EXPO 40 years BCCM: Natural healers

Staphylococcus epidermidis (LMG 10273)

In February 2018, a group of researchers from the University of California discovered that the bacterium Staphylococcus epidermidis has cancer-fighting powers. This bacterium is commonly found in and on healthy human skin. After careful analysis, scientists noted that S. epidermidis produces a chemical compound (6-N-hydroxyaminopurine) that resembles a certain DNA component. When the researchers tested the compound (6-HAP for short) in the laboratory, it was found to stop DNA production. Specifically, the chemical prevented cancer cells from multiplying further.

Omega 3-fatty acids

It is an indisputable fact that omega 3-fatty acids are essential for our survival. Currently, the sources of these polyunsaturated fatty acids used for human consumption are often oily fishes such as herring, mackerel, sardines and tuna. Due to the increasingly growing human population and the drastically decreasing amount of the abovementioned fish stocks, these presently used sources of omega 3-fatty acids may become too scarce to provide enough essential fats for humans and thus impede future human survival. The production of microalgae, the original producers of omega 3-fatty acids such as EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), may help solve this problem. Using microalgae as a direct source of omega 3 instead of the classic fish oils could provide us with a more sustainable alternative and also lead to more healthy fish stocks for following human generations.

Towards the Industrial Production of Omega-3 Long Chain Polyunsaturated Fatty Acids from a Genetically Modified Diatom Phaeodactylum tricornutum. Hamilton et al., PLOS ONE (2015)

Sustainable production of eicosapentaenoic acid-rich oil from microalgae: Towards an algal biorefinery. Sivakumar et al., Journal of Applied Microbiology (2022)

Omega-3 fatty acids of microalgae as a food supplement: A review of exogenous factors for production enhancement. Perdana et al., Algal Research (2021)

Origin of Marine Fatty Acids. I. Analyses of the Fatty Acids Produced by the Diatom Skeletonema costatum. Ackman et al., Journal of the Fisheries Research Board of Canada (1964)

Spirulina

Spirulina (Arthrospira) is a cyanobacteria that has been consumed for centuries due to its rich nutritional profile and potential health benefits. As an example, there are reports of the consumption of Spirulina, harvested from Lake Texcoco, and prepared as dried cake by the Aztecs, since around 1,300 ago.

Today, the use of this microorganism is widespread, being one of the most cultivated microalgae in the world.

Spirulina is primarily grown as a feedstock for protein, which constitute around 60% of its mass, which is the highest compared with the other sources of protein. It is also rich in vitamins, minerals, and other bioactive compounds such as β-carotene and zeaxanthin, making it a popular dietary supplement for individuals looking to support their overall health and wellness. It is also a supplement for vegetarians and vegans.

Spirulina as food can be easily absorbed in the human body and the safe recommended dosage is approximately 3-10 g/d for adults, with 30 g/d being the maximum limit.

This cyanobacterium contains several compounds that have been shown to support immune system function and that have prebiotic and antioxidant effects.

If you want to try it, Spirulina, as functional foods, can be found in powder, biscuits, cookies, baby food formulas, chocolates, yoghurt, beverages, smoothie, candies etc.

Mycobacterium bovis

M. bovis is a member of the M. tuberculosis complex (MTBC) that prefers animal hosts like cattle, with possible zoonotic spillover to humans. Symptoms of bovine tuberculosis include fever, night sweats, weight loss, fatigue, and a persistent cough. Thanks to the invention of pasteurization - the simple yet effective process of heating - the risk of M. bovis infection by consuming raw milk or dairy products from infected cattle has lowered significantly. An attenuated strain of M. bovis, M. bovis BCG (Bacille Calmette-Guérin), is used as a vaccine in many high-burden countries to protect against acquiring TB, though its efficacy is questionable.

