# Understanding hypermucoviscosity in Klebsiella

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $482,562

## Abstract

Abstract
 Klebsiella pneumoniae (Kpn) is a leading cause of Gram-negative nosocomial infections and is associated
with a high mortality rate. Antibiotic resistance is a growing issue among the Enterobacteriaceae and of the
Enterobacteriaceae Kpn is the most prevalent extended spectrum β-lactamase and carbapenem resistant
Enterobacteriaceae isolate. The increasing prevalence of antibiotic-resistant Kpn only serves to compound its
clinical importance and to complicate treatment options. Capsule has been established as a key virulence
factor and is this species best studied virulence factor. Kpn strains are broadly classified as hypervirulent (hv)
or classical, with hv strains typically causing community acquired liver abscess and invasive infections.
Classical strains are more typically associated with nosocomial infections. The hv strains have a
hypermucoviscous (HMV) phenotype thought to be due to over-production of capsule and have acquired rmpA
that contributes to increased capsule (cps) gene expression. Most classical strains, including recent clinical
isolates associated with carbapenem resistance (ST258) are not HMV, do not have the rmpA gene and are not
virulent in mouse models of infection. Recent reports of these multidrug resistant strains acquiring the
HMV phenotype is of significant concern and amplifies the need to understand what HMV is, how it is
produced and how it contributes to virulence. Despite the apparent association between HMV and
over-production of capsule, what causes the HMV phenotype and its relationship to capsule
production is not known. Recent work from our lab using the HMV strain KPPR1S has shown that deletion of
rmpA causes decreases in expression from cps promoters, and reduction (but not complete loss) in both
capsule production and HMV. In addition, we found that rmpA is the first gene of an operon (rmpADC) and
that RmpA positively regulates expression of the operon. Results from analysis of a complete deletion of the
operon with the individual genes indicates that from this locus, RmpA primarily is required for expression of the
operon, that only RmpC is necessary for expression of cps genes, and that only RmpD is necessary for HMV.
Consistent with this, a mutant lacking only rmpD retains WT levels of cps gene expression, capsule production
and is HMV negative. The rmpD mutant is the first mutant identified that separates HMV from the over-
production of capsule, and the phenotype of the strain only expressing rmpC indicates that over-
production of capsule alone is not sufficient for HMV. Due to the importance of HMV to the virulence of hv
Kpn strains, the potential for classical strains to acquire HMV, the incomplete picture of what constitutes HMV
and what is required to produce HMV, we propose to a) gain a better understanding of RmpD, (b) characterize
the interacting partners of RmpD and how they affect HMV, and determine the composition of the HMV
exopolysaccharide, and (c) examine how HMV contributes to...

## Key facts

- **NIH application ID:** 10050316
- **Project number:** 1R01AI148197-01A1
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** VIRGINIA L MILLER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $482,562
- **Award type:** 1
- **Project period:** 2020-07-16 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10050316

## Citation

> US National Institutes of Health, RePORTER application 10050316, Understanding hypermucoviscosity in Klebsiella (1R01AI148197-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10050316. Licensed CC0.

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