Aggregative Adherence and Intestinal Colonization by Enteroaggregative <named-content content-type="genus-species">Escherichia coli</named-content> Are Produced by Interactions among Multiple Surface Factors

ABSTRACT Enteroaggregative Escherichia coli (EAEC) bacteria are exceptional colonizers that are associated with diarrhea. The genome of EAEC strain 042, a diarrheal pathogen validated in a human challenge study, encodes multiple colonization factors. Notable among them are aggregative adherence fimb...

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Autores principales:	Laura V. Blanton, Lawrence T. Wang, Jennifer Hofmann, Joshua DuBow, Alexander Lafrance, Stephen Kwak, Levi Bowers, Mandara A. Levine, Charles O. Hale, Philip M. Meneely, Iruka N. Okeke
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	enteroaggregative Escherichia coli adherence aggregative adherence fimbriae antiaggregative protein diarrhea diarrheagenic Escherichia coli Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/5da3cc9a95c0468db38d9c6a7553a514
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spelling	oai:doaj.org-article:5da3cc9a95c0468db38d9c6a7553a5142021-11-15T15:22:14ZAggregative Adherence and Intestinal Colonization by Enteroaggregative <named-content content-type="genus-species">Escherichia coli</named-content> Are Produced by Interactions among Multiple Surface Factors10.1128/mSphere.00078-182379-5042https://doaj.org/article/5da3cc9a95c0468db38d9c6a7553a5142018-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00078-18https://doaj.org/toc/2379-5042ABSTRACT Enteroaggregative Escherichia coli (EAEC) bacteria are exceptional colonizers that are associated with diarrhea. The genome of EAEC strain 042, a diarrheal pathogen validated in a human challenge study, encodes multiple colonization factors. Notable among them are aggregative adherence fimbriae (AAF/II) and a secreted antiaggregation protein (Aap). Deletion of aap is known to increase adherence, autoaggregation, and biofilm formation, so it was proposed that Aap counteracts AAF/II-mediated interactions. We hypothesized that Aap sterically masks heat-resistant agglutinin 1 (Hra1), an integral outer membrane protein recently identified as an accessory colonization factor. We propose that this masking accounts for reduced in vivo colonization upon hra1 deletion and yet no colonization-associated phenotypes when hra1 is deleted in vitro. Using single and double mutants of hra1, aap, and the AAF/II structural protein gene aafA, we demonstrated that increased adherence in aap mutants occurs even when AAF/II proteins are genetically or chemically removed. Deletion of hra1 together with aap abolishes the hyperadherence phenotype, demonstrating that Aap indeed masks Hra1. The presence of all three colonization factors, however, is necessary for optimal colonization and for rapidly building stacked-brick patterns on slides and cultured monolayers, the signature EAEC phenotype. Altogether, our data demonstrate that Aap serves to mask nonstructural adhesins such as Hra1 and that optimal colonization by EAEC is mediated through interactions among multiple surface factors. IMPORTANCE Enteroaggregative Escherichia coli (EAEC) bacteria are exceptional colonizers of the human intestine and can cause diarrhea. Compared to other E. coli pathogens, little is known about the genes and pathogenic mechanisms that differentiate EAEC from harmless commensal E. coli. EAEC bacteria attach via multiple proteins and structures, including long appendages produced by assembling molecules of AafA and a short surface protein called Hra1. EAEC also secretes an antiadherence protein (Aap; also known as dispersin) which remains loosely attached to the cell surface. This report shows that dispersin covers Hra1 such that the adhesive properties of EAEC seen in the laboratory are largely produced by AafA structures. When the bacteria colonize worms, dispersin is sloughed off, or otherwise removed, such that Hra1-mediated adherence occurs. All three factors are required for optimal colonization, as well as to produce the signature EAEC stacked-brick adherence pattern. Interplay among multiple colonization factors may be an essential feature of exceptional colonizers.Laura V. BlantonLawrence T. WangJennifer HofmannJoshua DuBowAlexander LafranceStephen KwakLevi BowersMandara A. LevineCharles O. HalePhilip M. MeneelyIruka N. OkekeAmerican Society for Microbiologyarticleenteroaggregative Escherichia coliadherenceaggregative adherence fimbriaeantiaggregative proteindiarrheadiarrheagenic Escherichia coliMicrobiologyQR1-502ENmSphere, Vol 3, Iss 2 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	enteroaggregative Escherichia coli adherence aggregative adherence fimbriae antiaggregative protein diarrhea diarrheagenic Escherichia coli Microbiology QR1-502
