In the course of a new and groundbreaking study led by Dr. Natalia Freund and the doctoral candidate Avia Waston at the Sackler School of Medicine at Tel Aviv University, the research group succeeded in isolating monoclonal antibodies which hindered the growth of tuberculosis germs in laboratory mice.
The antibodies were isolated from a patient who succumbed to an active tuberculosis disease but has since recovered. This was, in fact, the first time in history that researchers have managed to develop a “biological antibiotic” and demonstrate that human monoclonal antibodies can act as a substitute for the traditional chemical antibiotics, and protect mice from a pathogenic bacterial challenge. The study was carried out in a collaboration with two additional laboratories from the US and China and was published in the prestigious scientific journal Nature Communications (Human antibodies targeting a Mycobacterium transporter protein mediate protection against tuberculosis).
For the past century, antibiotics have served as the main treatment against germs, being both efficient and cheap. Antibiotics are chemical agents designed to block and destroy specific cells, such as microbial cells. However, since some biological mechanisms are common to both human and microbial cells, the range of antibiotics that can safely be used without harming the patient is limited. For example, cell wall components of many strains of microbes are common to human cells; therefore, any damage caused to the microbial cell walls can lead to extensive damage to body systems. Furthermore, in recent years, the number of antibiotic-resistant microbial strains is on the increase, which presents new challenges to defending the body from microbes in the post-antibiotic era.
For these reasons, Dr. Natalia Freund and her lab team have spent the recent few years searching for a biological substitute for known antibiotics. Antibodies are proteins that are produced naturally by our immune response following infection or a vaccine. They harbor many advantages such as specificity, stability, and safety. For these reasons, today, antibodies are in widespread use in the treatment of cancer, autoimmune diseases, and viral infections such as COVID-19.
The research team chose as its test model the Tuberculosis, which is caused by the bacilli mycobacterium tuberculosis, and were successful, for the first time in the history of medicine, in devising an effective treatment based on anti-bacterial antibodies naturally developed during infection.
Another reason for the choice of tuberculosis was that although the vaccine against tuberculosis was developed 100 years ago, and is based on the attenuated bacillus bovis (BCG) strain, it is not effective in adults and does not prevent infection. Also, in recent years, more and more varieties of the disease have developed that are resistant to the only treatment that is currently available, namely, treatment with antibiotics. Since tuberculosis germs are very infectious, transferred in the air, and detrimental to the lungs, the spread of resistant strains of tuberculosis that modern medicine cannot combat is a real danger.
Currently, approximately one-quarter of the world’s population is infected with tuberculosis, while the rates of drug-resistant strains of the disease are peaking to as high as 40% in some countries. In Israel, there are about 200 active tuberculosis cases per year.
According to Dr. Freund, “antibiotics are highly efficacious and cost-effective, and therefore for the last 100 years, they have been our only weapon against bacterial infections. Unfortunately, antibiotics have become less and less effective, and in the main cases of drug-resistance physicians are empty-handed in finding an appropriate treatment for their patients. Therefore, new ways to kill bacteria are urgently needed.”
“Advances in biological medicine have enabled us to rout the germs in new ways that are not based solely on antibiotics, and therefore allow a solution to the challenge posed by resistant germs,” Dr. Freund explained, stressing that “our study is an initial proof of concept of employing monoclonal antibodies (derived from single cells) as an effective therapy in combating bacterial pathogens.”
It should be noted that owing to the size and complexity of the tuberculosis bacillus, the isolation of its monoclonal antibodies has been extremely challenging. But now the researchers in Dr. Freund’s lab have succeeded in pinpointing a phosphate pump protein on the bacillus cell wall which supplies energy to the bacterium and is highly specific and conserved to all tuberculosis strains.
The two types of antibodies the researchers have isolated, which block the action of the pump, inhibited the bacteria’s growth, and reduced the bacterial levels by 50% in mice, compared with mice that were not treated with antibodies. Furthermore, these antibodies are active against three different strains of the tuberculosis bacillus and, seeing as the antibodies are directed against the phosphorus pump which is common to all strains of this bacillus, it is expected that the vaccine will be effective against many other strains that were not investigated, including those that are resistant to antibiotics.
Presently, given the success of the study, Dr. Freund’s lab is investigating the possibility of extending the “biological” substitute for antibiotics to include other diseases. “The model that has proven successful in this study will enable us to extend our future work to include other diseases such as pneumonia and staphylococcus infections,” said Dr. Freund.