Immunization with a Biofilm-Disrupting Nontypeable <italic toggle="yes">Haemophilus influenzae</italic> Vaccine Antigen Did Not Alter the Gut Microbiome in Chinchillas, Unlike Oral Delivery of a Broad-Spectrum Antibiotic Commonly Used for Otitis Media

ABSTRACT The use of broad-spectrum antibiotics to treat diseases, such as the highly prevalent pediatric disease otitis media (OM), contributes significantly to the worldwide emergence of multiple-antibiotic-resistant microbes, and gut dysbiosis with diarrhea is a common adverse sequela. Moreover, f...

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Autores principales:	Michael T. Bailey, Christian L. Lauber, Laura A. Novotny, Steven D. Goodman, Lauren O. Bakaletz
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	DNABII tip-chimer peptide dmLT otitis media microbiome Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/e70183c32d80473da1288610809dabc9
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spelling	oai:doaj.org-article:e70183c32d80473da1288610809dabc92021-11-15T15:29:16ZImmunization with a Biofilm-Disrupting Nontypeable <italic toggle="yes">Haemophilus influenzae</italic> Vaccine Antigen Did Not Alter the Gut Microbiome in Chinchillas, Unlike Oral Delivery of a Broad-Spectrum Antibiotic Commonly Used for Otitis Media10.1128/mSphere.00296-202379-5042https://doaj.org/article/e70183c32d80473da1288610809dabc92020-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00296-20https://doaj.org/toc/2379-5042ABSTRACT The use of broad-spectrum antibiotics to treat diseases, such as the highly prevalent pediatric disease otitis media (OM), contributes significantly to the worldwide emergence of multiple-antibiotic-resistant microbes, and gut dysbiosis with diarrhea is a common adverse sequela. Moreover, for many diseases, like OM, biofilms contribute significantly to chronicity and recurrence, yet biofilm-resident bacteria are characteristically highly resistant to antibiotics. The most cost-effective way to both prevent and resolve diseases like OM, as well as begin to address the problem of growing antibiotic resistance, would be via the development of novel approaches to eradicate bacterial biofilms. Toward this goal, we designed a vaccine antigen that induces the formation of antibodies that prevent biofilm formation and, thereby, experimental OM in the middle ears of chinchillas by the predominant Gram-negative pathogen responsible for this disease, nontypeable Haemophilus influenzae. These antibodies also significantly disrupt preexisting biofilms formed by diverse pathogens. Whereas preclinical data strongly support the continued development of this vaccine antigen, which targets an essential structural element of bacterial biofilms, a concern has been whether active immunization would also lead to unintended collateral damage in the form of an altered gut microbiome. To address this concern, we assessed changes in the microbiome of the chinchilla gut over time after the delivery of either amoxicillin-clavulanate, the standard of care for OM, or after immunization with our biofilm-targeted vaccine antigen either via a traditional subcutaneous route or via a novel noninvasive transcutaneous route. We show that differences in the abundance of specific taxa were found only in the stools of antibiotic-treated animals. IMPORTANCE The prevalence of chronic and recurrent diseases, combined with the overuse/abuse of antibiotics that has led to the sobering emergence of bacteria resistant to multiple antibiotics, has mandated that we develop novel approaches to better manage these diseases or, ideally, prevent them. Biofilms play a key role in the pathogenesis of chronic and recurrent bacterial diseases but are difficult, if not impossible, to eradicate with antibiotics. We developed a vaccine antigen designed to mediate biofilm disruption; however, it is also important that delivery of this vaccine does not induce collateral damage to the microbiome. The studies described here validated a vaccine approach that targets biofilms without the consequences of an altered gut microbiome. While delivery of the antibiotic most commonly given to children with ear infections did indeed alter the gut microbiome, as expected, immunization via traditional injection or by noninvasive delivery to the skin did not result in changes to the chinchilla gut microbiome.Michael T. BaileyChristian L. LauberLaura A. NovotnySteven D. GoodmanLauren O. BakaletzAmerican Society for MicrobiologyarticleDNABIItip-chimer peptidedmLTotitis mediamicrobiomeMicrobiologyQR1-502ENmSphere, Vol 5, Iss 2 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	DNABII tip-chimer peptide dmLT otitis media microbiome Microbiology QR1-502
spellingShingle	DNABII tip-chimer peptide dmLT otitis media microbiome Microbiology QR1-502 Michael T. Bailey Christian L. Lauber Laura A. Novotny Steven D. Goodman Lauren O. Bakaletz Immunization with a Biofilm-Disrupting Nontypeable <italic toggle="yes">Haemophilus influenzae</italic> Vaccine Antigen Did Not Alter the Gut Microbiome in Chinchillas, Unlike Oral Delivery of a Broad-Spectrum Antibiotic Commonly Used for Otitis Media
