New research has shown that if antibiotics are administered with an enzyme called endolysin, the combined effect protects against infection by bacterial resistance in all bodily organs.
Two important classes of antibiotics are beta-lactams (e.g. penicillin) and macrolides (e.g. erythromycin), which are used to treat life-threatening infections such as meningitis. The fact that the bacteria that cause the disease are becoming resistant is a grave concern, as the patients who have the disease risk permanent brain and neurological damage.
“There are two main problems in meningitis – the difficulty antibiotics have crossing the blood-brain barrier and the increase in bacterial resistance,” explained principal investigator Federico Iovino, associate professor and research group leader at the Department of Neuroscience, Karolinska Institutet.
“Our results show that with the supplementation of endolysins, we can restore the effectiveness of antibiotics, even when the bacteria are resistant.”
Protecting human cells from bacterial resistance
The protein endolysin is an enzyme derived from a bacteriophage virus, which kills bacteria by breaking down the bacterial cell.
In the laboratory, the researchers found that an endolysin called cpl-1 protects human cells from blood and cerebrospinal fluid when exposed to Streptococcus pneumoniae (the pneumococcus), resistant to penicillin or erythromycin. These pneumococci are the primary cause of meningitis globally. Researchers have successfully experimented with endolysin combined with penicillin or erythromycin.
Niels Vander Elst, postdoctoral researcher in Federico Iovino’s group, said: “The combination protected nerve cells from bacterial resistance by resistant pneumococcal strains which have affected patients and which we have obtained from Swedish hospitals.”
Antibiotics quickly enter the brain
The researchers then used an animal model for meningitis in which mice were infected with penicillin-resistant pneumococci. While endolysin alone protected against infection, penicillin alone did not.
When the mice received a combination of antibiotics and endolysin, they were protected against disease, and the antibiotics recovered their effectiveness.
Dr Iovino said: “It takes time for antibiotics to get past the blood-brain barrier, upwards of several days, but endolysin can enter the brain very quickly within a few hours.
“Its speed is a unique property that’s important since brain neurons start to get damaged as soon as the bacteria are present. It also has another important advantage – it doesn’t give the bacteria time to develop resistance.”
Further tests on other resistant bacteria
The researchers now intend to study the effectiveness of endolysin with other types of resistant bacteria so that it can be used as a powerful weapon against the bacterial resistance that causes serious diseases, including meningitis.
“For the first time, we’ve shown that endolysin is effective against the bacteria that cause meningitis,” Dr Iovino concluded.
“Our data also bridges earlier gaps in our knowledge by showing that they can pass through the blood-brain barrier and help antibiotics to recover their effectiveness against bacterial resistance.”
