Scientists thought bacteria were harmless – they were wrong

Scientists have discovered that a type of bacteria is not as harmful as previously thought. It can actually cause infections in patients with bronchiectasis, asthma and chronic obstructive pulmonary disease (COPD).

An international study led by Singapore scientists has found that bacteria previously thought to be harmless can exacerbate existing lung diseases.

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

In a historical study, published on September 14, 2022, in host cell and microbe, The team has shown compelling evidence of this Neisseria The species can cause lung disease and is associated with exacerbation of bronchiectasis (a type of lung disease) in patients. The scientists were led by Nanyang Technological University of Singapore (NTU Singapore).

Bronchiectasis is a long-term condition in which the air passages of the lungs become abnormally enlarged for unknown reasons in up to 50 percent of Singapore patients. The disease is four times more common in Asians than its Western counterparts and can also occur after recovery from tuberculosis.[1] In Singapore, research at Tan Tock Seng Hospital described 420 bronchiectasis patients in the hospital in 2017.[2] The incidence is 10.6 per 100,000 and increases strongly with age.

Despite its prevalence among the elderly, there is no clear cause in most cases of bronchiectasis and the condition tends to appear spontaneously and without warning.[3]

To unravel the mystery of why bronchiectasis worsens at a much greater rate among older Asian patients, the international team – which includes researchers and hospitals in Singapore, Malaysia, China, Australia and the UK – has… (We see Attached) Led by LKCMedicine Associate Professor Sanjay Chutermal, University Chair in Molecular Medicine, disease and infection data from 225 patients with bronchiectasis of Asian origin (Singapore and Malaysia) matched to bronchiectasis patients in Europe.

Neisseria: Not harmful after all

While Neisseria The species is known to cause meningitis and gonorrhea, and is not known to infect the lungs. Through detailed identification and careful characterization, the research team found that Neisseria The microbiome of Asian patients with exacerbations of bronchiectasis was controlled.

Specifically, patients with bronchiectasis predominate in amounts from a subgroup of Neisseria Call Neisseria subflava (N. subflava), suffer from more severe disease and frequent infection (exacerbations) when compared to patients with bronchiectasis without such high amounts of Neisseria.

After further investigations using experimental cell and animal models, the research team confirmed that N. subflava It causes cell disruption, leading to inflammation and immune dysfunction in bronchiectasis patients with these bacteria.

Neisseria in lung tissue

In the photo Neisseria (N. subflava) is detected in lung tissue of bronchiectasis patients. Shown in red is the spotting of N. subflava and shown in blue are airway cell nuclei. Credit: Host Cell and Microbe

Prior to this discovery, Neisseria was not considered to be a cause of lung infection or severe disease in bronchiectasis patients.

Lead researcher Professor Chottermal from LKCMedicine said, “Our findings demonstrate, for the first time, that poorer clinical outcomes such as disease severity, poor lung function, and higher recurrent infection rates among patients with bronchiectasis are closely related to Neisseria neisseria and. This finding Especially important for Asian patients.”

“This discovery is important because it could change the way we treat bronchiectasis patients with this bacteria. Doctors will now need to consider Neisseria as a possible ‘culprit’ in patients who get worse despite treatment, and run tests to identify those who may harbor this type of infection. “We hope that early identification of personalized treatment and, in turn, better satisfactory outcomes for Asian patients with this devastating disease,” said Professor Chuttermal, who is also Assistant Dean (Faculty Affairs) at LKCMedicine.

This study reflects NTU’s efforts under NTU2025, the university’s five-year strategic plan that addresses humanity’s major challenges such as human health. The study was conducted by international researchers from various disciplines, and also highlights the strength of the NTU and its focus on interdisciplinary research.

Wider significance of Neisseria

Aside from linking Neisseria and acute bronchiectasis, the NTU-led research team also discovered the same bacteria in other, more common chronic respiratory conditions such as severe asthma and chronic obstructive pulmonary disease (COPD) — a condition that causes airflow and breathing obstruction. Related problems.

Using next-generation sequencing techniques, the team also sought to verify the source of this bacteria and to take samples from the homes of bronchiectasis patients who had large amounts of Neisseria in their lungs. The researchers found the presence of bacteria in the home environment, suggesting that an indoor living space and possibly a tropical climate might favor the presence of these bacteria in the Asian environment.

What is Neisseria?

The Neisseria Bacteria species have commonly been identified as the cause of sexually transmitted diseases such as gonorrhea but also serious meningitis – an infection of the fluid and membranes surrounding the brain and spinal cord. Its subtypes N. subflavaHowever, it is known to be present in the oral mucosa, throat, and upper airway of humans previously without any known connection to lung infections.

This family of bacteria has long been thought to be harmless to humans, and the infection that causes it has not been described – until now.

