Scientists thought bacteria were harmless – they were wrong

An international study led by scientists from Singapore is discovering that bacteria previously thought to be harmless can make existing lung diseases worse.

This was discovered by a team of international scientists Neisseria – a genus of bacteria that lives in the human body – is not as harmless as previously thought. In fact, it can cause infections in patients with bronchiectasis, asthma, and chronic obstructive pulmonary disease (COPD).

In a landmark study published September 14, 2022, in cell host & microbe, The team showed conclusive evidence of this Neisseria -types can cause lung disease and are associated with worsening bronchiectasis (a type of lung disease) in patients. The scientists were led by Nanyang Technological University, Singapore (NTU Singapore).

Bronchiectasis is a long-term condition in which the airways of the lungs expand abnormally for unknown reasons in up to 50 percent of Singapore patients. The disease is up to four times more common among Asians compared to their Western counterparts and can occur even after recovery from tuberculosis.^[1] In Singapore, 420 patients with in-hospital bronchiectasis were described in Tan Tock Seng Hospital in 2017.^[2] The incidence rate is 10.6 per 100,000 and increases sharply with age.

Despite its prevalence in the elderly, most cases of bronchiectasis have no apparent cause and the condition occurs spontaneously and without warning.^[3]

The international team – made up of researchers and hospitals in Singapore, Malaysia, China, Australia and the UK – worked together to solve the mystery of why bronchiectasis is significantly more likely to worsen in older Asian patients (see Annex) — led by LKCMedicine Associate Professor Sanjay Chotirmall, Provost’s Chair in Molecular Medicine, compared disease and infection data from 225 patients with bronchiectasis of Asian origin (Singapore and Malaysia) with those of bronchiectasis patients in Europe.

Neisseria: not so harmless after all

While Neisseria Species are known to cause meningitis and gonorrhea, but are not known to infect the lungs. Through detailed identification and careful characterization, the research team found this out Neisseria dominated the microbiome of Asian patients with worsening bronchiectasis.

In particular, bronchiectasis patients with predominant amounts of a subset of Neisseria called Neisseria subflava (N. subflava), experienced more severe illness and repeated infections (exacerbations) compared to patients with bronchiectasis without such high levels. Neisseria.

After further investigations with experimental cell and animal models, the research team confirmed this N. subflava causes cell destruction leading to inflammation and immune dysfunction in patients with bronchiectasis with this bacterium.

Shown is evidence of Neisseria (N. subflava) in the lung tissue of patients with bronchiectasis. The N. subflava detection is shown in red and the cell nuclei of the respiratory tract are shown in blue. Credit: Cell Host & Microbe

Prior to this discovery, Neisseria was not thought to cause lung infection or serious illness in patients with bronchiectasis.

LKCMedicine lead investigator Prof Chotirmall said: “Our results have shown for the first time that worse clinical outcomes such as greater disease severity, poorer lung function and high rates of recurrent infections in patients with bronchiectasis are closely associated with the bacterium Neisseria and Neisseria in that this finding is particularly important for Asian patients.”

“This discovery is significant because it may change the way we treat our bronchiectasis patients with this bacterium. Doctors must now consider Neisseria as a potential “culprit” in patients whose condition worsens despite treatment, and conduct tests to identify those who may be harboring this type of bacteria in their lungs. We hope that early detection will lead to personalized therapy and therefore better disease outcomes for Asian patients with this devastating disease,” said Prof Chotirmall, who is also Associate Dean (Faculty Affairs) at LKCMedicine.

This study reflects NTU’s efforts as part of NTU2025, the university’s five-year strategic plan to address the grand challenges facing humanity such as human health. Conducted by international researchers from different disciplines, the study also highlights NTU’s strength and focus on interdisciplinary research.

Broader relevance of Neisseria

Aside from the link between Neisseria and severe bronchiectasis, the research team led by NTU also discovered the presence of the same bacteria in other more common chronic respiratory conditions such as severe asthma and chronic obstructive pulmonary disease (COPD) – a condition that causes blockage in airflow and breathing – related problems.

Using next-generation sequencing technologies, the team also tried to study where this bacterium might have come from, sampling the homes of patients with bronchiectasis with high levels of Neisseria in her lungs. The researchers found the presence of the bacteria in the home environment, suggesting that indoor living space and possibly the tropical climate could favor the presence of these bacteria in the Asian environment.

What is Neisseria?

That Neisseria Bacterial species have often been identified as the cause of sexually transmitted infections such as gonorrhea, but also meningitis – an inflammation of the fluid and membranes that line the brain and spinal cord. its subspecies N. subflavaHowever, it is known to be present in the oral mucosa, pharynx, and upper respiratory tract of humans with no prior known association with lung infections.

