A Serendipitous Mutation Reveals the Severe Virulence Defect of a <named-content content-type="genus-species">Klebsiella pneumonia</named-content>e <italic toggle="yes">fepB</italic> Mutant

ABSTRACT Klebsiella pneumoniae is considered a significant public health threat because of the emergence of multidrug-resistant strains and the challenge associated with treating life-threatening infections. Capsule, siderophores, and adhesins have been implicated as virulence determinants of K. pne...

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Autores principales:	Michelle Palacios, Christopher A. Broberg, Kimberly A. Walker, Virginia L. Miller
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	Klebsiella RamA enterobactin pneumonia siderophore yersiniabactin Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/14e5a52960df4e759eee08393712b382
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spelling	oai:doaj.org-article:14e5a52960df4e759eee08393712b3822021-11-15T15:22:04ZA Serendipitous Mutation Reveals the Severe Virulence Defect of a <named-content content-type="genus-species">Klebsiella pneumonia</named-content>e <italic toggle="yes">fepB</italic> Mutant10.1128/mSphere.00341-172379-5042https://doaj.org/article/14e5a52960df4e759eee08393712b3822017-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00341-17https://doaj.org/toc/2379-5042ABSTRACT Klebsiella pneumoniae is considered a significant public health threat because of the emergence of multidrug-resistant strains and the challenge associated with treating life-threatening infections. Capsule, siderophores, and adhesins have been implicated as virulence determinants of K. pneumoniae, yet we lack a clear understanding of how this pathogen causes disease. In a previous screen for virulence genes, we identified a potential new virulence locus and constructed a mutant (smr) with this locus deleted. In this study, we characterize the smr mutant and show that this mutation renders K. pneumoniae avirulent in a pneumonia model of infection. The smr mutant was expected to have a deletion of three genes, but subsequent genome sequencing indicated that a much larger deletion had occurred. Further analysis of the deleted region indicated that the virulence defect of the smr mutant could be attributed to the loss of FepB, a periplasmic protein required for import of the siderophore enterobactin. Interestingly, a ΔfepB mutant was more attenuated than a mutant unable to synthesize enterobactin, suggesting that additional processes are affected. As FepB is highly conserved among the members of the family Enterobacteriaceae, therapeutic targeting of FepB may be useful for the treatment of Klebsiella and other bacterial infections. IMPORTANCE In addition to having a reputation as the causative agent of several types of hospital-acquired infections, Klebsiella pneumoniae has gained widespread attention as a pathogen with a propensity for acquiring antibiotic resistance. It is capable of causing a range of infections, including urinary tract infections, pneumonia, and sepsis. Because of the rapid emergence of carbapenem resistance among Klebsiella strains, there is a dire need for a better understanding of virulence mechanisms and identification of new drug targets. Here, we identify the periplasmic transporter FepB as one such potential target.Michelle PalaciosChristopher A. BrobergKimberly A. WalkerVirginia L. MillerAmerican Society for MicrobiologyarticleKlebsiellaRamAenterobactinpneumoniasiderophoreyersiniabactinMicrobiologyQR1-502ENmSphere, Vol 2, Iss 4 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Klebsiella RamA enterobactin pneumonia siderophore yersiniabactin Microbiology QR1-502
spellingShingle	Klebsiella RamA enterobactin pneumonia siderophore yersiniabactin Microbiology QR1-502 Michelle Palacios Christopher A. Broberg Kimberly A. Walker Virginia L. Miller A Serendipitous Mutation Reveals the Severe Virulence Defect of a <named-content content-type="genus-species">Klebsiella pneumonia</named-content>e <italic toggle="yes">fepB</italic> Mutant
description	ABSTRACT Klebsiella pneumoniae is considered a significant public health threat because of the emergence of multidrug-resistant strains and the challenge associated with treating life-threatening infections. Capsule, siderophores, and adhesins have been implicated as virulence determinants of K. pneumoniae, yet we lack a clear understanding of how this pathogen causes disease. In a previous screen for virulence genes, we identified a potential new virulence locus and constructed a mutant (smr) with this locus deleted. In this study, we characterize the smr mutant and show that this mutation renders K. pneumoniae avirulent in a pneumonia model of infection. The smr mutant was expected to have a deletion of three genes, but subsequent genome sequencing indicated that a much larger deletion had occurred. Further analysis of the deleted region indicated that the virulence defect of the smr mutant could be attributed to the loss of FepB, a periplasmic protein required for import of the siderophore enterobactin. Interestingly, a ΔfepB mutant was more attenuated than a mutant unable to synthesize enterobactin, suggesting that additional processes are affected. As FepB is highly conserved among the members of the family Enterobacteriaceae, therapeutic targeting of FepB may be useful for the treatment of Klebsiella and other bacterial infections. IMPORTANCE In addition to having a reputation as the causative agent of several types of hospital-acquired infections, Klebsiella pneumoniae has gained widespread attention as a pathogen with a propensity for acquiring antibiotic resistance. It is capable of causing a range of infections, including urinary tract infections, pneumonia, and sepsis. Because of the rapid emergence of carbapenem resistance among Klebsiella strains, there is a dire need for a better understanding of virulence mechanisms and identification of new drug targets. Here, we identify the periplasmic transporter FepB as one such potential target.
format	article
author	Michelle Palacios Christopher A. Broberg Kimberly A. Walker Virginia L. Miller
author_facet	Michelle Palacios Christopher A. Broberg Kimberly A. Walker Virginia L. Miller
author_sort	Michelle Palacios
title	A Serendipitous Mutation Reveals the Severe Virulence Defect of a <named-content content-type="genus-species">Klebsiella pneumonia</named-content>e <italic toggle="yes">fepB</italic> Mutant
title_short	A Serendipitous Mutation Reveals the Severe Virulence Defect of a <named-content content-type="genus-species">Klebsiella pneumonia</named-content>e <italic toggle="yes">fepB</italic> Mutant
title_full	A Serendipitous Mutation Reveals the Severe Virulence Defect of a <named-content content-type="genus-species">Klebsiella pneumonia</named-content>e <italic toggle="yes">fepB</italic> Mutant
title_fullStr	A Serendipitous Mutation Reveals the Severe Virulence Defect of a <named-content content-type="genus-species">Klebsiella pneumonia</named-content>e <italic toggle="yes">fepB</italic> Mutant
title_full_unstemmed	A Serendipitous Mutation Reveals the Severe Virulence Defect of a <named-content content-type="genus-species">Klebsiella pneumonia</named-content>e <italic toggle="yes">fepB</italic> Mutant
title_sort	serendipitous mutation reveals the severe virulence defect of a <named-content content-type="genus-species">klebsiella pneumonia</named-content>e <italic toggle="yes">fepb</italic> mutant
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/14e5a52960df4e759eee08393712b382
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A Serendipitous Mutation Reveals the Severe Virulence Defect of a <named-content content-type="genus-species">Klebsiella pneumonia</named-content>e <italic toggle="yes">fepB</italic> Mutant

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