Co-author, Professor Wang De Yun from the Department of Otolaryngology at Yong Lo Lin School of Medicine, National University of Singapore, said, “It is encouraging to see that we have made progress in identifying Neisseria species as the cause of exacerbations of bronchiectasis, a potential culprit that was not considered Originally a threat. This comes as a powerful reminder that we shouldn’t get too complacent when it comes to doing research and be more proactive in exploring different possibilities, where every seemingly innocent ingredient can be a threat to our bodies and our health in general.”

Co-author Andrew Tan, Associate Professor of Metabolic Disorders from LKCMedicine, said, “The reverse translation approach adopted in this work has been critical to our success. Starting at the ‘bedside’ where we studied real-world patient experiences, then working backwards to reveal the biological process of the bacteria. Thanks to nature’s multiple Specializations to study, the team was able to interact with members of different research disciplines, providing an enjoyable experience while gaining unique insights into the disease.”

The researchers are now looking forward to further studies and clinical trials of Neisseria Eradication of the microbiome by the newly launched LKCM Center for Microbiome Medicine, which seeks to assess the benefits of targeting and treatment Neisseria Using antibiotics at the first discovery, in the hope that it will lead to better clinical outcomes for patients with chronic respiratory diseases.

Reference: “Neisseria Species as pathogens in bronchiectasis” by Liang Li, Michael McAugin, Tengvi Shu, Tavlin Kaur Jaji, Louisa Lee Chan, Jing Kuo, Lan Wei, Shumin Liao, Hong Sheng Cheng, Holly R. Kerr, Alison J. Decker, Kai Sen Tan, Wang De-yun, Mariko Siwe Koh, Thon Haw Aung, Albert Yek Ho Lim, John A. Abishgandin, Tic Bon Lu, Teddy Maharani Hassan, Xiang Long, Peter AP Wark, Brian Oliver, Daniela I. Drewitz Moses, Stefan Schuster , Nguan Son Tan, Mingliang Fang, James D. Chalmers, and Sanjay H. Chutermal, September 14, 2022, Available here. host cell and microbe.
DOI: 10.1016 / j.chom.2022.08.005

Notes

  1. “Trends in bronchiectasis among Medicare recipients in the United States, 2000 to 2007” by Amy E. Seitz, MPH; Kenneth N. Oliver, MD, MPH; Jennifer Adjmian, Ph.D.; Stephen M Holland, MD and Dr. Rebecca Prevots, Ph.D., Master of Public Health, Aug 1, 2012 Available here. chest magazine.
    DOI: 10.1378 / chest.11-2209
  2. “Epidemiology and the Economic Burden of Hospitalized Bronchiectasis in Singapore” by Hwee Pin Phua, Wei-Yen Lim, Ganga Ganesan, Joanne Yoong, Kelvin Bryan Tan, John Arputhan Abisheganaden, Albert Yick Hou Lim, August 12, 2021, Open search ERJ.
    DOI: 10.1183/23120541.00334-2021
  3. “Geographical Variation in the Aetiology, Epidemiology, and Microbiology of Bronchiectasis” by Ravishankar Chandrasekaran, Michel McAugin and James D. BMC Pulmonary Medicine.
    DOI: 10.1186 / s12890-018-0638-0

Attached

List of cooperating institutions

  • Department of Pharmacy, College of Medicine, Southern University of Science and Technology, Shenzhen, China
  • Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
  • Lee Kong Qian College of Medicine, Nanyang Technological University, Singapore
  • Biochemical Genetics Laboratory, Department of Biochemistry, St James’s Hospital, Dublin, Ireland
  • Clinical Biochemistry Unit, Medical School, Trinity College Dublin, Dublin, Ireland
  • School 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 Otolaryngology, Infectious Diseases Translational Research Program, Young Loo Lin School of Medicine, National University of Singapore
  • Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore
  • Department of Respiratory and Critical Care Medicine, Tan Tock Seng Hospital, Singapore
  • Department of Respiratory and Critical Care Medicine, Changi General Hospital, Singapore
  • National University of Malaysia, Kuala Lumpur, Malaysia
  • Department of Respiratory and Critical Care Medicine, Peking University Hospital, Shenzhen, China
  • Healthy Lung Priority Research Center, Hunter Institute for Medical Research, School of Medicine and Public Health, University of Newcastle, New South Wales, Australia
  • Department of Respiratory and Sleep Medicine, John Hunter Hospital, New Lambton Heights, NSW, Australia
  • Woolcock Institute of Medical Research, University of Sydney, Australia
  • College of Life Sciences, University of Technology Sydney, Australia
  • Singapore Center for Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, Singapore
  • College of Biological Sciences, Nanyang Technological University, Singapore
  • Department of Environmental Science and Engineering, Fudan University, Shanghai, China