Antibodies against the Majority Subunit (PilA) of the Type IV Pilus of Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content> Disperse <named-content content-type="genus-species">Moraxella catarrhalis</named-content> from a Dual-Species Biofilm

ABSTRACT Otitis media (OM) is often polymicrobial, with nontypeable Haemophilus influenzae (NTHI) and Moraxella catarrhalis (Mcat) frequently cocultured from clinical specimens. Bacterial biofilms in the middle ear contribute to the chronicity and recurrence of OM; therefore, strategies to disrupt b...

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Autores principales:	Elaine M. Mokrzan, Laura A. Novotny, Kenneth L. Brockman, Lauren O. Bakaletz
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	LuxS OMP P5 otitis media quorum sensing vaccine Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/6f786e962b5a49f2955a55512c060fa9
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spelling	oai:doaj.org-article:6f786e962b5a49f2955a55512c060fa92021-11-15T15:52:19ZAntibodies against the Majority Subunit (PilA) of the Type IV Pilus of Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content> Disperse <named-content content-type="genus-species">Moraxella catarrhalis</named-content> from a Dual-Species Biofilm10.1128/mBio.02423-182150-7511https://doaj.org/article/6f786e962b5a49f2955a55512c060fa92018-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02423-18https://doaj.org/toc/2150-7511ABSTRACT Otitis media (OM) is often polymicrobial, with nontypeable Haemophilus influenzae (NTHI) and Moraxella catarrhalis (Mcat) frequently cocultured from clinical specimens. Bacterial biofilms in the middle ear contribute to the chronicity and recurrence of OM; therefore, strategies to disrupt biofilms are needed. We have focused our vaccine development efforts on the majority subunit of NTHI type IV pili, PilA. Antibodies against a recombinant, soluble form of PilA (rsPilA) both disrupt and prevent the formation of NTHI biofilms in vitro. Moreover, immunization with rsPilA prevents and resolves NTHI-induced experimental OM. Here, we show that antibodies against rsPilA also prevent and disrupt polymicrobial biofilms. Dual-species biofilms formed by NTHI and Mcat at temperatures that mimic the human nasopharynx (34°C) or middle ear (37°C) were exposed to antiserum against either rsPilA or the OMP P5 adhesin of NTHI. NTHI+Mcat biofilm formation was significantly inhibited by antiserum directed against both adhesin proteins at either temperature. However, only anti-rsPilA disrupted NTHI+Mcat preestablished biofilms at either temperature and actively dispersed both NTHI and Mcat via interspecies quorum signaling. Newly released NTHI and Mcat were significantly more susceptible to killing by antibiotics. Taken together, these results revealed new opportunities for treatment of biofilm-associated diseases via a strategy that combines vaccine-induced antibody-mediated biofilm dispersal with traditional antibiotics, at a significantly reduced dosage to exploit the newly released, antibiotic-sensitive phenotype. Combined, our data strongly support the utility of rsPilA both as a preventative and as a therapeutic vaccine antigen for polymicrobial OM due to NTHI and Mcat. IMPORTANCE Middle ear infections (or otitis media [OM]) are highly prevalent among children worldwide and present a tremendous socioeconomic challenge for health care systems. More importantly, this disease diminishes the quality of life of young children. OM is often chronic and recurrent, due to the presence of highly antibiotic-resistant communities of bacteria (called biofilms) that persist within the middle ear space. To combat these recalcitrant infections, new and powerful biofilm-directed approaches are needed. Here, we describe the ability to disrupt a biofilm formed by the two most common bacteria that cause chronic and recurrent OM in children, via an approach that combines the power of vaccines with that of traditional antibiotics. An outcome of this strategy is that antibiotics can more easily kill the bacteria that our vaccine-induced antibodies have released from the biofilm. We believe that this approach holds great promise for both the prevention and treatment of OM.Elaine M. MokrzanLaura A. NovotnyKenneth L. BrockmanLauren O. BakaletzAmerican Society for MicrobiologyarticleLuxSOMP P5otitis mediaquorum sensingvaccineMicrobiologyQR1-502ENmBio, Vol 9, Iss 6 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	LuxS OMP P5 otitis media quorum sensing vaccine Microbiology QR1-502
spellingShingle	LuxS OMP P5 otitis media quorum sensing vaccine Microbiology QR1-502 Elaine M. Mokrzan Laura A. Novotny Kenneth L. Brockman Lauren O. Bakaletz Antibodies against the Majority Subunit (PilA) of the Type IV Pilus of Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content> Disperse <named-content content-type="genus-species">Moraxella catarrhalis</named-content> from a Dual-Species Biofilm
