The Small Protein RmpD Drives Hypermucoviscosity in <named-content content-type="genus-species">Klebsiella pneumoniae</named-content>

ABSTRACT Klebsiella pneumoniae has a remarkable ability to cause a wide range of human diseases. It is divided into two broad classes: classical strains that are a notable problem in health care settings due to multidrug resistance, and hypervirulent (hv) strains that are historically drug sensitive...

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Autores principales:	Kimberly A. Walker, Logan P. Treat, Victoria E. Sepúlveda, Virginia L. Miller
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	RmpA RmpC hypervirulent HMV capsule hypermucoviscous Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/209942c105344f6e8186e47308c3054c
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spelling	oai:doaj.org-article:209942c105344f6e8186e47308c3054c2021-11-15T16:19:09ZThe Small Protein RmpD Drives Hypermucoviscosity in <named-content content-type="genus-species">Klebsiella pneumoniae</named-content>10.1128/mBio.01750-202150-7511https://doaj.org/article/209942c105344f6e8186e47308c3054c2020-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01750-20https://doaj.org/toc/2150-7511ABSTRACT Klebsiella pneumoniae has a remarkable ability to cause a wide range of human diseases. It is divided into two broad classes: classical strains that are a notable problem in health care settings due to multidrug resistance, and hypervirulent (hv) strains that are historically drug sensitive but able to establish disease in immunocompetent hosts. Alarmingly, there has been an increased frequency of clinical isolates that have both drug resistance and hv-associated genes. One such gene, rmpA, encodes a transcriptional regulator required for maximal capsule (cps) gene expression and confers hypermucoviscosity (HMV). This link has resulted in the assumption that HMV is caused by elevated capsule production. However, we recently reported a new cps regulator, RmpC, and ΔrmpC mutants have reduced cps expression but retain HMV, suggesting that capsule production and HMV may be separable traits. Here, we report the identification of a small protein, RmpD, that is essential for HMV but does not impact capsule. RmpD is 58 residues with a putative N-terminal transmembrane domain and highly positively charged C-terminal half, and it is conserved among other hv K. pneumoniae strains. Expression of rmpD in trans complements both ΔrmpD and ΔrmpA mutants for HMV, suggesting that RmpD is the key driver of this phenotype. The rmpD gene is located between rmpA and rmpC, within an operon regulated by RmpA. These data, combined with our previous work, suggest a model in which the RmpA-associated phenotypes are largely due to RmpA activating the expression of rmpD to produce HMV and rmpC to stimulate cps expression. IMPORTANCE Capsule is a critical virulence factor in Klebsiella pneumoniae, in both antibiotic-resistant classical strains and hypervirulent strains. Hypervirulent strains usually have a hypermucoviscosity (HMV) phenotype that contributes to their heightened virulence capacity, but the production of HMV is not understood. The transcriptional regulator RmpA is required for HMV and also activates capsule gene expression, leading to the assumption that HMV is caused by hyperproduction of capsule. We have identified a new gene (rmpD) required for HMV but not for capsule production. This distinction between HMV and capsule production will promote a better understanding of the mechanisms of hypervirulence, which is in great need given the alarming increase in clinical isolates with both drug resistance and hypervirulence traits.Kimberly A. WalkerLogan P. TreatVictoria E. SepúlvedaVirginia L. MillerAmerican Society for MicrobiologyarticleRmpARmpChypervirulentHMVcapsulehypermucoviscousMicrobiologyQR1-502ENmBio, Vol 11, Iss 5 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	RmpA RmpC hypervirulent HMV capsule hypermucoviscous Microbiology QR1-502
spellingShingle	RmpA RmpC hypervirulent HMV capsule hypermucoviscous Microbiology QR1-502 Kimberly A. Walker Logan P. Treat Victoria E. Sepúlveda Virginia L. Miller The Small Protein RmpD Drives Hypermucoviscosity in <named-content content-type="genus-species">Klebsiella pneumoniae</named-content>
description	ABSTRACT Klebsiella pneumoniae has a remarkable ability to cause a wide range of human diseases. It is divided into two broad classes: classical strains that are a notable problem in health care settings due to multidrug resistance, and hypervirulent (hv) strains that are historically drug sensitive but able to establish disease in immunocompetent hosts. Alarmingly, there has been an increased frequency of clinical isolates that have both drug resistance and hv-associated genes. One such gene, rmpA, encodes a transcriptional regulator required for maximal capsule (cps) gene expression and confers hypermucoviscosity (HMV). This link has resulted in the assumption that HMV is caused by elevated capsule production. However, we recently reported a new cps regulator, RmpC, and ΔrmpC mutants have reduced cps expression but retain HMV, suggesting that capsule production and HMV may be separable traits. Here, we report the identification of a small protein, RmpD, that is essential for HMV but does not impact capsule. RmpD is 58 residues with a putative N-terminal transmembrane domain and highly positively charged C-terminal half, and it is conserved among other hv K. pneumoniae strains. Expression of rmpD in trans complements both ΔrmpD and ΔrmpA mutants for HMV, suggesting that RmpD is the key driver of this phenotype. The rmpD gene is located between rmpA and rmpC, within an operon regulated by RmpA. These data, combined with our previous work, suggest a model in which the RmpA-associated phenotypes are largely due to RmpA activating the expression of rmpD to produce HMV and rmpC to stimulate cps expression. IMPORTANCE Capsule is a critical virulence factor in Klebsiella pneumoniae, in both antibiotic-resistant classical strains and hypervirulent strains. Hypervirulent strains usually have a hypermucoviscosity (HMV) phenotype that contributes to their heightened virulence capacity, but the production of HMV is not understood. The transcriptional regulator RmpA is required for HMV and also activates capsule gene expression, leading to the assumption that HMV is caused by hyperproduction of capsule. We have identified a new gene (rmpD) required for HMV but not for capsule production. This distinction between HMV and capsule production will promote a better understanding of the mechanisms of hypervirulence, which is in great need given the alarming increase in clinical isolates with both drug resistance and hypervirulence traits.
format	article
author	Kimberly A. Walker Logan P. Treat Victoria E. Sepúlveda Virginia L. Miller
author_facet	Kimberly A. Walker Logan P. Treat Victoria E. Sepúlveda Virginia L. Miller
author_sort	Kimberly A. Walker
title	The Small Protein RmpD Drives Hypermucoviscosity in <named-content content-type="genus-species">Klebsiella pneumoniae</named-content>
title_short	The Small Protein RmpD Drives Hypermucoviscosity in <named-content content-type="genus-species">Klebsiella pneumoniae</named-content>
title_full	The Small Protein RmpD Drives Hypermucoviscosity in <named-content content-type="genus-species">Klebsiella pneumoniae</named-content>
title_fullStr	The Small Protein RmpD Drives Hypermucoviscosity in <named-content content-type="genus-species">Klebsiella pneumoniae</named-content>
title_full_unstemmed	The Small Protein RmpD Drives Hypermucoviscosity in <named-content content-type="genus-species">Klebsiella pneumoniae</named-content>
title_sort	small protein rmpd drives hypermucoviscosity in <named-content content-type="genus-species">klebsiella pneumoniae</named-content>
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/209942c105344f6e8186e47308c3054c
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The Small Protein RmpD Drives Hypermucoviscosity in <named-content content-type="genus-species">Klebsiella pneumoniae</named-content>

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