Cell: Bacteria previously considered harmless are now found to exacerbate existing lung disease

An international team of scientists led by NTU Singapore found that Neisseria — a bacterium that lives in humans — is not as harmless as previously thought, and can cause infections

In a landmark study published today in the journal Cell Host & Microbe, the team presented conclusive evidence that Neisseria can cause lung disease and is associated

Bronchiectasis is a long-term condition in which the airway in the lungs is abnormally enlarged

Although bronchiectasis is prevalent in the elderly, no apparent cause is found in most cases, and the condition tends to be spontaneous without warning

To solve the mystery of why the rate of exacerbations of bronchiectasis is significantly higher in older patients in Asia, an international team led by LKCMedicine Associate Professor Sanjay Chotirmall – researchers and hospitals spanning Singapore, Malaysia, China, Australia and the UK (see annex) – compared the disease and infection data of 225 patients with bronchiectasis from Asia (Singapore and Malaysia) with data from patients with bronchiectasis from Europe

Neisseria : Not so harmless after all

Although it is known that Neisseria causes meningitis and gonorrhea, it is not known that they can infect the

Specifically, patients with bronchiectasis who contain large amounts of N.

Through further experimental cell and animal model studies, the team confirmed that Bacillus flavus can cause cell destruction in bronchiectasis patients, leading to inflammation and immune dysfunction

Prior to this discovery, Neisseria was not considered a cause

Lead researcher Professor Chotirmall, from LKCMedicine, said: "Our findings confirm for the first time that poorer clinical outcomes in patients with bronchiectasis, such as more severe disease, poor lung function and higher rates of recurrent infections, are strongly associated with Neisseria and this finding is particularly important

"This finding is significant because it could change the way we treat patients with bronchiectasis with this bacterium

The study reflects NTU's efforts under NTU2025, the university's five-year strategic plan to address major human challenges, such as human health

Wider relevance of Netheria

In addition to linking Neisseria to severe bronchiectasis, the research team led by the National University found the same bacteria in other, more common chronic respiratory diseases, such as severe asthma and chronic obstructive pulmonary disease (COPD), a disease

Using next-generation sequencing technology, the team also tried to investigate where the bacterium might have come from and sampled

What is meningitis?

Neisseria is often thought of as the cause of sexually transmitted infections such as gonorrhea, but is also thought of as meningitis – an inflammation

This family of bacteria has long been considered harmless to humans, and until now, no one has described the infections

Study co-author Wang De Yun, Professor of Otorhinolaryngology, at the Yong Loo Lin School of Medicine at the National University of Singapore, said: "It is encouraging that we have made progress in identifying Neisseria as the cause of worsening bronchiectasis, an unlikely culprit that was not initially considered a threat

Andrew Tan, associate professor of metabolic disorders at LKCMedicine and co-author, said: "The reverse translation method used in this work was critical
to our success.
Start by studying the real clinical practice? Life is the patient's experience, and then we go backwards to discover the biological processes
of bacteria.
Due to the interdisciplinary nature of the research, the team was able to interact with members from different research disciplines, providing an enjoyable experience while gaining unique insights into
the disease.
”

This group of scientists is now conducting further research and clinical trials on eradicating Neisseria from the microbiome through the newly established LKCMedicine Microbiome Medical Center, which is seeking to evaluate the benefits of targeting Neisseria at the time of the first discovery and using antibiotic treatment, in the hope that this will lead to better clinical outcomes
for patients with chronic respiratory diseases.

Liang Li, Micheá l Mac Aogá in, Tengfei Xu, Tavleen Kaur Jaggi, Louisa L.
Y.
Chan, Jing Qu, Lan Wei, Shumin Liao, Hong Sheng Cheng, Holly R.
Keir, Alison J.
Dicker, Kai Sen Tan, Wang De Yun, Mariko Siyue Koh, Thun How Ong, Albert Yick Hou Lim, John A.
Abisheganaden, Teck Boon Low, Tidi Maharani Hassan, Xiang Long, Peter A.
B.
Wark, Brian Oliver, Daniela I.
Drautz-Moses, Stephan C.
Schuster, Nguan Soon Tan, Mingliang Fang, James D.
Chalmers, Sanjay H.
Chotirmall.
Neisseria species as pathobionts in bronchiectasis.
Cell Host & Microbe, 2022; 30 (9): 1311