Patients afflicted by cystic fibrosis, a hereditary disease, often suffer from obstinate infections by the Pseudomonas aeruginosa bacterium. This germ forms so-called biofilms in the lung. This layer of mucus allows them to defy the treatment with antibiotics. Scientists of the Helmholtz Centre for Infection Research (HZI) in Braunschweig recently tested combinations of several antibiotics which turned out to be effective despite this protection. This was made possible by a new model the researchers developed and which they just presented in "Antimicrobial Agents and Chemotherapy".
Upper airway infections, usually elicited by Pseudomonas aeruginosa, are the most common cause of death in people afflicted by cystic fibrosis. Since this germ surrounds itself with a layer of mucus it is very difficult to treat. In contrast, bacteria that are unable to produce a biofilm are more susceptible to antibiotics. "Previously, we were able to investigate biofilms in the laboratory only in very artificial models," says Dr Vinay Pawar, who is a scientist of the "Molecular Immunology" department of the HZI and the lead author of the publication. Together with his colleagues from the "Molecular Bacteriology" department, he just succeeded to establish a new model system in mice. "It resembles the situation in man very closely."
This model allows the researchers for the first time to realistically simulate the formation of the bacterial biofilm and thus to trace what makes the germs so resistant to medications. But their first finding was that the agents, tobramycin, ciprofloxacin and colistin, cannot harm the biofilm bacteria at normal dosage. Only a strongly increased dose showed an effect. But this dose level would also increase the adverse effects in patients.
In order to bypass this, the researchers combined two of the antibiotics and were successful: "The combination of tobramycin and colistin is highly effective against pseudomonas," says Pawar. The two agents use different mechanisms of actions and therefore complement each other optimally in the fight against the Biofilm bacteria.
The germs in the outer region of this bacterial community have a very active metabolism and proliferate at a high rate. This is where tobramycin is effective. It prevents the bacteria from producing proteins. In the absence of these vital components, the cells of the microbes die. In contrast, colistin attacks the cell wall, which allows its to also kill the less active bacteria that are common on the inside of the biofilm.
Using the Pseudomonas Infection as an example, the researcher were able to show that their model system allows them to investigate other infections as well. This includes mixed populations. "Usually, several different types of bacteria live together in a community in biofilms," says Pawar. "Our model allows us to investigate some more realistic conditions than was previously possible." The researchers will use their mouse model in the future to test novel substances, including agents developed at the HZI.
Original publication:
Vinay Pawar, Uliana Komor, Nadine Kasnitz, Piotr Bielecki, Marina C. Pils, Benjamin Gocht, Annette Moter, Manfred Rohde, Siegfried Weiss and Susanne Häussler. In vivo efficacy of antimicrobials against biofilm producing Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2015 Jun 8. DOI:10.1128/AAC.00194-15.
