Antibodies against the Majority Subunit (PilA) of the Type IV Pilus of Nontypeable Haemophilus influenzae Disperse Moraxella catarrhalis from a Dual-Species Biofilm. mBio 2018 Dec 11;9(6)
Date
12/13/2018Pubmed ID
30538189Pubmed Central ID
PMC6299487DOI
10.1128/mBio.02423-18Scopus ID
2-s2.0-85058590472 (requires institutional sign-in at Scopus site) 29 CitationsAbstract
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.
Author List
Mokrzan EM, Novotny LA, Brockman KL, Bakaletz LOAuthor
Kenneth Brockman PhD Assistant Professor in the Microbiology and Immunology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Antibodies, BacterialBiofilms
Fimbriae Proteins
Fimbriae, Bacterial
Haemophilus influenzae
Humans
