Antibiotic-resistant bacteria growing on the surfaces of medical implants have been treated with ‘living medicine,’ according to researchers. The treatment was developed by removing the ability of a common bacteria to cause disease and repurposing it to attack harmful microbes instead. The findings are an important first step toward developing new treatments for these infections, which account for 80% of all infections acquired in hospital settings.
The Centre for Genomic Regulation (CRG) and Pulmobiotics S.L researchers developed the first ‘living medicine’ to treat antibiotic-resistant bacteria that grow on the surfaces of medical implants. The treatment was developed by removing the ability of a common bacteria to cause disease and repurposing it to attack harmful microbes instead.
The experimental treatment was tested on infected catheters in vitro, ex vivo, and in vivo, and it effectively treated infections in all three methods. Injecting the therapy under the skin of mice, according to the authors, treated infections in 82 percent of the treated animals.
The findings are an important first step toward developing new treatments for infections that affect medical implants like catheters, pacemakers, and prosthetic joints. These are antibiotic-resistant and account for 80 percent of all infections acquired in hospital settings.
Bacteria are ideal vehicles for ‘living medicine,’ as they can transport any therapeutic protein to treat the cause of a disease. One of the most significant advantages of the technology is that once at their destination, bacterial vectors provide continuous and localized production of the therapeutic molecule.
Professor Luis Serrano
The findings were published in the journal Molecular Systems Biology today. The “la Caixa” Foundation through the CaixaResearch Health call, the European Research Council (ERC), the MycoSynVac project under the EU’s Horizon 2020 research and innovation programme, the Generalitat de Catalunya, and the Instituto de Salud Carlos III have all contributed to this work.
The new treatment specifically targets biofilms, which are colonies of bacterial cells that adhere to a surface. Biofilms thrive on the surfaces of medical implants, where they form impenetrable structures that prevent antibiotics or the human immune system from destroying the bacteria embedded within. Antibiotic resistance in biofilm-associated bacteria can be a thousand times greater than in free-floating bacteria.
One of the most common species of biofilm-associated bacteria is Staphylococcus aureus. S. aureus infections do not respond to standard antibiotics, necessitating surgical removal of any infected medical implants. Alternative therapies include the use of antibodies or enzymes, but these are broad-spectrum treatments that are extremely toxic to normal tissues and cells, resulting in unintended side effects.
The study’s authors hypothesized that introducing living organisms that directly produce enzymes in the vicinity of biofilms is a safer and less expensive method of treating infections. Bacteria are an ideal vector because their genomes are small and easily modified through simple genetic manipulation.
The researchers chose to engineer Mycoplasma pneumoniae, a common species of bacteria that lacks a cell wall, to make it easier to release therapeutic molecules that fight infection while also helping it avoid detection by the human immune system. Other benefits of using M. pneumoniae as a vector include its low risk of acquiring new abilities and its inability to transfer any of its modified genes to other microbes in the vicinity.
M. pneumoniae was first engineered to be non-pathogenic. Further modifications caused it to produce two distinct enzymes capable of dissolving biofilms and attacking the cell walls of the bacteria embedded within. The bacteria was also modified so that it secretes antimicrobial enzymes more efficiently.
Because M. pneumoniae is naturally adapted to the lung, the researchers hope to use the modified bacteria to treat biofilms that form around breathing tubes first. “Based on synthetic biology and live biotherapeutics, our technology has been designed to meet all safety and efficacy standards for use in the lung, with respiratory diseases being one of the first targets. Our next challenge will be to address large-scale production and manufacturing, and we anticipate beginning clinical trials in 2023 “Mara Lluch, co-corresponding author of the study and Chief Science Officer of Pulmobiotics, explains.
Other diseases may benefit from the modified bacteria in the long run. “Bacteria are ideal vehicles for ‘living medicine,’ as they can transport any therapeutic protein to treat the cause of a disease. One of the most significant advantages of the technology is that once at their destination, bacterial vectors provide continuous and localized production of the therapeutic molecule. Our bacteria, like any other vehicle, can be modified to carry different payloads that target different diseases, with potentially more applications in the future” says ICREA Research Professor Luis Serrano, Director of the CRG and study co-author.
