Tuberculosis-causing mycobacteria stiffen cell membranes to avoid destruction, but the discovery opens new pathways for treatment.
RT’s Three Key Takeaways:
Membrane-Stiffening Survival Strategy: Tuberculosis-causing bacteria release lipid-filled extracellular vesicles that stiffen immune cell membranes, preventing phagosomes from fusing with lysosomes and allowing the bacteria to survive inside cells.
Lipid-Driven Immune Dysfunction: The study reveals a novel lipid-centric mechanism of immune evasion, showing that bacterial lipids alone can physically alter host cell membranes and weaken immune defenses, even in nearby uninfected cells.
New Therapeutic Targets: By identifying vesicle production and membrane stiffening as key survival tools, the findings suggest new treatment strategies aimed at blocking these processes to help immune cells effectively eliminate infection.
Scientists have uncovered an elegant biophysical trick that tuberculosis-causing bacteria use to survive inside human cells, a discovery that could lead to new strategies for fighting one of the world’s deadliest infectious diseases.
Tuberculosis kills more than a million people each year and remains a major public health crisis, particularly in Asia, Africa and Latin America. The disease is caused by mycobacteria, which have evolved sophisticated ways to hijack human immune cells and avoid being destroyed.
“Tuberculosis is rampant in India,” said Ayush Panda, formerly a graduate student in the laboratory of Mohammed Saleem at the National Institute of Science Education and Research, India. “I grew up in a state where tuberculosis outbreaks are a major problem, and I was always curious about how these diseases spread. That’s what drew me to this research.”
Credit: Image courtesy of Ayush Panda
Mycobacteria have evolved sophisticated ways to hijack human immune cells and avoid being destroyed. Specifically, they stiffen the internal membrane to prevent the digestive enzymes within lysosomes from destroying the bacteria.
The research, which will be presented at the 70th Biophysical Society Annual Meeting in San Francisco from February 21–25, 2026, and was recently posted on bioRxiv, reveals that mycobacteria release tiny packages called extracellular vesicles that fuse with the membranes of immune cells. These vesicles contain specialized lipids—fatty molecules—that make the cell membrane more rigid.
Normally, when our immune cells engulf harmful bacteria, they trap them in a compartment called a phagosome, which then fuses with another compartment called a lysosome. Lysosomes contain digestive enzymes that break down and destroy the bacteria. However, the team discovered that by stiffening the phagosome membrane, mycobacteria prevent this fusion from occurring—essentially building a protective bunker around themselves inside our own cells.
“If the membrane becomes more rigid, it becomes much harder for the phagosome to fuse with the lysosome,” Panda explained. “It’s an elegant biophysical mechanism: the bacteria remodel the membrane architecture to escape the very process that would have killed them.” The researchers also found that these vesicles are not limited to infected cells. They can affect nearby immune cells, weakening them even before they come into contact with the bacteria.
What makes this discovery particularly significant is that it represents an entirely new way of understanding how mycobacteria survive. Previous research focused primarily on proteins that the bacteria disrupt. This study takes a lipid-centric approach, showing that the introduction of bacterial lipids into host cell membranes is sufficient to induce immune dysfunction.
“The most surprising finding was when we introduced mycobacterial lipids into membranes that mimic the host phagosome, we saw remarkable physical changes—the membrane properties were completely altered,” Panda said.
The researchers also observed similar extracellular vesicle-mediated membrane effects in Klebsiella pneumoniae and Staphylococcus aureus, suggesting an evolutionarily conserved strategy among pathogens. The findings open several promising avenues for developing new treatments. Researchers could potentially target the proteins involved in the production of these bacterial vesicles or find ways to counteract the membrane-stiffening effects.
“Now that we understand how the bacteria protect themselves, we can start looking for ways to stop them,” Panda said. “If we can block the bacteria from stiffening those membranes, our immune cells might be able to do their job and stop the infection.”