A ‘living medicine’ has been created to tackle drug-resistant lung infections.
The breakthrough offers a new strategy to combat the leading cause of mortality in hospitals.
In experiments, it worked on mice infected with pneumonia.
Antibiotic resistant bugs are one of the biggest threats facing mankind, according to the World Health Organisation.
The treatment involves using a modified version of the bacterium Mycoplasma pneumoniae.
It removes its ability to cause disease by repurposing it to attack the infection instead.
The modified bacterium is used in combination with low doses of antibiotics that would otherwise not work on their own.
It doubled survival rate in the lab rodents. A single, high dose showed no signs of toxicity.
Once the therapy had finished its course, the innate immune system cleared the modified bacteria in a period of four days.
Corresponding author Dr Maria Lluch, of the International University of Catalonia, said: “We have developed a battering ram that lays siege to antibiotic-resistant bacteria.
“The treatment punches holes in their cell walls, providing crucial entry points for antibiotics to invade and clear infections at their source.
“We believe this is a promising new strategy to address the leading cause of mortality in hospitals.”
P. aeruginosa infections are difficult to treat because the bacteria lives in communities that form biofilms.
Biofilms can attach themselves to various surfaces in the body, forming impenetrable structures that escape the reach of antibiotics.
They can grow on the surface of endotracheal tubes used by critically-ill patients who require mechanical ventilators to breathe.
This causes ventilator-associated pneumonia - VAP - a condition which affects one in four patients who require intubation.
Incidence exceeds 50 percent for patients intubated because of severe Covid-19.
VAP can extend the duration in intensive care unit for up to 13 days and kills up to one in eight patients.
The Spanish team engineered M. pneumoniae to dissolve biofilms by equipping it with the ability to produce various molecules including pyocins.
They are toxins naturally produced by bacteria to kill or inhibit the growth Pseudomonas bacterial strains.
To test its efficacy, they collected P. aeruginosa biofilms from the endotracheal tubes of patients in intensive care units.
They found the treatment penetrated the barrier and successfully dissolved the biofilms.
The researchers plan further tests before clinical trials.
The treatment is expected to be administered using a nebuliser, a device that turns liquid medicine into a mist which is then inhaled through a mouthpiece or a mask.
It opens the door to creating new strains of the bacteria to tackle other types of respiratory diseases such as lung cancer or asthma.
Co author Professor Luis Serrano said: “The bacterium can be modified with a variety of different payloads – whether these are cytokines, nanobodies or defensins.
“The aim is to diversify the modified bacterium’s arsenal and unlock its full potential in treating a variety of complex diseases.”
The researchers are also using their expertise in synthetic biology to design new proteins that can be delivered by M. pneumoniae.
They are using these proteins to target inflammation caused by P. aeruginosa infections.
Though inflammation is the body’s natural response to an infection, excessive or prolonged inflammation can damage lung tissue.
The inflammatory response is orchestrated by the immune system, which release mediator proteins such as cytokines.
One type of cytokine – IL-10 – has well-known anti-inflammatory properties and is of growing therapeutic interest.
Co corresponding author Dr Ariadna Montero Blay said: “Live biotherapeutics such as M. pneumoniae provide ideal vehicles to help overcome the traditional limitations of cytokines and unlock their huge potential in treating a variety of human diseases.
“Engineering cytokines as therapeutic molecules was critical to tackle inflammation. Other lung diseases such as asthma or pulmonary fibrosis could also stand to benefit from this approach.”
The study was published in the journal Nature Biotechnology.