This family of bacteria has always been considered harmless to humans, and infections from them have not been described – until now.

Co-author Professor Wang De Yun, from the Department of Otorhinolaryngology at the Yong Loo Lin School of Medicine, National University of Singapore, said: “It is encouraging to see that in identifying the Neisseria bacterial species as a Cause of worsening bronchiectasis, the unlikely culprit, not initially considered a threat. This is a powerful reminder that we shouldn’t be too complacent when it comes to conducting research and take more proactive steps in exploring various possibilities, as every seemingly innocent element poses a threat to our bodies and our overall health could represent.”

Co-author Andrew Tan, Associate Professor of Metabolic Disorders at LKCMedicine, said: “The reverse translational approach taken in this work was critical to our success. From the “bedside” where we examined real patient experiences, we then worked backwards to uncover the biological process of the bacteria. Thanks to the interdisciplinary nature of the study, the team was able to interact with members from different research disciplines, providing an enjoyable experience while gaining unique insights into the disease.”

The researchers now want to carry out further studies and clinical trials Neisseria Eradication of the microbiome by the newly formed LKCMedicine Center for Microbiome Medicine attempting to assess the benefits of targeting and treatment Neisseria with antibiotics at initial detection in the hope that this will lead to better clinical outcomes for patients with chronic respiratory disease.

Relation: “Neisseria Species as pathobionts in bronchiectasis” by Liang Li, Micheál Mac Aogáin, Tengfei Xu, Tavleen Kaur Jaggi, Louisa LY 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 AB Wark, Brian Oliver, Daniela I Drautz-Moses, Stephan C Schuster, Nguan Soon Tan, Mingliang Fang, James D Chalmers, and Sanjay H Chotirmall, September 14, 2022, Cell Host & Microbe.
DOI: 10.1016/j.chom.2022.08.005

Remarks

1. “Trends in Bronchiectasis Among Medicare Beneficiaries in the United States, 2000 to 2007” by Amy E. Seitz, MPH; Kenneth N. Olivier, MD, MPH; Jennifer Adjemian, PhD; Steven M. Holland, MD and D. Rebecca Prevots, PhD, MPH, August 1, 2012, chest diary.
   DOI: 10.1378/chest.11-2209
2. “Epidemiology and Economic Burden of Bronchiectasis Requiring Hospitalization in Singapore” by Hwee Pin Phua, Wei-Yen Lim, Ganga Ganesan, Joanne Yoong, Kelvin Bryan Tan, John Arputhan Abisheganaden and Albert Yick Hou Lim, August 12, 2021, ERJ Open Research.
   DOI: 10.1183/23120541.00334-2021
3. “Geographical Variation in the Etiology, Epidemiology, and Microbiology of Bronchiectasis” by Ravishankar Chandrasekaran, Micheál Mac Aogáin, James D. Chalmers, Stuart J. Elborn, and Sanjay H. Chotirmall, May 22, 2018, BMC Lung Medicine.
   DOI: 10.1186/s12890-018-0638-0

Annex

List of collaborating institutions

• Department of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen, China
• Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
• Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
• Laboratory of Biochemical Genetics, Department of Biochemistry, St James’s Hospital, Dublin, Ireland
• Department of Clinical Biochemistry, School of Medicine, Trinity College Dublin, Dublin, Ireland
• Faculty of Civil and Environmental Engineering, Nanyang Technological University, Singapore
• College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
• University of Dundee, Ninewells Hospital, Medical School, Dundee, Scotland
• Department of Otorhinolaryngology, Translational Research Program in Infectious Diseases, Yong Loo Lin School of Medicine, National University of Singapore
• Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore
• Respiratory and Critical Care Unit, Tan Tock Seng Hospital, Singapore
• Respiratory and Critical Care Unit, Changi General Hospital, Singapore
• University of Kebangsaan Malaysia, Kuala Lumpur, Malaysia
• Department of Respiratory Medicine and Critical Care, Peking University Shenzhen Hospital, Shenzhen, China
• Priority Research Center for Healthy Lungs, Hunter Medical Research Institute, School of Medicine and Public Health, University of Newcastle, NSW, Australia
• Department of Respiratory and Sleep Medicine, John Hunter Hospital, New Lambton Heights, NSW, Australia
• Woolcock Institute of Medical Research, University of Sydney, Australia
• School of Life Sciences, University of Technology Sydney, Australia
• Singapore Center for Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, Singapore
• School of Biological Sciences, Nanyang Technological University, Singapore
• Department of Environmental Science and Engineering, Fudan University, Shanghai, China