The <named-content content-type="genus-species">Galleria mellonella</named-content> Infection Model Does Not Accurately Differentiate between Hypervirulent and Classical <named-content content-type="genus-species">Klebsiella pneumoniae</named-content>

ABSTRACT Hypervirulent Klebsiella pneumoniae (hvKp) is an emerging pathogen of increasing concern due to its ability to cause serious organ and life-threatening infections in healthy individuals and its increasing acquisition of antimicrobial resistance determinants. Identification of hvKp is critic...

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Autores principales:	Thomas A. Russo, Ulrike MacDonald
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Galleria mellonella infection model classical Klebsiella pneumoniae hypervirulent Klebsiella pneumoniae infection models outbred mouse systemic infection model virulence Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/f5525bccdbaf46598571854b9c74de9e
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spelling	oai:doaj.org-article:f5525bccdbaf46598571854b9c74de9e2021-11-15T15:27:53ZThe <named-content content-type="genus-species">Galleria mellonella</named-content> Infection Model Does Not Accurately Differentiate between Hypervirulent and Classical <named-content content-type="genus-species">Klebsiella pneumoniae</named-content>10.1128/mSphere.00850-192379-5042https://doaj.org/article/f5525bccdbaf46598571854b9c74de9e2020-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00850-19https://doaj.org/toc/2379-5042ABSTRACT Hypervirulent Klebsiella pneumoniae (hvKp) is an emerging pathogen of increasing concern due to its ability to cause serious organ and life-threatening infections in healthy individuals and its increasing acquisition of antimicrobial resistance determinants. Identification of hvKp is critical for patient care and epidemiologic and research studies. Five genotypic markers on the hvKp-specific virulence plasmid can accurately differentiate hvKp from the less virulent classical K. pneumoniae (cKp) strain, but it is unclear whether the possession of fewer markers accurately predicts the hvKp pathotype. Likewise, the effect, if any, of various antimicrobial resistance factors on the pathogenic potential of hvKp has been incompletely explored. The Galleria mellonella infection model is often used to assess virulence, but this tool has not been validated. Therefore, levels of lethality of defined hvKp and cKp strain cohorts were compared in Galleria and outbred mouse models. The murine model, but not the G. mellonella model, accurately differentiated hvKp from cKp strains. Therefore, isolates in which the pathogenic potential is ambiguous due to an incomplete hvKp biomarker profile, an incomplete pLVPK-like hvKp-specific virulence plasmid, antimicrobial resistance that could decrease biofitness, and/or the lack of a characteristic clinical presentation should be validated in an outbred murine model. These data will assist in determining the minimal genomic content needed for full expression of the hypervirulence phenotype. This information, in turn, is critical for the development of the pragmatic point-of-care testing requisite for patient care and for the performance of epidemiologic and research studies going forward. IMPORTANCE Hypervirulent Klebsiella pneumoniae (hvKp) is of increasing concern because it can infect individuals in community and health care settings and because such infections are becoming difficult to treat. Identification of hvKp is important for patient care and to track its global spread. The genetic definition of hvKp, which can be used for its identification and the development of diagnostic tests, has not been optimized. Determination of possession of 4 of 5 genes that are present on the hvKp-specific virulence plasmid is highly accurate for identifying hvKp. However, an ongoing issue is whether strains that possess only some of these markers are still hypervirulent. The Galleria mellonella model and, less commonly, the murine infection model have been used to assess the virulence of these ambiguously identifiable strains. This report demonstrates that the murine model but not the G. mellonella model accurately identifies suspected hvKp strains. This information is critical for the development of diagnostics for patient care and for future research studies.Thomas A. RussoUlrike MacDonaldAmerican Society for MicrobiologyarticleGalleria mellonella infection modelclassical Klebsiella pneumoniaehypervirulent Klebsiella pneumoniaeinfection modelsoutbred mouse systemic infection modelvirulenceMicrobiologyQR1-502ENmSphere, Vol 5, Iss 1 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Galleria mellonella infection model classical Klebsiella pneumoniae hypervirulent Klebsiella pneumoniae infection models outbred mouse systemic infection model virulence Microbiology QR1-502
spellingShingle	Galleria mellonella infection model classical Klebsiella pneumoniae hypervirulent Klebsiella pneumoniae infection models outbred mouse systemic infection model virulence Microbiology QR1-502 Thomas A. Russo Ulrike MacDonald The <named-content content-type="genus-species">Galleria mellonella</named-content> Infection Model Does Not Accurately Differentiate between Hypervirulent and Classical <named-content content-type="genus-species">Klebsiella pneumoniae</named-content>
