Antibodies against the Majority Subunit (PilA) of the Type IV Pilus of Nontypeable Haemophilus influenzae Disperse Moraxella catarrhalis from a Dual-Species Biofilm

Abstract

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.

Moraxella catarrhalis Promotes Stable Polymicrobial Biofilms With the Major Otopathogens

“…We were also able to confirm that M. catarrhalis and NTHi successfully co-colonize in dual species biofilms as previously reported . Additionally, in our dual species model M. catarrhalis is able to promote the biofilm formation of NTHi supporting recently published work by Mokrzan et al (2018). These observations have important implications because prolonged nasopharyngeal carriage subsequently increases the potential for transition to disease.…”

“…Biofilm formation was quantified over time via CFU enumeration. Figure 1A, shows that NTHi forms a slightly more robust biofilm, ∼1 log greater, in dual species biofilms with M. catarrhalis than in monomicrobial biofilms which is consistent with previously reported data (Mokrzan et al, 2018). This is a statistically significant increase in viable NTHi at 48 h as compared to NTHi grown in monomicrobial biofilms (Supplementary Figure S1A).…”

Panel 7 – Pathogenesis of otitis media – a review of the literature between 2015 and 2019

“…H. influenzae often co-exists with other otopathogens, such as S. pneumoniae, M. catarrhalis and A. otitidis [86,88,97,120], and these organisms are often found together in polymicrobial biofilms [119,121]. Otopathogens combining into dual or multispecies biofilms are often at an advantage due to interspecies signaling and the ability of one organism to protect the other from antimicrobial factors [122,123]. These mechanisms of persistence and disease chronicity are important to understand both from the perspective of disease pathogenesis and to develop treatments and preventative strategies.…”

“…Little work has been done recently on treatment and prevention of polymicrobial biofilms; however, new treatments/vaccines developed against important NTHi proteins have also been demonstrated to be effective in preventing and treating multispecies biofilms with both bacteria and viruses [123,127]. These represent important areas of research that need to be extended.…”

Otitis media pathogens – A life entrapped in biofilm communities

“…Treatment of multispecies biofilms has been reported using antioxidant compounds, particularly Nacetyl-L-cysteine and cysteamine (Domenech and Garc ıa 2016), esters of bicyclic amines (Roig-Molina et al 2019), and also antibodies against TFP of NTHi prevented and disrupted multispecies biofilms via an interspecies quorum signal at temperatures that mimic the nasopharynx (34 C) or the ME (37 C) (Mokrzan et al 2018).…”