description	ABSTRACT Otitis media (OM) is often polymicrobial, with nontypeable Haemophilus influenzae (NTHI) and Moraxella catarrhalis (Mcat) frequently cocultured from clinical specimens. Bacterial biofilms in the middle ear contribute to the chronicity and recurrence of OM; therefore, strategies to disrupt biofilms are needed. We have focused our vaccine development efforts on the majority subunit of NTHI type IV pili, PilA. Antibodies against a recombinant, soluble form of PilA (rsPilA) both disrupt and prevent the formation of NTHI biofilms in vitro. Moreover, immunization with rsPilA prevents and resolves NTHI-induced experimental OM. Here, we show that antibodies against rsPilA also prevent and disrupt polymicrobial biofilms. Dual-species biofilms formed by NTHI and Mcat at temperatures that mimic the human nasopharynx (34°C) or middle ear (37°C) were exposed to antiserum against either rsPilA or the OMP P5 adhesin of NTHI. NTHI+Mcat biofilm formation was significantly inhibited by antiserum directed against both adhesin proteins at either temperature. However, only anti-rsPilA disrupted NTHI+Mcat preestablished biofilms at either temperature and actively dispersed both NTHI and Mcat via interspecies quorum signaling. Newly released NTHI and Mcat were significantly more susceptible to killing by antibiotics. Taken together, these results revealed new opportunities for treatment of biofilm-associated diseases via a strategy that combines vaccine-induced antibody-mediated biofilm dispersal with traditional antibiotics, at a significantly reduced dosage to exploit the newly released, antibiotic-sensitive phenotype. Combined, our data strongly support the utility of rsPilA both as a preventative and as a therapeutic vaccine antigen for polymicrobial OM due to NTHI and Mcat. IMPORTANCE Middle ear infections (or otitis media [OM]) are highly prevalent among children worldwide and present a tremendous socioeconomic challenge for health care systems. More importantly, this disease diminishes the quality of life of young children. OM is often chronic and recurrent, due to the presence of highly antibiotic-resistant communities of bacteria (called biofilms) that persist within the middle ear space. To combat these recalcitrant infections, new and powerful biofilm-directed approaches are needed. Here, we describe the ability to disrupt a biofilm formed by the two most common bacteria that cause chronic and recurrent OM in children, via an approach that combines the power of vaccines with that of traditional antibiotics. An outcome of this strategy is that antibiotics can more easily kill the bacteria that our vaccine-induced antibodies have released from the biofilm. We believe that this approach holds great promise for both the prevention and treatment of OM.
format	article
author	Elaine M. Mokrzan Laura A. Novotny Kenneth L. Brockman Lauren O. Bakaletz
author_facet	Elaine M. Mokrzan Laura A. Novotny Kenneth L. Brockman Lauren O. Bakaletz
author_sort	Elaine M. Mokrzan
title	Antibodies against the Majority Subunit (PilA) of the Type IV Pilus of Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content> Disperse <named-content content-type="genus-species">Moraxella catarrhalis</named-content> from a Dual-Species Biofilm
title_short	Antibodies against the Majority Subunit (PilA) of the Type IV Pilus of Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content> Disperse <named-content content-type="genus-species">Moraxella catarrhalis</named-content> from a Dual-Species Biofilm
title_full	Antibodies against the Majority Subunit (PilA) of the Type IV Pilus of Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content> Disperse <named-content content-type="genus-species">Moraxella catarrhalis</named-content> from a Dual-Species Biofilm
title_fullStr	Antibodies against the Majority Subunit (PilA) of the Type IV Pilus of Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content> Disperse <named-content content-type="genus-species">Moraxella catarrhalis</named-content> from a Dual-Species Biofilm
title_full_unstemmed	Antibodies against the Majority Subunit (PilA) of the Type IV Pilus of Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content> Disperse <named-content content-type="genus-species">Moraxella catarrhalis</named-content> from a Dual-Species Biofilm
title_sort	antibodies against the majority subunit (pila) of the type iv pilus of nontypeable <named-content content-type="genus-species">haemophilus influenzae</named-content> disperse <named-content content-type="genus-species">moraxella catarrhalis</named-content> from a dual-species biofilm
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/6f786e962b5a49f2955a55512c060fa9
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Antibodies against the Majority Subunit (PilA) of the Type IV Pilus of Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content> Disperse <named-content content-type="genus-species">Moraxella catarrhalis</named-content> from a Dual-Species Biofilm

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