Immunotherapy

The Bacillus Calmette-Guérin (BCG) vaccine is a widely used immunotherapy for the treatment of bladder cancer. Originally developed as a vaccine against tuberculosis, BCG has shown remarkable efficacy in the treatment of non-muscle invasive bladder cancer (NMIBC). When administered directly into the bladder, BCG stimulates a potent immune response against cancer cells, leading to tumor regression and prevention of disease recurrence. BCG is composed of live attenuated strains of Mycobacterium bovis, a bacterium related to tuberculosis in cattle. By stimulating the immune system, BCG activates various immune cells, such as T cells and natural killer cells, which help in targeting and destroying cancer cells within the bladder. The exact mechanisms by which BCG exerts its anti-cancer effects are still being investigated, but it is believed that the vaccine induces both a local immune response in the bladder and a systemic immune response throughout the body. BCG treatment has become a standard therapy for NMIBC, significantly reducing the risk of disease progression and improving patient outcomes.

BCG Pasteur 1721 vaccine strain (Master et al, 2008) has been transferred from VIB-UGent to the BCCM/ITM Mycobacteria Collection situated at the Institute of Tropical Medicine in Antwerp.

The discovery of penicillin

Alexander Fleming was a British microbiologist who studied bacterial pathogens. One day, a Staphylococcus culture from his laboratory was infected by a fungus, which was found to inhibit the growth of the bacteria. He understood that the fungus, a Penicillium, produced a compound that had antibacterial activity. Almost by accident, the first antibiotic called penicillin was discovered. We are in 1928. In the following years, A. Fleming tried to isolate the compound, but without success. In the late 1930s and early 1940s, Howard Florey and Ernst Chain resumed Fleming's work and succeeded in purifying penicillin. They also conducted the first clinical trials and developed the large-scale production of the antibiotic. The latter could be distributed to US GIs landing on European shores in 1944, giving them an advantage against enemy armies. In 1945, A. Fleming, H. Florey and E. Chain won the Nobel Prize in Medicine.

The discovery and development of penicillin. Commemorative booklet (1999)

Microscopic fungi as a source of pharmaceutical drugs

Since the discovery of penicillin in 1928, other pharmaceutical compounds have been developed from various fungi. Cephalosporins, another family of antibiotics, were isolated from Cephalosporium acremonium in the 1950s. More recently, a new class of antifungal drugs, the echinocandins, were inspired by natural metabolites from various fungal species. In 1983, cyclosporines were launched on the market. Synthesised by Tolypocladium inflatum, they were the first immunosuppressive treatment and revolutionised allogeneic organ transplants. Statins are another example. They are produced by several Aspergillus and Penicillium species and are used to lower blood cholesterol levels.

Phage therapy

Some pathogens have developed a resistance to many antibiotics. For such extreme cases, another natural enemy of bacteria can help us: phages, viruses that kill bacteria.

Lytic phages will recognise their target bacteria and infect them. During this infection, the phage will use the bacterial cell processes for its own gain, turning the bacteria into phage-producing factories. Eventually, the bacterial cells will fall apart, releasing the newly created phages, which can in turn infect other bacteria. 

Phage therapy holds several advantages over classical medication:

• Phages target a very specific bacterial host, which makes that therapeutic phages would not interfere with our own body cells or with our gastro-intestinal flora. This high specificity is at the same time a limiting factor, since combatting a specific infection requires the right phage.
• Phage therapy is not influenced by resistance mechanisms, contrary to antibiotic treatments.
• Phages use their host for amplification, meaning that in theory, a single dose could be enough to eliminate any bacterial infection.

Despite these apparent advantages, bacteriophage therapy is currently restricted to severe bacterial infections such as sepsis and cystic fibrosis, if no alternative standard treatment is available. More translational research is needed regarding administration, dosage and potential side effects before phage therapy might be considerd a standard treatment.

Phage Therapy in the Resistance Era: Where Do We Stand and Where Are We Going? Luong et al., Clinical therapeutics (2020).

Production of medication and vaccines

While antibiotics are naturally produced by some fungi, micro-organisms can also be modified through the use of plasmids in order to produce a variety of medicinal products. Plasmids enable the introduction of foreign genes into the microbial genome, and the expression of therapeutic proteins (biologicals) such as cytokines, antibodies, insulin, growth factors, and clotting factors, that can be purified for medical use. This process has led to the production of effective treatments for many medical conditions, improving the health and quality of life for millions of people worldwide. Additionally, plasmids are being used for the production of DNA vaccines and mRNA vaccines, the creation of antibody-producing animal cell lines, and in gene therapies.