spellingShingle	enteroaggregative Escherichia coli adherence aggregative adherence fimbriae antiaggregative protein diarrhea diarrheagenic Escherichia coli Microbiology QR1-502 Laura V. Blanton Lawrence T. Wang Jennifer Hofmann Joshua DuBow Alexander Lafrance Stephen Kwak Levi Bowers Mandara A. Levine Charles O. Hale Philip M. Meneely Iruka N. Okeke Aggregative Adherence and Intestinal Colonization by Enteroaggregative <named-content content-type="genus-species">Escherichia coli</named-content> Are Produced by Interactions among Multiple Surface Factors
description	ABSTRACT Enteroaggregative Escherichia coli (EAEC) bacteria are exceptional colonizers that are associated with diarrhea. The genome of EAEC strain 042, a diarrheal pathogen validated in a human challenge study, encodes multiple colonization factors. Notable among them are aggregative adherence fimbriae (AAF/II) and a secreted antiaggregation protein (Aap). Deletion of aap is known to increase adherence, autoaggregation, and biofilm formation, so it was proposed that Aap counteracts AAF/II-mediated interactions. We hypothesized that Aap sterically masks heat-resistant agglutinin 1 (Hra1), an integral outer membrane protein recently identified as an accessory colonization factor. We propose that this masking accounts for reduced in vivo colonization upon hra1 deletion and yet no colonization-associated phenotypes when hra1 is deleted in vitro. Using single and double mutants of hra1, aap, and the AAF/II structural protein gene aafA, we demonstrated that increased adherence in aap mutants occurs even when AAF/II proteins are genetically or chemically removed. Deletion of hra1 together with aap abolishes the hyperadherence phenotype, demonstrating that Aap indeed masks Hra1. The presence of all three colonization factors, however, is necessary for optimal colonization and for rapidly building stacked-brick patterns on slides and cultured monolayers, the signature EAEC phenotype. Altogether, our data demonstrate that Aap serves to mask nonstructural adhesins such as Hra1 and that optimal colonization by EAEC is mediated through interactions among multiple surface factors. IMPORTANCE Enteroaggregative Escherichia coli (EAEC) bacteria are exceptional colonizers of the human intestine and can cause diarrhea. Compared to other E. coli pathogens, little is known about the genes and pathogenic mechanisms that differentiate EAEC from harmless commensal E. coli. EAEC bacteria attach via multiple proteins and structures, including long appendages produced by assembling molecules of AafA and a short surface protein called Hra1. EAEC also secretes an antiadherence protein (Aap; also known as dispersin) which remains loosely attached to the cell surface. This report shows that dispersin covers Hra1 such that the adhesive properties of EAEC seen in the laboratory are largely produced by AafA structures. When the bacteria colonize worms, dispersin is sloughed off, or otherwise removed, such that Hra1-mediated adherence occurs. All three factors are required for optimal colonization, as well as to produce the signature EAEC stacked-brick adherence pattern. Interplay among multiple colonization factors may be an essential feature of exceptional colonizers.
format	article
author	Laura V. Blanton Lawrence T. Wang Jennifer Hofmann Joshua DuBow Alexander Lafrance Stephen Kwak Levi Bowers Mandara A. Levine Charles O. Hale Philip M. Meneely Iruka N. Okeke
author_facet	Laura V. Blanton Lawrence T. Wang Jennifer Hofmann Joshua DuBow Alexander Lafrance Stephen Kwak Levi Bowers Mandara A. Levine Charles O. Hale Philip M. Meneely Iruka N. Okeke
author_sort	Laura V. Blanton
title	Aggregative Adherence and Intestinal Colonization by Enteroaggregative <named-content content-type="genus-species">Escherichia coli</named-content> Are Produced by Interactions among Multiple Surface Factors
title_short	Aggregative Adherence and Intestinal Colonization by Enteroaggregative <named-content content-type="genus-species">Escherichia coli</named-content> Are Produced by Interactions among Multiple Surface Factors
title_full	Aggregative Adherence and Intestinal Colonization by Enteroaggregative <named-content content-type="genus-species">Escherichia coli</named-content> Are Produced by Interactions among Multiple Surface Factors
title_fullStr	Aggregative Adherence and Intestinal Colonization by Enteroaggregative <named-content content-type="genus-species">Escherichia coli</named-content> Are Produced by Interactions among Multiple Surface Factors
title_full_unstemmed	Aggregative Adherence and Intestinal Colonization by Enteroaggregative <named-content content-type="genus-species">Escherichia coli</named-content> Are Produced by Interactions among Multiple Surface Factors
title_sort	aggregative adherence and intestinal colonization by enteroaggregative <named-content content-type="genus-species">escherichia coli</named-content> are produced by interactions among multiple surface factors
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/5da3cc9a95c0468db38d9c6a7553a514
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Aggregative Adherence and Intestinal Colonization by Enteroaggregative <named-content content-type="genus-species">Escherichia coli</named-content> Are Produced by Interactions among Multiple Surface Factors

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