description	ABSTRACT The use of broad-spectrum antibiotics to treat diseases, such as the highly prevalent pediatric disease otitis media (OM), contributes significantly to the worldwide emergence of multiple-antibiotic-resistant microbes, and gut dysbiosis with diarrhea is a common adverse sequela. Moreover, for many diseases, like OM, biofilms contribute significantly to chronicity and recurrence, yet biofilm-resident bacteria are characteristically highly resistant to antibiotics. The most cost-effective way to both prevent and resolve diseases like OM, as well as begin to address the problem of growing antibiotic resistance, would be via the development of novel approaches to eradicate bacterial biofilms. Toward this goal, we designed a vaccine antigen that induces the formation of antibodies that prevent biofilm formation and, thereby, experimental OM in the middle ears of chinchillas by the predominant Gram-negative pathogen responsible for this disease, nontypeable Haemophilus influenzae. These antibodies also significantly disrupt preexisting biofilms formed by diverse pathogens. Whereas preclinical data strongly support the continued development of this vaccine antigen, which targets an essential structural element of bacterial biofilms, a concern has been whether active immunization would also lead to unintended collateral damage in the form of an altered gut microbiome. To address this concern, we assessed changes in the microbiome of the chinchilla gut over time after the delivery of either amoxicillin-clavulanate, the standard of care for OM, or after immunization with our biofilm-targeted vaccine antigen either via a traditional subcutaneous route or via a novel noninvasive transcutaneous route. We show that differences in the abundance of specific taxa were found only in the stools of antibiotic-treated animals. IMPORTANCE The prevalence of chronic and recurrent diseases, combined with the overuse/abuse of antibiotics that has led to the sobering emergence of bacteria resistant to multiple antibiotics, has mandated that we develop novel approaches to better manage these diseases or, ideally, prevent them. Biofilms play a key role in the pathogenesis of chronic and recurrent bacterial diseases but are difficult, if not impossible, to eradicate with antibiotics. We developed a vaccine antigen designed to mediate biofilm disruption; however, it is also important that delivery of this vaccine does not induce collateral damage to the microbiome. The studies described here validated a vaccine approach that targets biofilms without the consequences of an altered gut microbiome. While delivery of the antibiotic most commonly given to children with ear infections did indeed alter the gut microbiome, as expected, immunization via traditional injection or by noninvasive delivery to the skin did not result in changes to the chinchilla gut microbiome.
format	article
author	Michael T. Bailey Christian L. Lauber Laura A. Novotny Steven D. Goodman Lauren O. Bakaletz
author_facet	Michael T. Bailey Christian L. Lauber Laura A. Novotny Steven D. Goodman Lauren O. Bakaletz
author_sort	Michael T. Bailey
title	Immunization with a Biofilm-Disrupting Nontypeable <italic toggle="yes">Haemophilus influenzae</italic> Vaccine Antigen Did Not Alter the Gut Microbiome in Chinchillas, Unlike Oral Delivery of a Broad-Spectrum Antibiotic Commonly Used for Otitis Media
title_short	Immunization with a Biofilm-Disrupting Nontypeable <italic toggle="yes">Haemophilus influenzae</italic> Vaccine Antigen Did Not Alter the Gut Microbiome in Chinchillas, Unlike Oral Delivery of a Broad-Spectrum Antibiotic Commonly Used for Otitis Media
title_full	Immunization with a Biofilm-Disrupting Nontypeable <italic toggle="yes">Haemophilus influenzae</italic> Vaccine Antigen Did Not Alter the Gut Microbiome in Chinchillas, Unlike Oral Delivery of a Broad-Spectrum Antibiotic Commonly Used for Otitis Media
title_fullStr	Immunization with a Biofilm-Disrupting Nontypeable <italic toggle="yes">Haemophilus influenzae</italic> Vaccine Antigen Did Not Alter the Gut Microbiome in Chinchillas, Unlike Oral Delivery of a Broad-Spectrum Antibiotic Commonly Used for Otitis Media
title_full_unstemmed	Immunization with a Biofilm-Disrupting Nontypeable <italic toggle="yes">Haemophilus influenzae</italic> Vaccine Antigen Did Not Alter the Gut Microbiome in Chinchillas, Unlike Oral Delivery of a Broad-Spectrum Antibiotic Commonly Used for Otitis Media
title_sort	immunization with a biofilm-disrupting nontypeable <italic toggle="yes">haemophilus influenzae</italic> vaccine antigen did not alter the gut microbiome in chinchillas, unlike oral delivery of a broad-spectrum antibiotic commonly used for otitis media
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/e70183c32d80473da1288610809dabc9
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Immunization with a Biofilm-Disrupting Nontypeable <italic toggle="yes">Haemophilus influenzae</italic> Vaccine Antigen Did Not Alter the Gut Microbiome in Chinchillas, Unlike Oral Delivery of a Broad-Spectrum Antibiotic Commonly Used for Otitis Media

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