Engineered Bacteria Tackle Pathogenic Biofilms of another bacteria in Mice to effectively treat lung infections

Amazing stuff! Good news! Ventilator associated pneumonia is particularly nasty: "The mortality in ventilator-associated pneumonia is high despite the availability of effective antibiotics." (Source)

"Mycoplasma pneumoniae are tiny bacteria typically known to cause lung infections. ... Genetically engineered Mycoplasma helped break down biofilms of another pathogenic microbe, Pseudomonas aeruginosa, in a mouse model of ventilator-associated pneumonia and on tube samples taken from human patients ... It is one of the first times that scientists have used live bacteria to treat a lung disease, and is the first therapeutic use of Mycoplasma. ...
Because of their complicated structure, biofilms are often resistant to antimicrobial treatments even when the individual bacteria in the film are not ...

chose Mycoplasma pneumoniae, a bacteria known for infecting the human respiratory system, for their experiments. Unlike many bacteria, M. pneumoniae cannot recombine, making it a safe candidate for bioengineering that won’t spread its modified genome to other bacteria. It also has a relatively small genome and lacks a cell wall, making it less likely to generate an immune reaction.

The researchers removed the pathogenic genes from M. pneumoniae to ensure the bacteria were safe to use. They then assembled sets of engineered genomes in E. coli, which scientists ... use to engineer bacterial treatments for the gut. These genomes contained a one-two punch to tackle the biofilm: a genetic cassette that codes for the production of biofilm-breaking enzymes and the gene for a toxin that can kill P. aeruginosa. They then transferred the genes in the form of isolated DNA to M. pneumoniae. ..."

From the abstract:

"Engineered live bacteria could provide a new modality for treating lung infections, a major cause of mortality worldwide. In the present study, we engineered a genome-reduced human lung bacterium, Mycoplasma pneumoniae, to treat ventilator-associated pneumonia, a disease with high hospital mortality when associated with Pseudomonas aeruginosa biofilms. After validating the biosafety of an attenuated M. pneumoniae chassis in mice, we introduced four transgenes into the chromosome by transposition to implement bactericidal and biofilm degradation activities. We show that this engineered strain has high efficacy against an acute P. aeruginosa lung infection in a mouse model. In addition, we demonstrated that the engineered strain could dissolve biofilms formed in endotracheal tubes of patients with ventilator-associated pneumonia and be combined with antibiotics targeting the peptidoglycan layer to increase efficacy against Gram-positive and Gram-negative bacteria. We expect our M. pneumoniae-engineered strain to be able to treat biofilm-associated infections in the respiratory tract."

Double Agents: Engineered Bacteria Tackle Pathogenic Biofilms in Mice | The Scientist Magazine® Mycoplasma pneumoniae with pathogenic genes replaced by biofilm-degrading ones enhance survival in a mouse model of ventilator-associated pneumonia.

Engineered live bacteria suppress Pseudomonas aeruginosa infection in mouse lung and dissolve endotracheal-tube biofilms

Fig. 5: In vivo treatment of mice with acute respiratory PAO1 infection.