Comparative Genomics Reveals a Well-Conserved Intrinsic Resistome in the Emerging Multidrug-Resistant Pathogen <named-content content-type="genus-species">Cupriavidus gilardii</named-content>

ABSTRACT The Gram-negative bacterium Cupriavidus gilardii is an emerging multidrug-resistant pathogen found in many environments. However, little is known about this species or its antibiotic resistance mechanisms. We used biochemical tests, antibiotic susceptibility experiments, and whole-genome se...

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Autores principales:	Cristian Ruiz, Ashley McCarley, Manuel Luis Espejo, Kerry K. Cooper, Dana E. Harmon
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Cupriavidus Cupriavidus gilardii antibiotic resistance carbapenems aminoglycosides Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/759e7c3071e948ff8e70e7c5d92448d9
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spelling	oai:doaj.org-article:759e7c3071e948ff8e70e7c5d92448d92021-11-15T15:27:33ZComparative Genomics Reveals a Well-Conserved Intrinsic Resistome in the Emerging Multidrug-Resistant Pathogen <named-content content-type="genus-species">Cupriavidus gilardii</named-content>10.1128/mSphere.00631-192379-5042https://doaj.org/article/759e7c3071e948ff8e70e7c5d92448d92019-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00631-19https://doaj.org/toc/2379-5042ABSTRACT The Gram-negative bacterium Cupriavidus gilardii is an emerging multidrug-resistant pathogen found in many environments. However, little is known about this species or its antibiotic resistance mechanisms. We used biochemical tests, antibiotic susceptibility experiments, and whole-genome sequencing to characterize an environmental C. gilardii isolate. Like clinical isolates, this isolate was resistant to meropenem, gentamicin, and other antibiotics. Resistance to these antibiotics appeared to be related to the large number of intrinsic antibiotic resistance genes found in this isolate. As determined by comparative genomics, this resistome was also well conserved in the only two other C. gilardii strains sequenced to date. The intrinsic resistome of C. gilardii did not include the colistin resistance gene mcr-5, which was in a transposon present only in one strain. The intrinsic resistome of C. gilardii was comprised of (i) many multidrug efflux pumps, such as a homolog of the Pseudomonas aeruginosa MexAB-OprM pump that may be involved in resistance to meropenem, other β-lactams, and aminoglycosides; (ii) a novel β-lactamase (OXA-837) that decreases susceptibility to ampicillin but not to other β-lactams tested; (iii) a new aminoglycoside 3-N-acetyltransferase [AAC(3)-IVb, AacC10] that decreases susceptibility to gentamicin and tobramycin; and (iv) a novel partially conserved aminoglycoside 3ʺ-adenylyltransferase [ANT(3ʺ)-Ib, AadA32] that decreases susceptibility to spectinomycin and streptomycin. These findings provide the first mechanistic insight into the intrinsic resistance of C. gilardii to multiple antibiotics and its ability to become resistant to an increasing number of drugs during therapy. IMPORTANCE Cupriavidus gilardii is a bacterium that is gaining increasing attention both as an infectious agent and because of its potential use in the detoxification of toxic compounds and other biotechnological applications. In recent years, however, there has been an increasing number of reported infections, some of them fatal, caused by C. gilardii. These infections are hard to treat because this bacterium is naturally resistant to many antibiotics, including last-resort antibiotics, such as carbapenems. Moreover, this bacterium often becomes resistant to additional antibiotics during therapy. However, little is known about C. gilardii and its antibiotic resistance mechanisms. The significance of our research is in providing, for the first time, whole-genome information about the natural antibiotic resistance genes found in this bacterium and their conservation among different C. gilardii strains. This information may provide new insights into the appropriate use of antibiotics in combating infections caused by this emerging pathogen.Cristian RuizAshley McCarleyManuel Luis EspejoKerry K. CooperDana E. HarmonAmerican Society for MicrobiologyarticleCupriavidusCupriavidus gilardiiantibiotic resistancecarbapenemsaminoglycosidesMicrobiologyQR1-502ENmSphere, Vol 4, Iss 5 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cupriavidus Cupriavidus gilardii antibiotic resistance carbapenems aminoglycosides Microbiology QR1-502
spellingShingle	Cupriavidus Cupriavidus gilardii antibiotic resistance carbapenems aminoglycosides Microbiology QR1-502 Cristian Ruiz Ashley McCarley Manuel Luis Espejo Kerry K. Cooper Dana E. Harmon Comparative Genomics Reveals a Well-Conserved Intrinsic Resistome in the Emerging Multidrug-Resistant Pathogen <named-content content-type="genus-species">Cupriavidus gilardii</named-content>
