# Identification of new or unrecognized virulence genes in hypervirulent Klebsiella pneumoniae and antivirulence genes in classical K. pneumoniae.

> **NIH NIH R21** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2021 · $235,744

## Abstract

Project Summary/Abstract:
 A hypervirulent Klebsiella pneumoniae (hvKp) pathotype is undergoing global dissemination. In contrast to
the usual healthcare-associated epidemiology of classical K. pneumoniae (cKp) infections, hvKp causes tissue
invasive infections in otherwise healthy individuals from the community. Infection often involves multiple sites
that require source control (e.g. abscesses, necrotizing fasciitis) or locations that require site-specific therapy
(e.g. endophthalmitis, meningitis). Initial strains of hvKp were antimicrobial susceptible, however, recently hvKp
strains have been acquiring genes that encode extended-spectrum ß-lactamases and carbapenemases. The
reverse direction of transfer also can occur. Recently an extensively drug-resistant (XDR) cKp strain from
sequence type ST11 that had acquired part of a virulence plasmid present in hvKp was implicated as the
cause of a lethal outbreak in an intensive care unit. The prospect of a hypervirulent XDR pathogen is extremely
concerning.
 The goal of this proposal is to increase our limited understanding of the factors and generate initial insights
into the mechanisms responsible for hvKp’s hypervirulent phenotype. This, in turn, will enable logical strategies
to prevent or treat infections due to this true superbug. To accomplish this, we will utilize previously generated
in vivo virulence data developed with accurately defined cohorts of hvKp and cKp strains. These studies
identified four strain classes: 1- prototypical hvKp strains that possessed known virulence factors (VFs) and
were fully virulent in vivo; 2- hvKp strains that possessed known VFs but were less virulent than prototypical
hvKp strains in vivo; 3- prototypical cKp strains that did not possess known hvKp VFs and were significantly
less virulent in vivo compared to prototypical hvKp strains; and 4- cKp strains that did not possess known hvKp
VFs but were more virulent in vivo compared to prototypical cKp strains. These strain classes will be used as
“tools” to identify candidate genes that encode VFs or anti-VFs via genomic sequencing, sequence analysis
and delineation of gene sets, and subsequent appropriate comparisons (aim 1). Putative novel or
unrecognized VFs and anti-VFs will be prioritized, isogenic mutant and complemented derivatives will be
generated, and these constructs will be assessed in in vivo pneumonia and systemic infection models (aim 2).
The deliverables of this proposal will be the identification and in vivo validation of new or unrecognized VFs
and/or lack of anti-VFs that contribute to hvKp’s hypervirulent phenotype.

## Key facts

- **NIH application ID:** 10241918
- **Project number:** 5R21AI141826-02
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** THOMAS A RUSSO
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $235,744
- **Award type:** 5
- **Project period:** 2020-08-19 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10241918

## Citation

> US National Institutes of Health, RePORTER application 10241918, Identification of new or unrecognized virulence genes in hypervirulent Klebsiella pneumoniae and antivirulence genes in classical K. pneumoniae. (5R21AI141826-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10241918. Licensed CC0.

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