Origin in <named-content content-type="genus-species">Acinetobacter guillouiae</named-content> and Dissemination of the Aminoglycoside-Modifying Enzyme Aph(3′)-VI

ABSTRACT The amikacin resistance gene aphA6 was first detected in the nosocomial pathogen Acinetobacter baumannii and subsequently in other genera. Analysis of 133 whole-genome sequences covering the taxonomic diversity of Acinetobacter spp. detected aphA6 in the chromosome of 2 isolates of A. guill...

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Autores principales:	Eun-Jeong Yoon, Sylvie Goussard, Marie Touchon, Lenka Krizova, Gustavo Cerqueira, Cheryl Murphy, Thierry Lambert, Catherine Grillot-Courvalin, Alexandr Nemec, Patrice Courvalin
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2014
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/4de100c73641403b9da21d94f82f746b
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spelling	oai:doaj.org-article:4de100c73641403b9da21d94f82f746b2021-11-15T15:45:54ZOrigin in <named-content content-type="genus-species">Acinetobacter guillouiae</named-content> and Dissemination of the Aminoglycoside-Modifying Enzyme Aph(3′)-VI10.1128/mBio.01972-142150-7511https://doaj.org/article/4de100c73641403b9da21d94f82f746b2014-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01972-14https://doaj.org/toc/2150-7511ABSTRACT The amikacin resistance gene aphA6 was first detected in the nosocomial pathogen Acinetobacter baumannii and subsequently in other genera. Analysis of 133 whole-genome sequences covering the taxonomic diversity of Acinetobacter spp. detected aphA6 in the chromosome of 2 isolates of A. guillouiae, which is an environmental species, 1 of 8 A. parvus isolates, and 5 of 34 A. baumannii isolates. The gene was also present in 29 out of 36 A. guillouiae isolates screened by PCR, indicating that it is ancestral to this species. The Pnative promoter for aphA6 in A. guillouiae and A. parvus was replaced in A. baumannii by PaphA6, which was generated by use of the insertion sequence ISAba125, which brought a −35 sequence. Study of promoter strength in Escherichia coli and A. baumannii indicated that PaphA6 was four times more potent than Pnative. There was a good correlation between aminoglycoside MICs and aphA6 transcription in A. guillouiae isolates that remained susceptible to amikacin. The marked topology differences of the phylogenetic trees of aphA6 and of the hosts strongly support its recent direct transfer within Acinetobacter spp. and also to evolutionarily remote bacterial genera. Concomitant expression of aphA6 must have occurred because, contrary to the donors, it can confer resistance to the new hosts. Mobilization and expression of aphA6 via composite transposons and the upstream IS-generating hybrid PaphA6, followed by conjugation, seems the most plausible mechanism. This is in agreement with the observation that, in the recipients, aphA6 is carried by conjugative plasmids and flanked by IS that are common in Acinetobacter spp. Our data indicate that resistance genes can also be found in susceptible environmental bacteria. IMPORTANCE We speculated that the aphA6 gene for an enzyme that confers resistance to amikacin, the most active aminoglycoside for the treatment of nosocomial infections due to Acinetobacter spp., originated in this genus before disseminating to phylogenetically distant genera pathogenic for humans. Using a combination of whole-genome sequencing of a collection of Acinetobacter spp. covering the breadth of the known taxonomic diversity of the genus, gene cloning, detailed promoter analysis, study of heterologous gene expression, and comparative analysis of the phylogenetic trees of aphA6 and of the bacterial hosts, we found that aphA6 originated in Acinetobacter guillouiae, an amikacin-susceptible environmental species. The gene conferred, upon mobilization, high-level resistance to the new hosts. This work stresses that nonpathogenic bacteria can act as reservoirs of resistance determinants, and it provides an example of the use of a genomic library to study the origin and dissemination of an antibiotic resistance gene to human pathogens.Eun-Jeong YoonSylvie GoussardMarie TouchonLenka KrizovaGustavo CerqueiraCheryl MurphyThierry LambertCatherine Grillot-CourvalinAlexandr NemecPatrice CourvalinAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 5, Iss 5 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Eun-Jeong Yoon Sylvie Goussard Marie Touchon Lenka Krizova Gustavo Cerqueira Cheryl Murphy Thierry Lambert Catherine Grillot-Courvalin Alexandr Nemec Patrice Courvalin Origin in <named-content content-type="genus-species">Acinetobacter guillouiae</named-content> and Dissemination of the Aminoglycoside-Modifying Enzyme Aph(3′)-VI
