The incidence of fungal infections is rising due to factors such as the aging population, widespread use of antibiotics and possibly even global warming.
Most people will experience a fungal infection at least once in their lifetime, but today’s oral antifungal medications don’t always work well and come with a spectrum of negative side effects ranging from headaches and rash to liver and kidney toxicities.
Now, researchers from the Technion-Israel Institute of Technology’s Faculty of Biotechnology and Food Engineering reveal in the journal Advanced Functional Materials that they successfully cured fungal infections in mice using a soil-dwelling bacterium.
The target fungus in the study was Candida, a type of yeast that is one of the primary sources of fungal infections. Candida resides in most people’s bodies harmlessly, but it can grow out of control under certain conditions. The researchers in Haifa found that bacteria called Bacillus subtilis naturally produces and secretes substances that inhibit Candida growth.
“Our first challenge was to develop a transport system that would enable application of the live bacteria on the infected lesion without impairing their ability to proliferate and secrete their therapeutic substances in the target site,” said lead researcher Assistant Professor Boaz Mizrahi, who also is a member of the Technion’s Russell Berrie Nanotechnology Institute and Lorry I. Lokey Interdisciplinary Center for Life Sciences and Engineering.
Ayelet Shabtay-Orbach, a staff member of the Technion’s Laboratory for Biomaterials, and graduate student Maayan Lupton developed the bacterium into a unique thermo-responsive gel that is in liquid form in the refrigerator and at room temperature (enabling easy application on the skin), but hardens within seconds after being applied to the skin.
The gel not only contains thermo-responsive polymers but also food substances meant to maintain the life of the bacteria on the skin, so that they continue producing antifungal agents to treat the infection.
Rapid skin healing
After marking the bacteria-laced gel with a fluorescent substance to allow them to monitor its progress visually, the researchers applied the gel on the skin of lab mice suffering from a fungal infection. The formulation penetrated deep into the skin but not into the underlying blood vessels, implying that the effect of the formula is limited to the diseased area.
Later, the clinical efficacy of the bacterial formulation was demonstrated on mice suffering from Candida infection. In the control groups – treated with bacteria-free gel or not treated at all – the infection continued to develop, but the group treated with the bacterial gel showed rapid skin healing.
Moreover, comparison of the novel treatment to the commonly used topical antifungal drug ketoconazole demonstrated the superiority of the Technion’s gel both from the clinical and the safety perspectives.
The researchers noted that aside from development of the unique gel, a new therapeutic treatment model was demonstrated in their experiments.
The bacterial gel acted like a minuscule, localized factory producing the active substance after penetrating the target infection. This is in contrast to the standard pharmaceutical model, in which the drug passes through the entire body and portions of it may be broken down in the process.
The Technion scientists said they anticipate that their novel model can be used in the future to treat a range of diseases, including psoriasis, acne, various inflammations and even cancer.
“This platform may enable rational design of novel formulations composed of secreting bacteria inside a responsive, smart, hydrogel—which is the prerequisite for producing a successful drug delivery system,” they wrote.
In addition to the team of scientists and students from the Technion, three researchers from the department of molecular microbiology and biotechnology at Tel Aviv University participated in the study.