description	ABSTRACT The Gram-negative bacterium Cupriavidus gilardii is an emerging multidrug-resistant pathogen found in many environments. However, little is known about this species or its antibiotic resistance mechanisms. We used biochemical tests, antibiotic susceptibility experiments, and whole-genome sequencing to characterize an environmental C. gilardii isolate. Like clinical isolates, this isolate was resistant to meropenem, gentamicin, and other antibiotics. Resistance to these antibiotics appeared to be related to the large number of intrinsic antibiotic resistance genes found in this isolate. As determined by comparative genomics, this resistome was also well conserved in the only two other C. gilardii strains sequenced to date. The intrinsic resistome of C. gilardii did not include the colistin resistance gene mcr-5, which was in a transposon present only in one strain. The intrinsic resistome of C. gilardii was comprised of (i) many multidrug efflux pumps, such as a homolog of the Pseudomonas aeruginosa MexAB-OprM pump that may be involved in resistance to meropenem, other β-lactams, and aminoglycosides; (ii) a novel β-lactamase (OXA-837) that decreases susceptibility to ampicillin but not to other β-lactams tested; (iii) a new aminoglycoside 3-N-acetyltransferase [AAC(3)-IVb, AacC10] that decreases susceptibility to gentamicin and tobramycin; and (iv) a novel partially conserved aminoglycoside 3ʺ-adenylyltransferase [ANT(3ʺ)-Ib, AadA32] that decreases susceptibility to spectinomycin and streptomycin. These findings provide the first mechanistic insight into the intrinsic resistance of C. gilardii to multiple antibiotics and its ability to become resistant to an increasing number of drugs during therapy. IMPORTANCE Cupriavidus gilardii is a bacterium that is gaining increasing attention both as an infectious agent and because of its potential use in the detoxification of toxic compounds and other biotechnological applications. In recent years, however, there has been an increasing number of reported infections, some of them fatal, caused by C. gilardii. These infections are hard to treat because this bacterium is naturally resistant to many antibiotics, including last-resort antibiotics, such as carbapenems. Moreover, this bacterium often becomes resistant to additional antibiotics during therapy. However, little is known about C. gilardii and its antibiotic resistance mechanisms. The significance of our research is in providing, for the first time, whole-genome information about the natural antibiotic resistance genes found in this bacterium and their conservation among different C. gilardii strains. This information may provide new insights into the appropriate use of antibiotics in combating infections caused by this emerging pathogen.
format	article
author	Cristian Ruiz Ashley McCarley Manuel Luis Espejo Kerry K. Cooper Dana E. Harmon
author_facet	Cristian Ruiz Ashley McCarley Manuel Luis Espejo Kerry K. Cooper Dana E. Harmon
author_sort	Cristian Ruiz
title	Comparative Genomics Reveals a Well-Conserved Intrinsic Resistome in the Emerging Multidrug-Resistant Pathogen <named-content content-type="genus-species">Cupriavidus gilardii</named-content>
title_short	Comparative Genomics Reveals a Well-Conserved Intrinsic Resistome in the Emerging Multidrug-Resistant Pathogen <named-content content-type="genus-species">Cupriavidus gilardii</named-content>
title_full	Comparative Genomics Reveals a Well-Conserved Intrinsic Resistome in the Emerging Multidrug-Resistant Pathogen <named-content content-type="genus-species">Cupriavidus gilardii</named-content>
title_fullStr	Comparative Genomics Reveals a Well-Conserved Intrinsic Resistome in the Emerging Multidrug-Resistant Pathogen <named-content content-type="genus-species">Cupriavidus gilardii</named-content>
title_full_unstemmed	Comparative Genomics Reveals a Well-Conserved Intrinsic Resistome in the Emerging Multidrug-Resistant Pathogen <named-content content-type="genus-species">Cupriavidus gilardii</named-content>
title_sort	comparative genomics reveals a well-conserved intrinsic resistome in the emerging multidrug-resistant pathogen <named-content content-type="genus-species">cupriavidus gilardii</named-content>
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/759e7c3071e948ff8e70e7c5d92448d9
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Comparative Genomics Reveals a Well-Conserved Intrinsic Resistome in the Emerging Multidrug-Resistant Pathogen <named-content content-type="genus-species">Cupriavidus gilardii</named-content>

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