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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| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2018-04-01
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| Series: | mSphere |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mSphere.00078-18 |
| _version_ | 1818927156787412992 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-20T03:08:32Z |
| format | Article |
| id | doaj.art-5da3cc9a95c0468db38d9c6a7553a514 |
| institution | Directory Open Access Journal |
| issn | 2379-5042 |
| language | English |
| last_indexed | 2024-12-20T03:08:32Z |
| publishDate | 2018-04-01 |
| publisher | American Society for Microbiology |
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| series | mSphere |
| spelling | doaj.art-5da3cc9a95c0468db38d9c6a7553a5142022-12-21T19:55:32ZengAmerican Society for MicrobiologymSphere2379-50422018-04-013210.1128/mSphere.00078-18Aggregative Adherence and Intestinal Colonization by Enteroaggregative <named-content content-type="genus-species">Escherichia coli</named-content> Are Produced by Interactions among Multiple Surface FactorsLaura V. Blanton0Lawrence T. Wang1Jennifer Hofmann2Joshua DuBow3Alexander Lafrance4Stephen Kwak5Levi Bowers6Mandara A. Levine7Charles O. Hale8Philip M. Meneely9Iruka N. Okeke10Department of Biology, Haverford College, Haverford, Pennsylvania, USADepartment of Biology, Haverford College, Haverford, Pennsylvania, USADepartment of Biology, Haverford College, Haverford, Pennsylvania, USADepartment of Biology, Haverford College, Haverford, Pennsylvania, USADepartment of Biology, Haverford College, Haverford, Pennsylvania, USADepartment of Biology, Haverford College, Haverford, Pennsylvania, USADepartment of Biology, Haverford College, Haverford, Pennsylvania, USADepartment of Biology, Haverford College, Haverford, Pennsylvania, USADepartment of Biology, Haverford College, Haverford, Pennsylvania, USADepartment of Biology, Haverford College, Haverford, Pennsylvania, USADepartment of Biology, Haverford College, Haverford, Pennsylvania, USAABSTRACT 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.https://journals.asm.org/doi/10.1128/mSphere.00078-18enteroaggregative Escherichia coliadherenceaggregative adherence fimbriaeantiaggregative proteindiarrheadiarrheagenic Escherichia coli |
| spellingShingle | 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 mSphere enteroaggregative Escherichia coli adherence aggregative adherence fimbriae antiaggregative protein diarrhea diarrheagenic Escherichia coli |
| 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_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_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_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 |
| topic | enteroaggregative Escherichia coli adherence aggregative adherence fimbriae antiaggregative protein diarrhea diarrheagenic Escherichia coli |
| url | https://journals.asm.org/doi/10.1128/mSphere.00078-18 |
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