IN BRIEF

Using Genomics to Unlock Secrets of Recurrent Ear Infections

April 28, 2020
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Nontypeable Haemophilus influenzae (NTHI) is responsible for many acute and recurrent infections in children, such as otitis media.

Otitis media – middle ear infection – is a common type of recurrent infection in children, with as many as 700 million acute cases and 300 million recurrent cases each year. One type of bacteria responsible for many of these infections is nontypeable Haemophilus influenzae (NTHI). Infections from NTHI are not limited to otitis media; these bacteria can also be problematic for people with cystic fibrosis and other chronic conditions affecting the respiratory tract.

During a chronic or recurrent infection, bacteria must adapt to the ever-changing environment in the host. Bacterial microevolution is one type of adaptation that helps bacteria survive within the host.

A recent study, published in Cell Reports, by researchers from the Abigail Wexner Research Institute (AWRI) at Nationwide Children’s Hospital, used a preclinical model of otitis media to determine the potential role for microevolution of NTHI during sequential episodes of the disease.

The work is part of a collaborative effort between Kevin Mason, PhD, and Sheryl Justice, PhD, both principal investigators in the Center for Microbial Pathogenesis in AWRI. The team previously showed that NTHI form intracellular bacterial communities (IBCs) during infections – effectively hiding out in the epithelial cells of the host.

In the current study, they focused on using whole genome sequencing to look for evidence of microevolution.

“Using our model, we were able to sample the bacteria responsible for recurrent infections in individual ears,” says Dr. Mason, who is also an associate professor of Pediatrics at The Ohio State University. “The technique allowed us to show changes in the genomic make up as the environment and disease-state changed.”

The genomic sequencing showed evidence of microevolution of hemoglobin binding and lipooligosaccharide biosynthesis genes. This suggests the adaptation of these systems is critical for infection.

“NTHI can be infectious or commensal,” says Dr. Mason. “These results help us zero in on genes and processes that could be critical in the formation of infections. Ultimately, those processes might be targets for therapies to treat or prevent infections.”

The otitis media-adapted strains promoted increased biofilm formation, inflammation, stromal fibrosis and propensity to form IBCs.

“Remarkably, the IBCs remained even after the infection was clinically resolved,” says Dr. Justice, who is also an associate professor of Pediatrics and Urology at OSU. “This suggests that the intracellular reservoir is a source for recurrent infections.”

Dr. Justice was part of the team who showed the role of bladder cell IBCs in recurrent urinary tract infections.

“We’ve been able to document this phenomenon in different body systems, and different pathogens [E. coli and NTHI],” she says. “Moving forward, we will hopefully be able to find a way to target the IBCs as a means to reduce chronic infections.”

 

Reference:

Harrison A, Hardison RL, Fullen AR, Wallace RM, Gordon DM, White P, Jennings RN, Justice SS, Mason KM. Continuous microevolution accelerates disease progression during sequential episodes of infectionCell Reports. 2020;30(9):2978–2988.e3.

 

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