The next pandemic could be caused by fungi that we are powerless against

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⇧ [VIDÉO] You may also like this partner content (after the announcement) As the COVID-19 pandemic is far from over and an outbreak of monkeypox is spreading around the world, worrying leaders of affected countries, epidemiologists fear another threat, microscopic fungi. The latter could cause a new pandemic much more frightening than those caused by viruses, given the little knowledge we have about them and their ability to adapt to our weak therapeutic measures. Despite their presence by our side for a long time, scientists believe that they currently represent a real public health challenge in the face of strong selective pressures, climate change and an ever-growing human population. Only 120,000 of the approximately five million species of fungi have been identified; of these, only a few hundred are known to harm humans. But environmental and climate changes, as well as the excessive use of fungicides in agriculture, have contributed to the creation of infectious “super agents” capable of escaping our limited therapeutic arsenal. According to GAFFI (Global Fund for Action Against Fungal Infections), in recent years, fungal diseases cause approximately 1.6 million deaths per year and more than one billion people suffer from serious fungal diseases. Tom Chiller, a medical epidemiologist at the U.S. Centers for Disease Control and Prevention (CDC), tells National Geographic: “What worries us continuously in the fungal world is the potential of fungi to cause human disease. There are many things we don’t even understand.” In fact, microscopic fungi can cause serious disorders and infections, in particular aspergillosis, which has been increasing for several years, and which raises new questions for the scientific community. It includes Aspergillus fumigatus, which thrives in house dust and decaying plant matter. It can cause complications in people with respiratory problems or a weakened immune system. Inhalation of the spores can cause lung and bronchial infections, which can be fatal in some cases. Although infections caused by bacteria are the most common and well-known, the aging population and the increase in the number of immunocompromised people – as a result of the disease, the treatment – has created an unprecedented window of opportunity for microscopic fungi. Thus, antifungals now represent a greater expenditure than antibiotics, and antifungal strategies should, in the coming years, be at the center of many public health strategies. But why be afraid of mushrooms? Too fast evolution and too weak a therapeutic arsenal Although the mutation rate of fungi is generally lower than that of bacteria or viruses, they can evolve at an extremely rapid rate, causing infections that are increasingly difficult to treat with antifungals. Amelia Barber, a microbiologist at the Hans Knöll Institute in Germany, published in 2020 a study on a case of infection in which the fungus Candida glabrata had two particular mutations that allowed it to adapt very well, and quickly , to new environments and become a lot. more virulent The fungus Aspergillus fumigatus, responsible for serious infections in humans. © Getty Images This virulence is what makes invasive fungal infections so dangerous, unlike superficial varieties such as thrush. These mutated, aggressive fungi excrete tissue-destroying toxins, which they can feed on, just as they break down organic matter as part of an ecosystem’s nutrient cycle. They enter a cycle of self-sufficiency, creating the nutrients they need to thrive. Unfortunately, current therapeutic strategies are not very effective. Powerless against this infection, the body can trigger an extreme immune system reaction that is sepsis. It is a life-threatening organ dysfunction resulting from the body’s dysregulated response to infection, the most serious form of which is septic shock. This exacerbated body response affects the functioning of vital organs in an acute manner and can cause long-term functional sequelae. Resistance only makes matters worse: the death rate is 25% higher when an antifungal-resistant pathogen is involved. Extinction of species by fungi, leading to disproportionate antifungal measures In addition to this direct impact on human health, fungal diseases can also damage plants and crops, causing significant losses in agricultural activities and food production. Animal pathogenic fungi threaten bats, amphibians and reptiles with extinction. Not to mention the forests of Europe and North America that have been decimated by Dutch elm disease, a fungus spread by beetles, according to National Geographic. By saturating the vascular system of the trees, the infection deprives them of water until they wither and die. And in wanting to save these crops, we have unleashed a phenomenon of resistance in fungi. In fact, in the face of these infections, the disproportionate use of fungicides, especially azoles, has quadrupled over the past 10 years, Marin Brewer, a plant pathologist at the University of