Tuberculosis Cord-Like Bacterial Aggregates Revealed in Breakthrough Study

October 24, 2023 - In a landmark study recently published in the esteemed journal Cell, researchers have unraveled how Mycobacterium tuberculosis (MTB), the causative agent of tuberculosis, forms cord-like structures crucial for its pathogenicity and antibiotic resistance. This pioneering investigation sheds new light on the biophysical mechanisms behind these bacterial cords and their impact on tuberculosis infections.

For nearly eight decades, the peculiar ability of MTB to create snake-like cord structures has puzzled scientists. The groundbreaking study, authored by a team led by senior author Vivek Thacker, previously at the Global Health Institute at École Polytechnique Fédérale de Lausanne (EPFL) in Switzerland and now based at the Department of Infectious Diseases at Heidelberg University in Germany, provides deep insights into this phenomenon.

"Our work clearly showed that cord formation is important for infection and why this highly ordered architecture might be important for pathogenesis," Vivek Thacker told Science Daily, highlighting the critical significance of the study.

The research employed a multi-faceted approach, including innovative technology like a lung-on-chip model, to observe the initial interaction between MTB and host cells at the lung's air–liquid interface. This novel technique unveiled the prominence of cord formation during early infection. Additionally, the team employed a mouse model that mirrors human tuberculosis pathologies, allowing them to scrutinize tissue using confocal imaging and confirm that cord formation occurs early in infection in vivo.

The findings of this comprehensive study have provided fresh insights into how these bacterial cords interact with and compress the cell nucleus, the ensuing impact on the immune system, and the connections between host cells and epithelial cells. It has also elucidated the consequences of cord formation on the alveoli in the lungs and how these structures enhance resistance to antibiotic therapy.

One of the co-authors, Melanie Hannebelle, who is now at Stanford University, emphasized, "Understanding how forces at the cellular and tissue level or crowding at the molecular level affects cell and tissue function is therefore important to develop a complete picture of how biosystems work."

The study has introduced a paradigm shift in understanding tuberculosis pathogenesis by viewing MTB infection as aggregates rather than single bacteria. Senior author Vivek Thacker commented, "By thinking of MTB in infection as aggregates and not single bacteria, we can imagine new interactions with host proteins for known effectors of MTB pathogenesis and a new paradigm in pathogenesis where forces from bacterial architectures affect host function."

Looking forward, the research community aims to delve deeper into the implications of cord formation, such as its potential impact on known MTB pathogenesis effectors located on the MTB cell wall. Furthermore, researchers plan to investigate how tight-packing within these bacterial clumps may lead to a protective effect against antibiotics, a crucial aspect as antibiotic resistance looms large in treating tuberculosis.

"Antibiotic therapy is the mainstay of treatment for tuberculosis infections, but therapeutic regimens are long and complicated, with an increasing threat of drug resistance," remarked Richa Mishra, one of the first authors of the study and currently at EPFL's Global Health Institute. "There is a recognized need for host-directed therapies or therapies that inhibit specific virulence mechanisms that can shorten and improve antibiotic therapy."

This groundbreaking research enhances our understanding of tuberculosis and provides hope for more effective treatment strategies, potentially reducing the burden of this deadly respiratory infection on a global scale. As future studies unravel the intricacies of cord-like bacterial aggregates, healthcare professionals may soon have a better arsenal in the battle against tuberculosis.