Genome of Dangerous Pathogen Deciphered in 15-year Study of COPD Patients

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by Diogo Pinto |

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NTHi pathogen in COPD

A 15-year study demonstrated how nontypeable Haemophilus influenzae (NTHi), one of the most important pathogens in chronic obstructive pulmonary disease (COPD), adapts and survives in patients’ airways over time.

The research findings were reported in the journal Proceedings of the National Academy of Sciences, in a study titled “Haemophilus influenzae genome evolution during persistence in the human airways in chronic obstructive pulmonary disease.”

NTHi is a bacterial pathogen that can colonize and infect people by adapting to the environment in human airways. It can persist in COPD patients’ airways for long periods, causing inflammation, impaired lung function, and tissue damage.

COPD is characterized by acute exacerbations, of which about half are thought to be caused by bacteria. NTHi is the most common bacterial cause of COPD exacerbations, and is directly linked to patients’ clinical outcomes.

In this 15-year study conducted by researchers at the University at Buffalo (UB) in collaboration with the Veterans Affairs Western New York Healthcare System, samples from 192 COPD patients were collected, giving researching 269 strains of NTHi to sequence and analyze.

The study’s goal was to provide insights into how NTHi lives and adapts to its host in real time over months or even years.

“Studies of this pathogen up until now have been looking at strains grown in labs or stored in freezers,” Timothy Murphy, MD, State University of New York (SUNY) distinguished professor and senior associate dean for translational research in the Jacobs School of Medicine and Biomedical Sciences at UB, said in a press release.

“The power of our study is that we have 269 strains of the pathogen and we can see what it looked like when the patient first acquired the strain and how it changed its genes to survive in the unique environment of the human airways,” Murphy said. “The genomes are like a looking glass, revealing the pathogen’s secrets to us by showing us how it changed its genes through the years.”

The team believes that such genetic changes may help determine the pathogen’s vulnerabilities and subsequently help set better strategies to eradicate it.

Researchers found that NTHi is like a switch that turns genes on and off, constantly changing which genes are activated based on the environment in the airways.

For example, since the lower airways are nutritionally deprived, NTHi will activate processes to try to scavenge nutrients like iron that it needs in order to survive, Murphy said.

“Now that we’re beginning to understand how the bacterium is able to survive, we can use these molecules that come from the genes we found as drug targets to eradicate the bacterium from the airways,” he said.

“By helping us understand how this pathogen survives in a hostile environment in human airways, this research is helping us develop ways to eradicate the pathogen to improve the lives and health of people with COPD,” he added.