New studies identify how TB processes destroy the lungs and how to protect them


Mycobacterium tuberculosis , which cause TB. Credit: NIAID “width =” 640 “height =” 530 “/>

Scanning electron micrograph of Mycobacterium tuberculosis bacteria, which cause TB. Credit: NIAID

Two new studies have shed unprecedented light on the processes of tuberculosis disease, identifying key genetic changes that cause lung damage and a pharmacological treatment that can speed recovery.

Tuberculosis (TB) is a this has killed more humans than any other, and until last year was the world’s leading infectious killer. Worldwide, an estimated 10 million people develop the disease each year.

The findings are reported in two papers published in the Journal of Clinical Research.

In the first study, a team at the University of Southampton used a new 3D culture system they have developed to observe the changes that occur in TB-infected cells. Unlike the standard 2D laboratory culture system, where the cells are placed on a flat plastic plate, the 3D system uses an engineering technique to suspend them in drops, such as the frog frog. The team found that TB-infected cells in droplets responded very closely to the lung cells of patients with the disease.

This observation has widespread implications for subsequent studies on infectious diseases, including COVID-19.

A second team from the University of Southampton carried out complex sequencing techniques in cells to identify the events through which tuberculosis causes excessive inflammation and damage to the tuberculosis. .

Human genome sequencing methods generate information about tens of thousands of changes in the genes in each sample, making it difficult to figure out which changes are important and which are fortuitous. Southampton’s systems immunology group combined different mathematical approaches, such as clustering algorithms, to reduce it to seven genes that appear to underlie the pulmonary destruction that occurs in TB.

Dr Michaela Reichmann of the University of Southampton, who conducted the study, said: “The integration of modern sequencing techniques with clinical samples allows for an unprecedented view of the mechanisms of the disease, while our system of 3D cell culture allows us to replicate conditions in patients and identify new treatment approaches. “

In the second study, a clinical trial led by Dr. Catherine Ong of the National University of Singapore studied the use of a common antibiotic, doxycycline, to reverse these changes. Phase 2 in 30 patients showed that doxycycline, in combination with TB , reduces the size of the lung cavities and accelerates the markers of lung recovery towards health. These bioinformatics analyzes were performed by the Systems Immunology Group in Southampton.

Treatment was found to be safe, with side effects similar to those experienced by patients on placebo tablets. The study demonstrates the promise of offering a new standard of care that can prevent long-term complications.

Dr. Ong said that “patients with pulmonary TB tend to suffer lung damage after TB, which is associated with mortality and a lower quality of life. Doxycycline is a cheap and widely available antibiotic that can decrease lung damage and potentially improve the quality of life for these patients. “

The team is now looking for funding for a fully fed large-scale Phase 3 trial to verify these findings.

The international team also aims to translate these new ideas into approaches that can shorten treatment from the current six-month minimum and improve the treatment of drug-resistant diseases, which is gradually increasing.

The clinical trial was based on a collaborative network involving the National University of Singapore, the University of Southampton and St George’s London, while the study of basic sciences also involved the African Institute for Health Research. , Durban and Yale and Columbia universities in the United States.

An readily available antibiotic could help curb lung damage from tuberculosis

More information:
Michaela T. Reichmann et al, Integrated transcriptomic analysis of human tuberculosis granulomas and a biomimetic model identifies therapeutic targets, Journal of Clinical Research (2021). DOI: 10.1172 / JCI148136

Citation: New studies identify how tuberculosis processes destroy the lungs and how to protect them (2021, June 15) retrieved June 15, 2021 at html

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