Ear infections: almost every kid has suffered through them at least once, making otitis media the most common reason for pediatric visits and new antibiotic prescriptions in children. But those little bottles of sweet pink antibiotics don’t always clear up ear infections. Bacteria often form mixed-species biofilms inside the ear, which afford the bacteria some protection from chemical onslaughts. A new paper just released by mBio reveals another reason these chronic biofilm infections are so recalcitrant: the bacteria may be cheering one another on.
Armbruster et al. looked at two species that often co-occur in ear infections, Haemophilus influenzae and Moraxella catarrhalis, to determine whether infection with multiple species has an effect on severity and treatability. They showed that when M. catarrhalis and H. influenzae are grown on a glass slide together, M. catarrhalis made beta-lactamases that deactivate the ampicillin and protected itself AND H. influenzae from ampicillin.
But the more surprising results came out when they looked at the effect of biofilm defect mutations on persistence. Wild type H. influenzae afforded better protection to M. catarrhalis than the strains with biofilm defect mutations did, but these mutant phenotypes relate not only to biofilm maturation - they also effect autoinducer-2 (AI-2) quorum signaling. The effected gene, luxS, is the genetic determinant for the production of AI-2, commonly referred to as an interspecies signal. Recent evidence suggests that bacterial species that don’t make AI-2, like M. catarrhalis, may still sense and respond to the AI-2 signal.
To test whether M. catarrhalis was listening in on AI-2 signals, they spiked cultures of the bacterium with a synthesized precursor of the autoinducer, then tracked the degradation of the compound over time. M. catarrhalis depleted the compound, formed thick, robust biofilms that were inherently more resistant to clarithromycin than non-spiked cultures. Follow-up work in chinchilla ears revealed that co-infection with the two strains enabled M. catarrhalis to thrive. (Who knew chinchillas were a good model for ear infections? I didn’t.)
“That’s an important finding – this is the first description of cosignalling in this environment,” says Larry McDaniel, a member of mBio’s Board of Editors and a professor at the University of Mississippi Medical Center. “AI-2 is able to activate or signal to M. catarrhalis, which allows it to persist in the ear. Without that signal, it’s likely that M. catarrhalis would be cleared,” says McDaniel. The bacteria help one another out, making each of the two species more robust together than apart, says McDaniel.
The findings are also interesting from a prevention standpoint, according to McDaniel. “If you were able to vaccinate for H. influenzae, for example, it may remove the signal that allows M. catarrhalis to persist in that environment, and potentially remove two microbes at once,” he says.