New Insight into Filamentous Hemagglutinin Secretion Reveals a Role for Full-Length FhaB in <italic toggle="yes">Bordetella</italic> Virulence

ABSTRACT Bordetella filamentous hemagglutinin (FHA), a primary component of acellular pertussis vaccines, contributes to virulence, but how it functions mechanistically is unclear. FHA is first synthesized as an ~370-kDa preproprotein called FhaB. Removal of an N-terminal signal peptide and a large...

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Autores principales:	Jeffrey A. Melvin, Erich V. Scheller, Christopher R. Noël, Peggy A. Cotter
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2015
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/abdb820fc385442cb40926f0005786cc
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spelling	oai:doaj.org-article:abdb820fc385442cb40926f0005786cc2021-11-15T15:41:27ZNew Insight into Filamentous Hemagglutinin Secretion Reveals a Role for Full-Length FhaB in <italic toggle="yes">Bordetella</italic> Virulence10.1128/mBio.01189-152150-7511https://doaj.org/article/abdb820fc385442cb40926f0005786cc2015-09-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01189-15https://doaj.org/toc/2150-7511ABSTRACT Bordetella filamentous hemagglutinin (FHA), a primary component of acellular pertussis vaccines, contributes to virulence, but how it functions mechanistically is unclear. FHA is first synthesized as an ~370-kDa preproprotein called FhaB. Removal of an N-terminal signal peptide and a large C-terminal prodomain (PD) during secretion results in “mature” ~250-kDa FHA, which has been assumed to be the biologically active form of the protein. Deletion of two C-terminal subdomains of FhaB did not affect production of functional FHA, and the mutant strains were indistinguishable from wild-type bacteria for their ability to adhere to the lower respiratory tract and to suppress inflammation in the lungs of mice. However, the mutant strains, which produced altered FhaB molecules, were eliminated from the lower respiratory tract much faster than wild-type B. bronchiseptica, suggesting a defect in resistance to early immune-mediated clearance. Our results revealed, unexpectedly, that full-length FhaB plays a critical role in B. bronchiseptica persistence in the lower respiratory tract. IMPORTANCE The Bordetella filamentous hemagglutinin (FHA) is a primary component of the acellular pertussis vaccine and an important virulence factor. FHA is initially produced as a large protein that is processed during secretion to the bacterial surface. As with most processed proteins, the mature form of FHA has been assumed to be the functional form of the protein. However, our results indicate that the full-length form plays an essential role in virulence in vivo. Furthermore, we have found that FHA contains intramolecular regulators of processing and that this control of processing is integral to its virulence activities. This report highlights the advantage of studying protein maturation and function simultaneously, as a role for the full-length form of FHA was evident only from in vivo infection studies and not from in vitro studies on the production or maturation of FHA or even from in vitro virulence-associated activity assays.Jeffrey A. MelvinErich V. SchellerChristopher R. NoëlPeggy A. CotterAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 6, Iss 4 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Jeffrey A. Melvin Erich V. Scheller Christopher R. Noël Peggy A. Cotter New Insight into Filamentous Hemagglutinin Secretion Reveals a Role for Full-Length FhaB in <italic toggle="yes">Bordetella</italic> Virulence
description	ABSTRACT Bordetella filamentous hemagglutinin (FHA), a primary component of acellular pertussis vaccines, contributes to virulence, but how it functions mechanistically is unclear. FHA is first synthesized as an ~370-kDa preproprotein called FhaB. Removal of an N-terminal signal peptide and a large C-terminal prodomain (PD) during secretion results in “mature” ~250-kDa FHA, which has been assumed to be the biologically active form of the protein. Deletion of two C-terminal subdomains of FhaB did not affect production of functional FHA, and the mutant strains were indistinguishable from wild-type bacteria for their ability to adhere to the lower respiratory tract and to suppress inflammation in the lungs of mice. However, the mutant strains, which produced altered FhaB molecules, were eliminated from the lower respiratory tract much faster than wild-type B. bronchiseptica, suggesting a defect in resistance to early immune-mediated clearance. Our results revealed, unexpectedly, that full-length FhaB plays a critical role in B. bronchiseptica persistence in the lower respiratory tract. IMPORTANCE The Bordetella filamentous hemagglutinin (FHA) is a primary component of the acellular pertussis vaccine and an important virulence factor. FHA is initially produced as a large protein that is processed during secretion to the bacterial surface. As with most processed proteins, the mature form of FHA has been assumed to be the functional form of the protein. However, our results indicate that the full-length form plays an essential role in virulence in vivo. Furthermore, we have found that FHA contains intramolecular regulators of processing and that this control of processing is integral to its virulence activities. This report highlights the advantage of studying protein maturation and function simultaneously, as a role for the full-length form of FHA was evident only from in vivo infection studies and not from in vitro studies on the production or maturation of FHA or even from in vitro virulence-associated activity assays.
format	article
author	Jeffrey A. Melvin Erich V. Scheller Christopher R. Noël Peggy A. Cotter
author_facet	Jeffrey A. Melvin Erich V. Scheller Christopher R. Noël Peggy A. Cotter
author_sort	Jeffrey A. Melvin
title	New Insight into Filamentous Hemagglutinin Secretion Reveals a Role for Full-Length FhaB in <italic toggle="yes">Bordetella</italic> Virulence
title_short	New Insight into Filamentous Hemagglutinin Secretion Reveals a Role for Full-Length FhaB in <italic toggle="yes">Bordetella</italic> Virulence
title_full	New Insight into Filamentous Hemagglutinin Secretion Reveals a Role for Full-Length FhaB in <italic toggle="yes">Bordetella</italic> Virulence
title_fullStr	New Insight into Filamentous Hemagglutinin Secretion Reveals a Role for Full-Length FhaB in <italic toggle="yes">Bordetella</italic> Virulence
title_full_unstemmed	New Insight into Filamentous Hemagglutinin Secretion Reveals a Role for Full-Length FhaB in <italic toggle="yes">Bordetella</italic> Virulence
title_sort	new insight into filamentous hemagglutinin secretion reveals a role for full-length fhab in <italic toggle="yes">bordetella</italic> virulence
publisher	American Society for Microbiology
publishDate	2015
url	https://doaj.org/article/abdb820fc385442cb40926f0005786cc
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New Insight into Filamentous Hemagglutinin Secretion Reveals a Role for Full-Length FhaB in <italic toggle="yes">Bordetella</italic> Virulence

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