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A new type of 'living medication' has been developed to treat infection that are resistant to antibiotics.

The first 'living drug' to treat antibiotic-resistant bacteria developing on the surfaces of medical implants has been developed by researchers at the Centre for Genomic Regulation (CRG) and Pulmobiotics S.L. The remedy was developed by removing the ability of a common bacteria to cause sickness and repurposing it to combat harmful germs instead.

Infected catheters were examined in vitro, ex vivo, and in vivo, with the experimental treatment successfully treating infections in all three modalities. Injecting the medication under the skin of mice cured infections in 82 percent of the animals, according to the authors.

The findings are a critical first step in developing novel treatments for infections that harm medical devices like catheters, pacemakers, and prosthetic joints. These infections are antibiotic-resistant and account for 80% of all infections acquired in hospitals.

The findings were published in the journal Molecular Systems Biology today. 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 research.

Biofilms, or colonies of bacteria that adhere together on a surface, are the goal of the new treatment. Biofilms thrive on the surfaces of medical implants, forming impenetrable coatings that prevent antibiotics or the human immune system from killing the microorganisms contained within. Antibiotic resistance in biofilm-associated bacteria can be 1,000 times higher than in free-floating bacteria.

One of the most prevalent biofilm-associated microorganisms is Staphylococcus aureus. Because S. aureus infections do not respond to traditional antibiotics, patients must have any contaminated medical implants surgically removed. Antibodies and enzymes are examples of alternative therapeutics, but these are broad-spectrum remedies that are very toxic to normal tissues and cells, resulting in unwanted side effects.

The study's authors hypothesized that introducing living organisms that produce enzymes directly in the region of biofilms would be a safer and less expensive way to treat illnesses. Bacteria are an ideal vector because their genomes are tiny and easily manipulated through genetic manipulation.

The researchers chose to alter Mycoplasma pneumoniae, a common form of bacteria that lacks a cell wall, to help it release therapeutic chemicals that fight illness while also avoiding detection by the human immune system. Other benefits of utilizing M. pneumoniae as a vector include its minimal chance of developing new abilities and its inability to spread any of its transformed genes to other adjacent organisms.

M. pneumoniae was first altered to make it non-pathogenic. Further adjustments resulted in the production of two enzymes that disintegrate biofilms and assault the bacteria contained within their cell walls. The bacteria was also engineered to secrete antibiotic enzymes more efficiently, according to the researchers.

Because M. pneumoniae is naturally adapted to the lungs, the researchers plan to utilize the modified bacterium to treat biofilms that form around breathing tubes. "Our technology, which is based on synthetic biology and live biotherapeutics, has been developed to meet all safety and efficacy requirements for use in the lungs, with respiratory disorders being one of the primary areas of focus. Our next task will be to address large-scale production and manufacturing, and clinical trials are expected to begin in 2023 "explains Mara Lluch, co-corresponding author of the study and Pulmobiotics' Chief Science Officer.

Other diseases could benefit from the changed bacteria in the long run. "Because bacteria can transport any therapeutic protein to treat the source of a disease, they are perfect vehicles for 'living medicine.' Bacterial vectors provide constant and localised synthesis of the therapeutic chemical once they reach their destination, which is one of the technology's major advantages. Our bacterium, like any other vehicle, can be modified to carry different payloads that target different diseases, with further uses in the future "Luis Serrano, Director of the CRG and co-author of the work, is an ICREA Research Professor.

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