Key UB Study Explores How H. influenzae Thrives in COPD

Principal investigator Timothy F. Murphy, MD, has been collaborating with Sanjay Sethi, MD, and Michael Buck, PhD, to study and detail the mechanisms that allow non-typeable Haemophilus influenzae (NTHi) to infect and survive in the airways of adults with COPD.

This understanding may lead to the first new drugs in 50 years to reduce infections and save lives.

A new $2.3 million, five-year grant from the National Institute of Allergy and Infectious Diseases funds the latest project, “Persistent H. influenzae in COPD - Virulence, Vaccines and Antibiotic Resistance.”

COPD afflicts nearly 24 million Americans and is the third most common cause of death.

Researchers say NTHi could be an important factor in airway inflammation and impaired pulmonary function — both indicators of the disease.

“H. influenzae is the most important bacterial cause of exacerbations or the worsening of COPD symptoms, and can lead to serious complications,” says Murphy, SUNY Distinguished Professor of medicine and UB senior associate dean for clinical and translational research.

In healthy people, H. influenzae is frequently present in the throat, but does not cause problems, Murphy says.

However, the bacterium “seems to proliferate and flourish in the diseased, lower respiratory airways of patients with COPD,” whose normal protective responses are impaired, he explains.

The investigators aim to learn how NTHi is able to persist from months to years in airways and survive repeated courses of antibiotic therapy. They also will evaluate potential vaccine antigens now under development.

“This is an excellent example of translational research,” notes Murphy.

He and Sethi, professor of medicine and chief of pulmonary, critical care and sleep medicine, say little progress has been made in developing new treatments and preventing infections in COPD, other than antibiotics. Sethi also is a staff physician with the VA Western New York Healthcare System.

The researchers will assess how NTHi survives an onslaught of antibiotics by using an innovative Hollow Fiber Infection Model developed by co-investigator Brian Tsuji, PharmD, associate professor of pharmacy practice in the School of Pharmacy and Pharmaceutical Sciences. 

Tsuji’s model will expose NTHi to levels of antibiotics at the exact levels that occur in COPD patients. 

The researchers will integrate these results with the results of genome analysis to better understand antibiotic resistance and tolerance.

Buck, assistant professor of biochemistry — who oversees the UB Next-Generation Sequencing and Expression Analysis Core Facility — will conduct genome sequencing.

Lab technicians Charmaine Kirkham, Aimee Brauer and Antoinette Johnson also are involved in the study.

The project’s National Institutes of Health grant application scored a perfect 10 — a rare accomplishment that Murphy attributes to several factors:

• the 18-year prospective study is expected to advance the field significantly
• the study, with its level of rigorously characterized bacterial strains, is unique; no other set of strains collected longitudinally — with this level of detailed clinical data tied to each strain — exists
  
• applying such a large amount of state-of-the-art, next-generation sequencing to this unique set of strains has not been feasible until recently
• determining genome sequences on this large set of well-characterized strains will likely yield new, unexpected results

The current study represents the 28th year of the grant, which has been renewed every three to five years through a competitive process.