Indirect Pathogenicity of Haemophilus influenzae and Moraxella catarrhalis in Polymicrobial Otitis Media Occurs via Interspecies Quorum Signaling

Otitis media (OM) is among the leading diseases of childhood and is caused by opportunists that reside within the nasopharynx, such as and . As with most airway infections, it is now clear that OM infections involve multiple organisms. This study addresses the hypothesis that polymicrobial infection alters the course, severity, and/or treatability of OM disease. The results clearly show that coinfection with   and promotes the increased resistance of biofilms to antibiotics and host clearance. Using mutants with known biofilm defects, these phenotypes were shown to relate to biofilm maturation and autoinducer-2 (AI-2) quorum signaling. In support of the latter mechanism, chemically synthesized AI-2 (dihydroxypentanedione [DPD]) promoted increased biofilm formation and resistance to antibiotics. In the chinchilla infection model of OM, polymicrobial infection promoted persistence beyond the levels seen in animals infected with alone. Notably, no such enhancement of persistence was observed in animals infected with   and a quorum signaling-deficient mutant strain. We thus conclude that promotes persistence within polymicrobial biofilms via interspecies quorum signaling. AI-2 may therefore represent an ideal target for disruption of chronic polymicrobial infections. Moreover, these results strongly imply that successful vaccination against the unencapsulated strains that cause airway infections may also significantly impact chronic disease by removing a reservoir of the AI-2 signal that promotes persistence within biofilm. Otitis media (OM) is one of the most common childhood infections and is a leading reason for antibiotic prescriptions to children. Chronic and recurrent OM involves persistence of bacteria within biofilm communities, a state in which they are highly resistant to immune clearance and antibiotic treatment. While it is clear that most of these infections involve multiple species, the vast majority of knowledge about OM infections has been derived from work involving single bacterial species. There is a pressing need for better understanding of the impact of polymicrobial infection on the course, severity, and treatability of OM disease. In this study, we show that communication between bacterial species promotes bacterial persistence and resistance to antibiotics, which are important considerations in the diagnosis, prevention, and treatment of OM. Moreover, the results of this study indicate that successful preventive measures against could reduce the levels of disease caused by .

Duke Scholars

Author Kristin E.D. Weimer Pediatrics, Neonatology