Georgia, told National Geographic. Agricultural fungicides often use similar strategies to their pharmaceutical counterparts, when fungi become immune to one, they also develop resistance to others. Brewer and her colleague, Michelle Momany, recently demonstrated this by testing samples of Aspergillus fumigatus from patients who had never received antifungal treatment. They discovered resistant strains, known until now only in the agricultural world. In the Netherlands, this resistance reaches up to 20% of cases in certain hospitals and the therapeutic strategy there has had to be modified to systematically identify strains before starting treatment or to use amphotericin B as first-line treatment line In France, this figure has never exceeded 2% and does not call into question the use of voriconazole in the first instance or its prophylactic use in certain immunocompromised patients, or whose aspergillosis is chronic. Notably, fungicides, such as azoles, bind to an enzyme involved in the assembly of ergosterol, a molecule related to cholesterol in humans and an important component of the fungal cell membrane. Without it, the membrane leaks and disintegrates, killing the infectious agent. Specifically, fungi thwart current fungicides in two steps. First, they change the shape of the target enzyme so that the drug no longer recognizes it. They then increase production of the enzyme to ensure that enough ergosterol is produced to keep the fungal cells intact. There are currently only three fungicides, and some fungi such as Candida auris are resistant to all three, threatening the entire world. Candida auris, a global threat due to climate change The fungus Candida auris, resistant to antifungal drugs, has been spreading in hospitals around the world for ten years. Left unchecked, it could cause more deaths than cancer. According to the CDC, nearly half of patients who have contracted Candida auris yeast infection so far have died within 90 days. Candida auris was first discovered in Japan in 2009, in the ear of a 70-year-old woman. It seemed harmless then. Then, from 2012, it materialized almost simultaneously on three continents, emerging as a direct consequence of climate change. Then, it was gradually observed independently in different places around the world. The US Centers for Disease Control and Prevention (CDC) has added it to the list of germs that pose an “urgent threat” to health. This fungus has acquired the ability to withstand high temperatures, while adapting to the excessive use of fungicides in agriculture. The mechanism of this adaptation to heat is currently unknown and is the subject of ongoing studies. In the face of these threats, strengthened and systematic monitoring of fungal infections would help control the transmission of these infections. In addition, remarkable progress has been made in the development of fungal vaccines for human use. In animal studies, protection against all medically important mycoses has been achieved by vaccines composed of live attenuated and killed fungi, crude extracts, recombinant subunit formulations, and “nucleic acid” based vaccines. Three vaccines have been tested in humans, demonstrating the feasibility of clinical trials targeting at-risk populations. Although many scientific and logistical hurdles remain, there are reasons to be optimistic about the availability of clinically approved fungal vaccines. Don’t confuse everything, but respect nature and we will live together. Finally, fungi have been around us for thousands of years—in the water, in the trees, in the earth, in the air—on us and inside our bodies. They are often described as the “fifth kingdom of life on Earth”; they are neither plants nor animals, nor microbes nor protozoa. Its spores can survive extreme temperatures, radiation and even outer space. It is not possible to eradicate fungi, if that were possible! They are of great importance in the medical sector. Penicillin, for example, was developed from a fungus. Some elements of mushrooms are essential nutrients that can prevent cancer. In addition to bacteria, fungi are important as decomposers in the soil food web. Their threads, or hyphae, also physically bind soil particles together, which helps water penetrate the soil and increases the soil’s ability to retain it. Last point: mushrooms could help fight pollution. Some species, such as the oyster mushroom, produce enzymes that digest petroleum hydrocarbons. Some can absorb heavy metals like mercury and even digest polyurethane plastics. As Momany concludes for National Geographic, the rapid acquisition of azole resistance in Aspergillus in the Netherlands serves as a cautionary tale: “Aspergillus is not even a plant pathogen, it’s just ubiquitous in soil. But because it was in the environment when crops and flowers were sprayed with azole, the pathogen quickly developed resistance.” Learning to live with the biodiversity of our planet is becoming a more than vital and crucial issue in the face of accelerating climate change, making the threat of new pandemics even greater.
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