-<italic toggle="yes">mcr-1</italic>-IS<italic toggle="yes">Apl1</italic> Composite Transposon: the Vehicle for Transferable Colistin Resistance10.1128/mBio.02381-172150-7511https://doaj.org/article/e4e0e330c353404487619bab544b0d0d2018-03-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02381-17https://doaj.org/toc/2150-7511ABSTRACT The origin and mobilization of the ~2,609-bp DNA segment containing the mobile colistin resistance gene mcr-1 continue to be sources of uncertainty, but recent evidence suggests that the gene originated in Moraxella species. Moreover mcr-1 can be mobilized as an ISApl1-flanked composite transposon (Tn6330), but many sequences have been identified without ISApl1 or with just a single copy (single ended). To further clarify the origins and mobilization of mcr-1, we employed the Geneious R8 software suite to comprehensively analyze the genetic environment of every complete mcr-1 structure deposited in GenBank as of this writing (September 2017) both with and without associated ISApl1 (n = 273). This revealed that the 2,609-bp mcr-1 structure was likely mobilized from a close relative of a novel species of Moraxella containing a chromosomal region sharing >96% nucleotide identity with the canonical sequence. This chromosomal region is bounded by AT and CG dinucleotides, which have been described on the inside ends (IE) of all intact Tn6330 described to date and represent the ancestral 2-bp target site duplications (TSDs) generated by ISApl1 transposition. We further demonstrate that all mcr-1 structures with just one ISApl1 copy or with no ISApl1 copies were formed by deletion of ISApl1 from the ancestral Tn6330, likely by a process related to the “copy-out–paste-in” transposition mechanism. Finally, we show that only the rare examples of single-ended structures that have retained a portion of the excised downstream ISApl1 including the entire inverted right repeat might be capable of mobilization. IMPORTANCE A comprehensive analysis of all intact mcr-1 sequences in GenBank was used to identify a region on the chromosome of a novel Moraxella species with remarkable homology to the canonical mcr-1 structure and that likely represents the origin of this important gene. These data also demonstrate that all mcr-1 structures lacking one or both flanking ISApl1 were formed from ancestral composite transposons that subsequently lost the insertion sequences by a process of abortive transposition. This observation conclusively shows that mobilization of mcr-1 occurs as part of a composite transposon and that structures lacking the downstream ISApl1 are not capable of mobilization.Erik SnesrudPatrick McGannMichael ChandlerAmerican Society for Microbiologyarticlecolistin resistancecomposite transposon formationdrug resistance evolutioninsertion sequencetransposon decayMicrobiologyQR1-502ENmBio, Vol 9, Iss 1 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	colistin resistance composite transposon formation drug resistance evolution insertion sequence transposon decay Microbiology QR1-502
spellingShingle	colistin resistance composite transposon formation drug resistance evolution insertion sequence transposon decay Microbiology QR1-502 Erik Snesrud Patrick McGann Michael Chandler The Birth and Demise of the IS<italic toggle="yes">Apl1</italic>-<italic toggle="yes">mcr-1</italic>-IS<italic toggle="yes">Apl1</italic> Composite Transposon: the Vehicle for Transferable Colistin Resistance
description	ABSTRACT The origin and mobilization of the ~2,609-bp DNA segment containing the mobile colistin resistance gene mcr-1 continue to be sources of uncertainty, but recent evidence suggests that the gene originated in Moraxella species. Moreover mcr-1 can be mobilized as an ISApl1-flanked composite transposon (Tn6330), but many sequences have been identified without ISApl1 or with just a single copy (single ended). To further clarify the origins and mobilization of mcr-1, we employed the Geneious R8 software suite to comprehensively analyze the genetic environment of every complete mcr-1 structure deposited in GenBank as of this writing (September 2017) both with and without associated ISApl1 (n = 273). This revealed that the 2,609-bp mcr-1 structure was likely mobilized from a close relative of a novel species of Moraxella containing a chromosomal region sharing >96% nucleotide identity with the canonical sequence. This chromosomal region is bounded by AT and CG dinucleotides, which have been described on the inside ends (IE) of all intact Tn6330 described to date and represent the ancestral 2-bp target site duplications (TSDs) generated by ISApl1 transposition. We further demonstrate that all mcr-1 structures with just one ISApl1 copy or with no ISApl1 copies were formed by deletion of ISApl1 from the ancestral Tn6330, likely by a process related to the “copy-out–paste-in” transposition mechanism. Finally, we show that only the rare examples of single-ended structures that have retained a portion of the excised downstream ISApl1 including the entire inverted right repeat might be capable of mobilization. IMPORTANCE A comprehensive analysis of all intact mcr-1 sequences in GenBank was used to identify a region on the chromosome of a novel Moraxella species with remarkable homology to the canonical mcr-1 structure and that likely represents the origin of this important gene. These data also demonstrate that all mcr-1 structures lacking one or both flanking ISApl1 were formed from ancestral composite transposons that subsequently lost the insertion sequences by a process of abortive transposition. This observation conclusively shows that mobilization of mcr-1 occurs as part of a composite transposon and that structures lacking the downstream ISApl1 are not capable of mobilization.
format	article
author	Erik Snesrud Patrick McGann Michael Chandler
author_facet	Erik Snesrud Patrick McGann Michael Chandler
author_sort	Erik Snesrud
title	The Birth and Demise of the IS<italic toggle="yes">Apl1</italic>-<italic toggle="yes">mcr-1</italic>-IS<italic toggle="yes">Apl1</italic> Composite Transposon: the Vehicle for Transferable Colistin Resistance
title_short	The Birth and Demise of the IS<italic toggle="yes">Apl1</italic>-<italic toggle="yes">mcr-1</italic>-IS<italic toggle="yes">Apl1</italic> Composite Transposon: the Vehicle for Transferable Colistin Resistance
title_full	The Birth and Demise of the IS<italic toggle="yes">Apl1</italic>-<italic toggle="yes">mcr-1</italic>-IS<italic toggle="yes">Apl1</italic> Composite Transposon: the Vehicle for Transferable Colistin Resistance
title_fullStr	The Birth and Demise of the IS<italic toggle="yes">Apl1</italic>-<italic toggle="yes">mcr-1</italic>-IS<italic toggle="yes">Apl1</italic> Composite Transposon: the Vehicle for Transferable Colistin Resistance
title_full_unstemmed	The Birth and Demise of the IS<italic toggle="yes">Apl1</italic>-<italic toggle="yes">mcr-1</italic>-IS<italic toggle="yes">Apl1</italic> Composite Transposon: the Vehicle for Transferable Colistin Resistance
title_sort	birth and demise of the is<italic toggle="yes">apl1</italic>-<italic toggle="yes">mcr-1</italic>-is<italic toggle="yes">apl1</italic> composite transposon: the vehicle for transferable colistin resistance
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/e4e0e330c353404487619bab544b0d0d
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The Birth and Demise of the IS<italic toggle="yes">Apl1</italic>-<italic toggle="yes">mcr-1</italic>-IS<italic toggle="yes">Apl1</italic> Composite Transposon: the Vehicle for Transferable Colistin Resistance

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