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How Tuberculosis Bacteria Use a Unique Strategy to Survive Immunity

December 1, 2025 by Logan Hamilton Leave a Comment

A Man in Black Suit Jacket Wearing Eyeglasses
Image courtesy of Towfiqu barbhuiya.

Tuberculosis bacteria are like pests that burrow underground and vanish. When pesticides hit, they harden into shells and hide in the soil. They look dead, but later, they erupt and devour everything. A quiet field becomes a feeding ground all over again.

New research published in npj Vaccines shows TB uses similar tricks. The bacteria “play dead” to survive attacks from the immune system. After vaccination, TB changes its behavior to escape destruction. It becomes quiet, stops growing, and hides from immune cells.

Later, the bacteria can wake up and spread inside the host. This reactivation can cause lung disease and infect other people. The tactic helps TB remain the world’s deadliest infectious disease. Each year, TB kills around 1.25 million people worldwide.

How Does TB Escape Immune System Attacks?

To find out how TB survives vaccines, scientists used a method called TnSeq. TnSeq inserts random mutations across the TB genome. Researchers then grow the bacteria in controlled lab conditions. Genetic sequencing shows which mutations were lost during growth.

Lost mutations reveal genes TB needs to survive and grow. Researchers infected mice with a low dose of TB bacteria. Both infected and control mice were exposed to the full library. After two and four weeks, tissues were collected for analysis.

The team then repeated the process in BCG-vaccinated mice. They compared vaccinated and unvaccinated mice side-by-side. This revealed which TB genes mattered most under vaccine pressure.

At two weeks, 41 genes showed reduced mutant survival in vaccinated mice. These genes had various functions but no clear single pathway. Many responded to immune stress from T cells and macrophages.

At four weeks, 36 different genes became more essential for TB. Some were linked to dormancy, stress response, and bacterial persistence. This suggests TB slows growth to survive immune attack longer. Dormancy may help TB escape immunity and remain hidden in the body.

Limitations and Future Research Opportunities

This study focused only on live vaccines against tuberculosis. It did not include newer types like mRNA or viral vector vaccines. Other vaccine routes, like intravenous or mucosal, were also not tested. Future studies should explore these methods alongside TnSeq.

Testing more vaccine types could show new immune system responses. These results could reveal how TB reacts to different immunizations. This would give a broader view of TB survival under immune pressure.

Another limitation is the use of high-dose IV infection in mice. Lower doses that mimic real infections can’t support large mutant libraries. Still, past studies show TnSeq results match aerosol infections well.

TnSeq also can’t directly measure the immune system’s activity. Blood tests, antibody levels, and cytokines may reveal fuller patterns. This could link immune responses to TB gene survival requirements.

Other tools may help clarify how TB avoids immune destruction. Knockout mice or antibody-blocked mice could reveal specific mechanisms. Targeted gene deletions or tagged TB strains could offer clearer insight.

Despite its limits, this study shows the power of TnSeq. It maps how TB survives immune attacks after vaccination. This strategy can help find weak points in the bacteria. Wider use may guide better vaccines against this global threat.

Conclusion

This study reveals how tuberculosis bacteria survive vaccine-induced immune responses. By entering dormancy and shifting gene use, TB evades immune defenses. Understanding these tactics may lead to better vaccines and long-term control.

Have an upcoming trip? Passport Health offers a wide variety of options to help keep you safe from disease, including vaccines. Call or book online to schedule your appointment today.

Logan Hamilton is a health and wellness freelance writer for hire. He’s passionate about crafting crystal-clear, captivating, and credible content that elevates brands and establishes trust. When not writing, Logan can be found hiking, sticking his nose in bizarre books, or playing drums in a local rock band. Find him at loganjameshamilton.com.

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