How do Immune cells impact on antibiotic treatments for TB?

“By understanding more about how current antibiotics are impacted by conditions inside of cells, such as acidity, we hope it could help the search for new drugs or better drug combinations.” Max Gutierrez

A research team at the Francis Crick Institute have shown that an antibiotic used to treat tuberculosis (TB) is affected by pH levels in the environment inside macrophage immune cells that target the disease and also engulf the antibiotic.

In their study(1) the researchers developed a fluorescence-based imaging technique for monitoring, in real-time, the effects of experimentally changed pH levels in infected cells. They found that TB is able to maintain and regulate its own pH independently of the pH of the macrophage, providing a defence against the immune system.

They then tested four front-line TB antibiotic treatments to see if they were affected by different acidity levels and found that one type, pyrazinamide, often used as part of the TB treatment regime, is only effective within an acidic environment. 

Pierre Santucci, co-corresponding author and postdoctoral training fellow in the Host-Pathogen Interactions in Tuberculosis Laboratory at the Crick, said: “Understanding that the effectiveness of antibiotics can be impacted by environmental pH levels is really valuable. It underlines the importance of testing new treatments or treatment combinations in conditions which closely mimic what happens inside cells.”

The researchers also found that pyrazinamide affects the ability of TB to regulate its own acidity levels. The drug is an important part of the TB treatment strategy as it reduces the length of time drugs need to be taken for.  

Need for new treatments crucial

Max Gutierrez, senior author and group leader of the Host-Pathogen Interactions in Tuberculosis Laboratory at the Crick, said: “With rising levels of antibiotic resistance globally, finding new, more effective treatments is crucial. This has been challenging, in part because TB lives inside cells, so any treatment has to be able to enter into the cells and work effectively in this intracellular environment.

“By understanding more about how current antibiotics are impacted by conditions inside of cells, such as acidity, we hope it could help the search for new drugs or better drug combinations.”

The researchers will continue this work studying how the environment within TB and macrophages affects antibiotics. The imaging approach developed to monitor pH levels was also said to have potential for adaptation to study other bacteria and parasites.  

The study was published in mbio, March 2022

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