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Tuesday, May 17, 2022

Breakthrough research into killer bacteria set to leave many elders breathing much easier

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Researchers have discovered a way to kill a type of bacteria that causes millions of respiratory infections in children and the elderly, paving the way for more effective treatment.

Through their clinical research, just published in PLOS Pathogens, University of Queensland (UQ) researchers were able to deactivate a protein critical to the survival of Haemophilus Influenzae bacteria, which colonises the respiratory tract from early childhood.

Whilst not initially a problem for most people, this bacteria can contribute to severe respiratory illness and death in vulnerable populations in the event it ‘switches character’.

Associate Professor Ulrike Kappler, a professor in biochemistry and molecular biology at UQ, says this phenomenon is reminiscent of the classic ‘Dr Jekyll and Mr Hyde’ story.

“Most of the time, these bacteria are harmless inhabitants of the respiratory tract, but they have the potential to shift their behaviour and cause diseases such as pneumonia and middle ear infections,” Kappler says.

Associate Professor Ulrike Kappler says that the bacteria Haemophilus Influenzae resembles “Dr Jekyll and Mr Hyde”, laying dormant most of time but dangerous once it “switches character”.

Kappler tells Aged Care News that whilst the underlying causes for this sinister ‘flipping’ effect is somewhat of a mystery, underlying respiratory-system vulnerabilities may be relevant.

“What exactly causes H. influenzae to ‘flip the switch’ is not really known,” she says.

“However, the infections tend to be particularly common in individuals where the function of the lung is impaired in some way.”

Kappler and her team’s research may prove effective in stemming a large number of pneumonia cases and both adults and children alike.

“The bacterium we work with, causes between 25-38 per cent of ‘community acquired ‘pneumonia in adults.

“[That is], pneumonia that people pick up outside of being in a hospital while they are just going about their daily life,” she says.

“Haemophilus influenzae infections tend to be particularly common in older people (>50 years), the elderly, young children, and indigenous populations around the world.”

The infection is a common problem for those with existing respiratory conditions such as asthma, cystic fibrosis, chronic obstructive pulmonary disease (COPD) and, more recently, those recovering from COVID-19.

“Treatment of COPD cost about $937 million in 2018,” Kappler notes.

“With treatment of lower respiratory tract infections,including pneumonia caused healthcare expenditure of $1661 million in the same year.”

Deactivating the bacteria through a discovery of an enzyme necessary for its survival, Kappler says her team now can begin working on targeted therapeutics to be administered to patients upon infection with the noxious, activated form of the bacteria.

“By deactivating the ‘LldD’ protein in Haemophilus to starve the bacteria of key nutrients, the population of damaging bacteria present during infection collapsed, with more than 99.9 per cent eliminated,” Kappler says.

“Together with our collaborators we will be looking for possible inhibitors of the LLdD enzyme that could be administered to inhibit the bacteria during infection.

“We will also further investigate the highly specialised nutritional profile of H. influenzae to identify additional new targets.”

While observing its feeding habits, the researchers also made some surprising discoveries about how the bacteria interacts with the body.

“Our research found that the bacteria do not compete with human cells for the use of glucose to generate energy, and instead use ‘waste products’ such as lactate, which human cells produce in large amounts.

“Surprisingly, Haemophilus also use the human cellular waste products against us by converting them into a form that tricks our immune system to ignore them, meaning our body is unable to keep their numbers in check.”

Jennifer Hosmer, a PhD candidate at UQ, says that the findings were an important first step towards new treatments for people with serious respiratory infections.

“This is really vital information that will inform future research into how to treat and eliminate Haemophilus influenzae and other disease-causing bacteria in the respiratory tract,” Hosmer says.

“It’s a really exciting time, and we feel we’re another step closer to solving the puzzle of how to treat respiratory diseases and infections that afflict millions of people across the globe.”

There are more than 77,500 pneumonia hospitalisations in Australia each year.

The Lung Foundation Australia notes that older Australians are especially vulnerable, with the average hospital stay for those aged over 65 being seven days longer than younger Australians.

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