Recurrence of middle ear infection can be prevented by boosting levels of antimicrobial proteins that are already there, as well as eliminating bacteria’s DNA
The finding came from a team in The Research Institute at Nationwide Children’s Hospital who set out to observe how an immune defense protein commonly found in the middle ear communicates with a structure that secures a community of bacteria.
The bacterium is called nontypeable Haemophilus influenza (NTHI) and is responsible for a variety of diseases of both the lower and upper airways, such as middle ear infection.
Similar to other microorganisms, NTHI can create a strong colony of bacteria, known as a biofilm. This permits the bacteria to avoid the person’s immune system, while keeping safe from antibiotics and other treatments that try to destroy them.
Gram-positive and Gram-negative bacteria can be killed by an antimicrobial defense protein, called human beta-defensin-3, that is expressed in the middle ear of humans and other mammals. According to prior studies, the host’s ability to control the bacteria in the upper airway changes if the expression of beta-defensis is disrupted, and the infection gets even worse.
Human beta-defensin-3 might lose its strength to destroy NTHI if it gets stuck within the extracellular DNA that makes up a biofilm’s outer layer, stopping its connection with bacteria within the biofilm, the team hypothesized.
Lauren O. Bakaletz, Ph.D., director of the Center for Microbial Pathogenesis, explained:
“Antimicrobial host defense proteins, like human beta-defensin-3, have been shown to bind to non-host DNA. This interaction has an impact on the defense protein’s ability to function.”
While analyzing the animal model of middle ear infection, Dr. Bakaletz and his colleagues discovered that in the biofilms that were created during infection, the animal’s defense peptides and bacterial DNA were found together. The team also realized that the defense peptide was mainly co-localized with the extracellular DNA of the biofilm.
When a concentration of human-beta defensin-3, which is normally found in a child’s middle ear with an active infection, was released to the bacteria that cause ear infections, the peptide destroyed 100% of the NTHI. However, the destruction ended when extracellular DNA was presented to the response.
“These data support the conclusion that the killing activity of the antimicrobial defense protein was decreased in an NTHI-induced biofilm due to its interaction with eDNA,” said Dr. Bakaletz, leading author and professor of Pediatrics and Otolaryngology at The Ohio State University College of Medicine.
After taking away the extracellular DNA from the biofilm, the team found that it recovered the killing activity of the defense peptide.
“The ability to restore antimicrobial defense protein activity is encouraging, since biofilms are resistant to most treatments, including traditional antibiotics,” Dr. Bakaletz said.
This research should encourage scientists to create a new treatment regimen that can aim for biofilms created by NTHI during middle ear infection.
One strategy may be to disrupt bacertial DNA by administering a therapeutic agent along with human beta-defensin-3 to the middle ear of a child with chronic, recurrent infection. The same pathway could be used that doctors use to target the middle ear during ear tube surgery (a therapy for chronic ear infections).
Dr. Bakaletz concluded:
“This approach would likely bolster the ability of the innate immune system to manage NTHI-induced biofilms, avoiding the need for antibiotics or empowering the use of antibiotics we already have in our arsena. Doing so could help diminish the recurrent nature of middle ear infection.”
Written by Sarah Glynn