description	ABSTRACT Hypervirulent Klebsiella pneumoniae (hvKp) is an emerging pathogen of increasing concern due to its ability to cause serious organ and life-threatening infections in healthy individuals and its increasing acquisition of antimicrobial resistance determinants. Identification of hvKp is critical for patient care and epidemiologic and research studies. Five genotypic markers on the hvKp-specific virulence plasmid can accurately differentiate hvKp from the less virulent classical K. pneumoniae (cKp) strain, but it is unclear whether the possession of fewer markers accurately predicts the hvKp pathotype. Likewise, the effect, if any, of various antimicrobial resistance factors on the pathogenic potential of hvKp has been incompletely explored. The Galleria mellonella infection model is often used to assess virulence, but this tool has not been validated. Therefore, levels of lethality of defined hvKp and cKp strain cohorts were compared in Galleria and outbred mouse models. The murine model, but not the G. mellonella model, accurately differentiated hvKp from cKp strains. Therefore, isolates in which the pathogenic potential is ambiguous due to an incomplete hvKp biomarker profile, an incomplete pLVPK-like hvKp-specific virulence plasmid, antimicrobial resistance that could decrease biofitness, and/or the lack of a characteristic clinical presentation should be validated in an outbred murine model. These data will assist in determining the minimal genomic content needed for full expression of the hypervirulence phenotype. This information, in turn, is critical for the development of the pragmatic point-of-care testing requisite for patient care and for the performance of epidemiologic and research studies going forward. IMPORTANCE Hypervirulent Klebsiella pneumoniae (hvKp) is of increasing concern because it can infect individuals in community and health care settings and because such infections are becoming difficult to treat. Identification of hvKp is important for patient care and to track its global spread. The genetic definition of hvKp, which can be used for its identification and the development of diagnostic tests, has not been optimized. Determination of possession of 4 of 5 genes that are present on the hvKp-specific virulence plasmid is highly accurate for identifying hvKp. However, an ongoing issue is whether strains that possess only some of these markers are still hypervirulent. The Galleria mellonella model and, less commonly, the murine infection model have been used to assess the virulence of these ambiguously identifiable strains. This report demonstrates that the murine model but not the G. mellonella model accurately identifies suspected hvKp strains. This information is critical for the development of diagnostics for patient care and for future research studies.
format	article
author	Thomas A. Russo Ulrike MacDonald
author_facet	Thomas A. Russo Ulrike MacDonald
author_sort	Thomas A. Russo
title	The <named-content content-type="genus-species">Galleria mellonella</named-content> Infection Model Does Not Accurately Differentiate between Hypervirulent and Classical <named-content content-type="genus-species">Klebsiella pneumoniae</named-content>
title_short	The <named-content content-type="genus-species">Galleria mellonella</named-content> Infection Model Does Not Accurately Differentiate between Hypervirulent and Classical <named-content content-type="genus-species">Klebsiella pneumoniae</named-content>
title_full	The <named-content content-type="genus-species">Galleria mellonella</named-content> Infection Model Does Not Accurately Differentiate between Hypervirulent and Classical <named-content content-type="genus-species">Klebsiella pneumoniae</named-content>
title_fullStr	The <named-content content-type="genus-species">Galleria mellonella</named-content> Infection Model Does Not Accurately Differentiate between Hypervirulent and Classical <named-content content-type="genus-species">Klebsiella pneumoniae</named-content>
title_full_unstemmed	The <named-content content-type="genus-species">Galleria mellonella</named-content> Infection Model Does Not Accurately Differentiate between Hypervirulent and Classical <named-content content-type="genus-species">Klebsiella pneumoniae</named-content>
title_sort	<named-content content-type="genus-species">galleria mellonella</named-content> infection model does not accurately differentiate between hypervirulent and classical <named-content content-type="genus-species">klebsiella pneumoniae</named-content>
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/f5525bccdbaf46598571854b9c74de9e
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The <named-content content-type="genus-species">Galleria mellonella</named-content> Infection Model Does Not Accurately Differentiate between Hypervirulent and Classical <named-content content-type="genus-species">Klebsiella pneumoniae</named-content>

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