Fighting fire with fire: Using genetically reprogrammed bacteria to treat respiratory infections.

Written by Dr. William Johnston, Postdoctoral researcher, Glasgow Caledonian University and Dr. Mark Thomas Shaw Williams, Lecturer in Cell and Molecular Biology, Glasgow Caledonian University.

Respiratory tract infections are infections of parts of the body involved in breathing, such as the sinuses, throat, airways, or lungs. Some examples are the common cold, tonsillitis, and laryngitis.

Respiratory tract infections are of growing concern due to rising death rates and limited treatment options. This occurs as many bacteria responsible for these infections are resistant to current antibiotics, and a large proportion of cases are caused by biofilms.

Biofilms arise when bacteria clump together in a ‘slime-like’ substance making them difficult to be targeted by antibiotics. This is especially common in patients on ventilation in intensive care units (ICU).

One bacteria like this which makes biofilms is P. aeruginosa, related to pneumonia and severe infections in cystic fibrosis. Previous attempts to treat P. aeruginosa biofilms using antibiotics have been largely unsuccessful, leaving few treatment options available for patients who already have a weakened immune system.

A recent research study carried out by Mazzolini and colleagues focussed on using another bacteria called M. pneumoniae to fight P. aeruginosa biofilms. The researchers selected M. pneumoniae because it is responsive to antibiotics and easy to genetically modify.

What did the research find?

In their research published in Nature Biotechnology, the authors successfully reprogram M. pneumoniae giving it the ability to breakdown and kill P. aeruginosa biofilms without M. pneumoniae causing infection itself. This was completed through two steps;

Step 1: They removed genes in M. pneumoniae capable of causing disease, creating a weakened strain suitable for use.

Step 2: They added new genes to this M. pneumoniae strain making it capable of dissolving P. aeruginosa biofilms and then killing it once the biofilm was broken down.

How was this research covered in the media?

This research was featured in an article from The Guardian titled “GM bacteria could combat antibiotic resistance, study suggests”. The article provides a good summary of the research and is well explained with input from the senior author of the study. However, the article headline is slightly misleading because the reprogrammed M. pneumoniae cannot make bacteria that are resistant to antibiotics responsive to them again. The reprogrammed M. pneumoniae provides an alternative treatment option for P. aeruginosa biofilms, but does not make existing antibiotic resistant bacteria any more responsive to antibiotics.  

What will happen with this research in the future?

Taken together, this research provides firm evidence that using a genetically reprogrammed bacteria to treat P. aeruginosa biofilms may be an effective option for respiratory tract infections. However, it is worth stating that this research was performed largely in mice, and whilst the data seem promising, a major challenge will be the transition into human infections, which can take more than ten years to get from discovery to market.