"The groundwork of all happiness is health." - Leigh Hunt

Drilling down on treatment-resistant fungi with molecular machines

Fungi are present on the skin of about 70% of the population, without harm or profit. Some fungal infections, reminiscent of athlete's foot, are minor. Others, like, could be fatal – especially for people with Weak immune system.

Fungal infections are on the rise. Due to the growing population and increasing prevalence of chronic diseases. At the identical time, fungi are forming More resistant to treatment. As a result, fungal infections can quickly turn out to be a serious public health threat.

In 2022, the World Health Organization announced its first “List of fungal priority pathogens“The call for improved surveillance, public health interventions and development of recent antifungal drugs.

we're one. Interdisciplinary team Of Chemist And Biologists Developing a brand new technique to combat drug-resistant infections. We are using tiny nanoscale molecules that fight harmful pathogens on the molecular level. As the standard antimicrobial research pipeline struggles, our approach has the potential to rejuvenate the fight against these stubborn infections.

Molecular machines as alternative antifungals

While doctors urgently need latest antifungal drugs, Their development is difficult. First, it's difficult to develop drugs that selectively kill the fungus without harming human cells. Many similarities.

Second, fungi can Rapidly develops resistance to multiple antifungal drugs at the same time. When drugs are misused or overdosed. Thus, developing antifungal drugs is far less profitable for drug corporations than developing drugs for chronic conditions reminiscent of diabetes and hypertension that require long-term use.

An answer to this problem could also be in a single. Nobel Prize-winning technology: Molecular Machines

Molecular machines are synthetic compounds that rotate their components at a speed of about 3 million times per second when exposed to light. Doctors can use light probes to activate these molecular machines to treat internal infections, or lamps for skin infections. The light causes the machines to rotate, and this rotational motion causes them to pierce and puncture cell membranes and organelles, resulting in cell death.

Our group used it first This technology to kill cancer cells In 2017 To goal the correct cells, molecular machines could be attached to specific peptides that bind only to the specified cells, for instance, Targeting specific types of cancer. Since then, we have now used these molecules. Kill bacteria, Destroy the tissue And Stimulation of muscle contraction. These properties make molecular machines. Attractive candidate technology To combat the growing threat of fungal.

3D structure of a molecular machine. A molecular machine consists of rotor (top) and stator (bottom) parts connected to a central axle. After the sunshine is activated, the molecular machines spin rapidly, punching holes within the fungal cells.
Tour Lab, Rice University

Probing antifungal molecular machinery

The researchers were the primary to check the power of light-driven molecular machines to kill fungi. It may cause a yeast-like fungus. Life-threatening infection In immunocompromised people. Molecular machines kill much faster than conventional medicine.

Later studies found that the molecular machines could also kill other fungi, including molds and kinds of dermatophytes, the kinds of fungi that cause infections of the skin, scalp and nails. Molecular machines were also abolished. Fungal biofilmthat are thin, antimicrobial-resistant communities of microorganisms that stick together on surfaces and commonly cause infections related to medical devices.

In contrast to Conventional antifungals, which goal the fungal cell membrane or cell wall, molecular machinery localizes to fungal mitochondria. often called “Powerhouses of cellsMitochondria produce energy to power other cellular activities. When activated with visible light, the molecular machines destroy fungal mitochondria. Once a fungal cell's mitochondria stop working, the cell loses its energy supply and dies.

Two black and white electron microscopy images of a fungal cell.  The left image shows a large, round, healthy cell, while the cell on the right has shrunk after treatment with mildly activated molecular machines.
Before and after the emergence of light-driven molecular machines. Molecular machines puncture the cell wall and intracellular organelles, eventually killing the fungal cell.
Matthew Meyer / Rice University.

At the identical time, so do molecular machines Disruption of small pumps which removes antifungal agents from the cell, thereby stopping the cell from fighting back. Because these molecular machines work through mechanical slightly than chemical mechanisms, fungi are unlikely to develop immunity to this treatment.

In laboratory experiments, combining mildly activated molecular machines with traditional antifungal drugs also reduced the quantity of fungus in infected insects and pig nails, probably the most common cause. Player's feet.

New frontiers for fighting fungal infections

These results suggest that combining molecular machines with traditional antifungals may improve existing therapies and supply latest options for the treatment of resistant fungal strains. This strategy may help reduce the unintended effects of conventional antifungals, reminiscent of gastrointestinal upset and skin reactions.

The rate of fungal infections is more likely to increase. Thus, the necessity for brand spanking new treatments will only turn out to be more urgent. Climate change is already causing this. New human pathogenic fungi Emergence and spread, incl . is usually immune to treatment and spreads rapidly in health care facilities. During the COVID-19 pandemic. According to the Centers for Disease Control and Preventionstressed health care systems, overuse of immunosuppressants and misuse of antibiotics have all been implicated within the outbreak.

In the long run, researchers may use Artificial intelligence To create higher antifungal molecular machines. By using AI to predict how different molecular machines will interact with fungi and human cells, we are able to develop safer and simpler antifungal molecules that specifically goal fungi without harming healthy cells. They kill

Antifungal molecular machines are still within the early stages of development and will not be yet available for routine clinical use. However, continued research raises hopes that these machines may sooner or later provide higher treatment for fungal infections and other infectious diseases.