Breath test for TB using β-lactamase‑activated probe

Pulmonary tuberculosis (PTB) remains a major global public health challenge, and existing diagnostic tools often fall short where they are needed most. Current approaches can have suboptimal sensitivity, long turnaround times, high costs, and they frequently rely on sputum samples that are hard to collect from children and people who cannot produce sputum. These limits make early screening and large-scale testing difficult in resource-limited settings. To address these problems, Han Jin and collaborators took a different route: they focused on a trait common to Mycobacterium tuberculosis, the bacteria that cause TB — the expression of the enzyme β-lactamase. The team screened a library of molecular compounds to find something that would react specifically with that enzyme. They identified cefapirin sodium as a specific molecular probe that, when acted on by β-lactamase, produces a detectable gas. The idea is simple: use a small, inexpensive chemical that the bacteria’s enzyme turns into a gas signature, then detect that gas in breath to indicate infection noninvasively and rapidly.

The researchers used systematic screening of a molecular compound library to find a probe that reacts selectively with β-lactamase produced by Mycobacterium tuberculosis. That screening identified cefapirin sodium as a probe that undergoes selective hydrolysis by β-lactamase and releases hydrogen sulfide (H 2 S) as the product. To sense the released gas, they employed a highly sensitive H 2 S sensing system designed to detect the small amounts expected from this enzymatic reaction in breath. To confirm the chemistry and specificity of the reaction, the team validated the results using Gas chromatography-mass spectrometry (GC-MS) and colorimetric assays, which checked both the identity and the amount of the generated hydrogen sulfide (H 2 S). These experiments together demonstrated the feasibility of detecting a β-lactamase-triggered signal from the probe, supporting the concept of a rapid, noninvasive breath-based test for pulmonary tuberculosis.

If the approach proves reliable beyond the laboratory studies described, it could change how screening is done in places with high TB burden. The method is designed to be noninvasive, to deliver a rapid response, and to be low cost — qualities that make it especially attractive in resource-constrained regions where current sputum-based tests are hard to use at scale. By turning a bacterial enzyme signal into a detectable breath marker, the platform offers a new strategy for early, point-of-care, and large-scale screening of pulmonary tuberculosis. While further development and field testing would be needed, the work led by Han Jin points to a promising way to improve early detection and timely intervention, which are both essential for effective TB control in high-burden settings.