Identification of biomarkers for differentiation of hypervirulent klebsiella pneumoniae from classical K. pneumoniae

Thomas A. Russo, Ruth Olson, Chi Tai Fang, Nicole Stoesser, Mark Miller, Ulrike MacDonald, Alan Hutson, Jason H. Barker, Ricardo M. La Hoz, James R. Johnson, Martin Backer, Rajinder Bajwa, Andrew T. Catanzaro, Derrick Crook, Kleper De Almeida, Joshua Fierer, David E. Greenberg, Michael Klevay, Payal Patel, Adam RatnerJin Town Wang, Jaroslaw Zola

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

A hypervirulent Klebsiella pneumoniae (hvKp) pathotype is undergoing global dissemination. In contrast to the usual health care-associated epidemiology of classical K. pneumoniae (cKp) infections, hvKp causes tissue-invasive infections in otherwise healthy individuals from the community, often involving multiple sites. An accurate test to identify hvKp strains is needed for improved patient care and epidemiologic studies. To fill this knowledge gap, clinical criteria or random blood isolates from North American and United Kingdom strain collections were used to assemble hvKp-rich (n 85) and cKp-rich (n 90) strain cohorts, respectively. The isolates were then assessed for multiple candidate biomarkers hypothesized to accurately differentiate the two cohorts. The genes peg-344, iroB, iucA, plasmid-borne rmpA gene (prmpA), and prmpA2 all demonstrated 0.95 diagnostic accuracy for identifying strains in the hvKp-rich cohort. Next, to validate this epidemiological analysis, all strains were assessed experimentally in a murine sepsis model. peg-344, iroB, iucA, prmpA, and prmpA2 were all associated with a hazard ratio of 25 for severe illness or death, additionally supporting their utility for identifying hvKp strains. Quantitative siderophore production of 30 g/ml also strongly predicted strains as members of the hvKp-rich cohort (accuracy, 0.96) and exhibited a hazard ratio of 31.7 for severe illness or death. The string test, a widely used marker for hvKp strains, performed less well, achieving an accuracy of only 0.90. Last, using the most accurate biomarkers to define hvKp, prevalence studies were performed on two Western strain collections. These data strongly support the utility of several laboratory markers for identifying hvKp strains with a high degree of accuracy.

Original languageEnglish (US)
Article numbere00776
JournalJournal of Clinical Microbiology
Volume56
Issue number9
DOIs
StatePublished - Sep 1 2018

Fingerprint

Klebsiella pneumoniae
Biomarkers
Plasmids
Klebsiella Infections
Genes
Siderophores
Epidemiologic Studies
Sepsis
Patient Care
Epidemiology
Cross-Sectional Studies
Delivery of Health Care

Keywords

  • Biomarkers
  • Classical Klebsiella pneumoniae
  • Diagnosis
  • Diagnostic test
  • Hypervirulent Klebsiella pneumoniae

ASJC Scopus subject areas

  • Microbiology (medical)

Cite this

Identification of biomarkers for differentiation of hypervirulent klebsiella pneumoniae from classical K. pneumoniae. / Russo, Thomas A.; Olson, Ruth; Fang, Chi Tai; Stoesser, Nicole; Miller, Mark; MacDonald, Ulrike; Hutson, Alan; Barker, Jason H.; La Hoz, Ricardo M.; Johnson, James R.; Backer, Martin; Bajwa, Rajinder; Catanzaro, Andrew T.; Crook, Derrick; De Almeida, Kleper; Fierer, Joshua; Greenberg, David E.; Klevay, Michael; Patel, Payal; Ratner, Adam; Wang, Jin Town; Zola, Jaroslaw.

In: Journal of Clinical Microbiology, Vol. 56, No. 9, e00776, 01.09.2018.

Research output: Contribution to journalArticle

Russo, TA, Olson, R, Fang, CT, Stoesser, N, Miller, M, MacDonald, U, Hutson, A, Barker, JH, La Hoz, RM, Johnson, JR, Backer, M, Bajwa, R, Catanzaro, AT, Crook, D, De Almeida, K, Fierer, J, Greenberg, DE, Klevay, M, Patel, P, Ratner, A, Wang, JT & Zola, J 2018, 'Identification of biomarkers for differentiation of hypervirulent klebsiella pneumoniae from classical K. pneumoniae', Journal of Clinical Microbiology, vol. 56, no. 9, e00776. https://doi.org/10.1128/JCM.00776-18
Russo, Thomas A. ; Olson, Ruth ; Fang, Chi Tai ; Stoesser, Nicole ; Miller, Mark ; MacDonald, Ulrike ; Hutson, Alan ; Barker, Jason H. ; La Hoz, Ricardo M. ; Johnson, James R. ; Backer, Martin ; Bajwa, Rajinder ; Catanzaro, Andrew T. ; Crook, Derrick ; De Almeida, Kleper ; Fierer, Joshua ; Greenberg, David E. ; Klevay, Michael ; Patel, Payal ; Ratner, Adam ; Wang, Jin Town ; Zola, Jaroslaw. / Identification of biomarkers for differentiation of hypervirulent klebsiella pneumoniae from classical K. pneumoniae. In: Journal of Clinical Microbiology. 2018 ; Vol. 56, No. 9.
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AU - Hutson, Alan

AU - Barker, Jason H.

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AU - Backer, Martin

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