Revolutionary ‘Living Medicine’ Developed to Combat Drug-Resistant Lung Infections

According to a research report in Science Daily, scientists show how bacteria may be manipulated to function as a “living medicine” in the lungs. Mice with acute lung infections lived twice as long as untreated mice due to the superior treatment they got. There was no evidence of toxicity in the lungs four days after therapy ended, and the immune system had cleared any leftover particles.

The therapy successfully removed biofilms from the endotracheal tubes of patients suffering from ventilator-associated pneumonia, a common cause of death in intensive care units. Consequently, these bacteria might treat various lung disorders such as cancer, asthma, and pulmonary fibrosis.

In the therapy, Mycoplasma pneumoniae, a bacterium, is employed; it has been genetically engineered to remove its destructive properties and instead focus on P. aeruginosa. Weak doses of antibiotics that would typically be worthless are administered with the mutant bacteria.  

The drug was tested on mice and revealed that it significantly decreased lung infections. After receiving the “living medication,” twice as many mice lived as after getting a placebo. There were no pulmonary effects when a single high therapy dosage was provided. The innate immune system efficiently eliminated the changed bacteria when the therapy ended in just four days. P. aeruginosa infections are difficult to treat because this bacterium develops communities in biofilms.

Biofilms are bacteria populations adhering to a body surface and producing a protective barrier that antibiotics cannot penetrate. Pseudomonas aeruginosa biofilms can infect the endotracheal tubes of severely sick patients who require mechanical ventilation. Ventilator-associated pneumonia (VAP) affects 9 to 27% of intubated patients. In the most seriously ill patients, Covid-19 has an intubation rate significantly above 50%. For afflicted patients, VAP is related to a 9-13% death rate and an average 13-day prolongation of stay in the ICU. 

The researchers were able to adapt M. pneumoniae to destroy biofilms by enhancing its capacity to make process toxins often generated by bacteria to kill or inhibit the development of Pseudomonas bacterial strains. P. aeruginosa biofilms were collected from the endotracheal tubes of intensive care unit patients to test the efficacy of the treatment. Despite the barrier, the researchers discovered that the therapy might eradicate biofilms.  

“We’ve built a battering ram against microorganisms resistant to antibiotics. Antibiotics can penetrate and eliminate infections deep within the body more efficiently because of the micro punctures caused by the procedure. This is a potential new method for reducing the major cause of death in inpatient hospitals.” Dr. Maria Lluch of Pulmobiotics describes the findings, who is also the co-corresponding author and principal investigator at the International University of Catalonia.  

More testing of the ‘living medication’ is planned before it enters clinical trials to treat VAP. As a result, the liquid medicine will be vaporized using a nebulizer, making it more straightforward to inhale using a mouthpiece or a mask. Mycoplasma pneumoniae is an exceedingly tiny bacterium.

Dr. Luis Serrano, the CRG’s director, proposed employing microorganisms with specific alterations as a “living pharmaceutical” twenty years ago. Dr. Serrano is a well-known expert in the subject of synthetic biology, which is concerned with the study of designing organisms for specific goals. M. pneumoniae, with just 684 genes and no cell wall, is an excellent candidate for focused biological engineering. M. pneumoniae is beneficial for treating respiratory disorders due to its earlier adaptation to lung tissue.

The modified bacteria move straight to the site of an airway infection after being injected. They set up shop like a temporary factory and manufacture various medicinal substances.  

The discovery that M. pneumoniae can guard against lung infections provides the way for developing novel strains of the bacterium to combat many forms of respiratory illness, including lung cancer and asthma. “Payloads such as cytokines, nanobodies, and defenses may be engineered into bacteria. The goal is to optimize the altered microbe’s therapeutic potential against many critical ailments. “ICREA Research Professor Luis Serrano has something to say about it.  

Dr. Serrano and his colleagues utilize synthetic biology to generate novel proteins that M. pneumoniae can carry in addition to the ‘living medication’ they’ve developed. This group uses proteins to decrease the immune response to P. aeruginosa infections.  

Although inflammation is a natural reaction to illness, it can be dangerous if it persists for an extended period or occurs in excessive lung concentrations. The immune system orchestrates the inflammatory response by releasing cytokines and other mediator proteins. IL-10’s anti-inflammatory characteristics are well documented, leading to increased interest in the cytokine as a therapeutic target.