description	ABSTRACT The amikacin resistance gene aphA6 was first detected in the nosocomial pathogen Acinetobacter baumannii and subsequently in other genera. Analysis of 133 whole-genome sequences covering the taxonomic diversity of Acinetobacter spp. detected aphA6 in the chromosome of 2 isolates of A. guillouiae, which is an environmental species, 1 of 8 A. parvus isolates, and 5 of 34 A. baumannii isolates. The gene was also present in 29 out of 36 A. guillouiae isolates screened by PCR, indicating that it is ancestral to this species. The Pnative promoter for aphA6 in A. guillouiae and A. parvus was replaced in A. baumannii by PaphA6, which was generated by use of the insertion sequence ISAba125, which brought a −35 sequence. Study of promoter strength in Escherichia coli and A. baumannii indicated that PaphA6 was four times more potent than Pnative. There was a good correlation between aminoglycoside MICs and aphA6 transcription in A. guillouiae isolates that remained susceptible to amikacin. The marked topology differences of the phylogenetic trees of aphA6 and of the hosts strongly support its recent direct transfer within Acinetobacter spp. and also to evolutionarily remote bacterial genera. Concomitant expression of aphA6 must have occurred because, contrary to the donors, it can confer resistance to the new hosts. Mobilization and expression of aphA6 via composite transposons and the upstream IS-generating hybrid PaphA6, followed by conjugation, seems the most plausible mechanism. This is in agreement with the observation that, in the recipients, aphA6 is carried by conjugative plasmids and flanked by IS that are common in Acinetobacter spp. Our data indicate that resistance genes can also be found in susceptible environmental bacteria. IMPORTANCE We speculated that the aphA6 gene for an enzyme that confers resistance to amikacin, the most active aminoglycoside for the treatment of nosocomial infections due to Acinetobacter spp., originated in this genus before disseminating to phylogenetically distant genera pathogenic for humans. Using a combination of whole-genome sequencing of a collection of Acinetobacter spp. covering the breadth of the known taxonomic diversity of the genus, gene cloning, detailed promoter analysis, study of heterologous gene expression, and comparative analysis of the phylogenetic trees of aphA6 and of the bacterial hosts, we found that aphA6 originated in Acinetobacter guillouiae, an amikacin-susceptible environmental species. The gene conferred, upon mobilization, high-level resistance to the new hosts. This work stresses that nonpathogenic bacteria can act as reservoirs of resistance determinants, and it provides an example of the use of a genomic library to study the origin and dissemination of an antibiotic resistance gene to human pathogens.
format	article
author	Eun-Jeong Yoon Sylvie Goussard Marie Touchon Lenka Krizova Gustavo Cerqueira Cheryl Murphy Thierry Lambert Catherine Grillot-Courvalin Alexandr Nemec Patrice Courvalin
author_facet	Eun-Jeong Yoon Sylvie Goussard Marie Touchon Lenka Krizova Gustavo Cerqueira Cheryl Murphy Thierry Lambert Catherine Grillot-Courvalin Alexandr Nemec Patrice Courvalin
author_sort	Eun-Jeong Yoon
title	Origin in <named-content content-type="genus-species">Acinetobacter guillouiae</named-content> and Dissemination of the Aminoglycoside-Modifying Enzyme Aph(3′)-VI
title_short	Origin in <named-content content-type="genus-species">Acinetobacter guillouiae</named-content> and Dissemination of the Aminoglycoside-Modifying Enzyme Aph(3′)-VI
title_full	Origin in <named-content content-type="genus-species">Acinetobacter guillouiae</named-content> and Dissemination of the Aminoglycoside-Modifying Enzyme Aph(3′)-VI
title_fullStr	Origin in <named-content content-type="genus-species">Acinetobacter guillouiae</named-content> and Dissemination of the Aminoglycoside-Modifying Enzyme Aph(3′)-VI
title_full_unstemmed	Origin in <named-content content-type="genus-species">Acinetobacter guillouiae</named-content> and Dissemination of the Aminoglycoside-Modifying Enzyme Aph(3′)-VI
title_sort	origin in <named-content content-type="genus-species">acinetobacter guillouiae</named-content> and dissemination of the aminoglycoside-modifying enzyme aph(3′)-vi
publisher	American Society for Microbiology
publishDate	2014
url	https://doaj.org/article/4de100c73641403b9da21d94f82f746b
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Origin in <named-content content-type="genus-species">Acinetobacter guillouiae</named-content> and Dissemination of the Aminoglycoside-Modifying Enzyme Aph(3′)-VI

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