Identification of Pathogenicity-Associated Loci in <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> from Hospitalized Patients

ABSTRACT Despite insights gained through experimental models, the set of bacterial genes important for human infection is unclear for many of our most threatening pathogens. Klebsiella pneumoniae is a leading cause of health care-associated infections (HAIs) and commonly colonizes hospitalized patie...

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Autores principales: Rebekah M. Martin, Jie Cao, Weisheng Wu, Lili Zhao, David M. Manthei, Ali Pirani, Evan Snitkin, Preeti N. Malani, Krishna Rao, Michael A. Bachman
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Publicado: American Society for Microbiology 2018
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spelling oai:doaj.org-article:40a29fbd0ddd46af832ba1d1635f47562021-12-02T18:15:44ZIdentification of Pathogenicity-Associated Loci in <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> from Hospitalized Patients10.1128/mSystems.00015-182379-5077https://doaj.org/article/40a29fbd0ddd46af832ba1d1635f47562018-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00015-18https://doaj.org/toc/2379-5077ABSTRACT Despite insights gained through experimental models, the set of bacterial genes important for human infection is unclear for many of our most threatening pathogens. Klebsiella pneumoniae is a leading cause of health care-associated infections (HAIs) and commonly colonizes hospitalized patients, but the factors that determine whether a particular isolate causes disease or remains a colonizer are poorly understood. To identify bacterial genes associated with K. pneumoniae infection, a case-control study was performed comparing infected and asymptomatic colonized patients. Comparative bacterial genomics was combined with a conditional logit model that identified patient factors differentiating cases from controls. This method identified five gene loci associated with infection after adjustment for patient factors, including a psicose sugar utilization locus that was validated as a fitness factor during mouse lung infection. These results indicate that bacterial genome-wide association studies of patients can identify loci associated with HAIs and important in infection models. IMPORTANCE Klebsiella pneumoniae is a common cause of infections in the health care setting. This work supports a paradigm for K. pneumoniae pathogenesis where the accessory genome, composed of genes present in some but not all isolates, influences whether a strain causes infection or asymptomatic colonization, after accounting for patient-level factors. Identification of patients at high risk of infection could allow interventions to prevent or rapidly treat K. pneumoniae infections. Author Video: An author video summary of this article is available.Rebekah M. MartinJie CaoWeisheng WuLili ZhaoDavid M. MantheiAli PiraniEvan SnitkinPreeti N. MalaniKrishna RaoMichael A. BachmanAmerican Society for MicrobiologyarticleKlebsiellacomparative genomicsintestinal colonizationpathogenesispsicosetelluriteMicrobiologyQR1-502ENmSystems, Vol 3, Iss 3 (2018)
institution DOAJ
collection DOAJ
language EN
topic Klebsiella
comparative genomics
intestinal colonization
pathogenesis
psicose
tellurite
Microbiology
QR1-502
spellingShingle Klebsiella
comparative genomics
intestinal colonization
pathogenesis
psicose
tellurite
Microbiology
QR1-502
Rebekah M. Martin
Jie Cao
Weisheng Wu
Lili Zhao
David M. Manthei
Ali Pirani
Evan Snitkin
Preeti N. Malani
Krishna Rao
Michael A. Bachman
Identification of Pathogenicity-Associated Loci in <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> from Hospitalized Patients
description ABSTRACT Despite insights gained through experimental models, the set of bacterial genes important for human infection is unclear for many of our most threatening pathogens. Klebsiella pneumoniae is a leading cause of health care-associated infections (HAIs) and commonly colonizes hospitalized patients, but the factors that determine whether a particular isolate causes disease or remains a colonizer are poorly understood. To identify bacterial genes associated with K. pneumoniae infection, a case-control study was performed comparing infected and asymptomatic colonized patients. Comparative bacterial genomics was combined with a conditional logit model that identified patient factors differentiating cases from controls. This method identified five gene loci associated with infection after adjustment for patient factors, including a psicose sugar utilization locus that was validated as a fitness factor during mouse lung infection. These results indicate that bacterial genome-wide association studies of patients can identify loci associated with HAIs and important in infection models. IMPORTANCE Klebsiella pneumoniae is a common cause of infections in the health care setting. This work supports a paradigm for K. pneumoniae pathogenesis where the accessory genome, composed of genes present in some but not all isolates, influences whether a strain causes infection or asymptomatic colonization, after accounting for patient-level factors. Identification of patients at high risk of infection could allow interventions to prevent or rapidly treat K. pneumoniae infections. Author Video: An author video summary of this article is available.
format article
author Rebekah M. Martin
Jie Cao
Weisheng Wu
Lili Zhao
David M. Manthei
Ali Pirani
Evan Snitkin
Preeti N. Malani
Krishna Rao
Michael A. Bachman
author_facet Rebekah M. Martin
Jie Cao
Weisheng Wu
Lili Zhao
David M. Manthei
Ali Pirani
Evan Snitkin
Preeti N. Malani
Krishna Rao
Michael A. Bachman
author_sort Rebekah M. Martin
title Identification of Pathogenicity-Associated Loci in <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> from Hospitalized Patients
title_short Identification of Pathogenicity-Associated Loci in <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> from Hospitalized Patients
title_full Identification of Pathogenicity-Associated Loci in <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> from Hospitalized Patients
title_fullStr Identification of Pathogenicity-Associated Loci in <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> from Hospitalized Patients
title_full_unstemmed Identification of Pathogenicity-Associated Loci in <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> from Hospitalized Patients
title_sort identification of pathogenicity-associated loci in <named-content content-type="genus-species">klebsiella pneumoniae</named-content> from hospitalized patients
publisher American Society for Microbiology
publishDate 2018
url https://doaj.org/article/40a29fbd0ddd46af832ba1d1635f4756
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