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Drilling down on treatment-resistant fungi with molecular machines

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Drilling down on treatment-resistant fungi with molecular machines

Newly developed molecular drills may be able to fight treatment-resistant fungal infections like Candida auris.
Dr_Microbe/iStock via Getty Images

Ana L. Santos, Rice University; Jacob Beckham, Rice University, and James Tour, Rice University

Fungi are present on the skin of around 70% of the population, without causing harm or benefit. Some fungal infections, like athlete’s foot, are minor. Others, like Candida albicans, can be deadly – especially for individuals with weakened immune systems.

Fungal infections are on the rise because of an aging population and an increased prevalence of chronic diseases. At the same time, fungi are becoming more resistant to treatment. As a result, fungal infections could soon become a serious public health threat.

In 2022, the World Health Organization released its first-ever “Fungal Priority Pathogen List,” calling for improved surveillance, public health interventions and the development of new antifungal drugs.

We are an interdisciplinary team of chemists and biologists charting a new path to tackle drug-resistant infections. We are using tiny nanoscale drills that combat harmful pathogens at the molecular level. As the traditional 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 new antifungal drugs, developing them is challenging. First, it is difficult to develop drugs that selectively kill fungi without harming human cells because of their many similarities.

Second, fungi can rapidly develop resistance to multiple antifungal drugs at once when medications are misused or overused. As such, developing antifungal drugs is much less rewarding for drug companies than developing medications for chronic conditions like diabetes and hypertension that require long-term use.

One solution to this problem could lie in a Nobel Prize-winning technology: molecular machines.

Molecular machines are synthetic compounds that rapidly rotate their components at about 3 million times per second when exposed to light. Doctors can use a light-tipped probe to activate these molecular machines to treat internal infections, or a lamp for skin infections. The light starts the machines spinning, and that rotational motion pushes them to drill through and puncture the cell’s membranes and organelles, which results in cell death.

Our group first used this technology to kill cancer cells in 2017. To target the right cells, molecular machines can be linked to specific peptides that bind only to the desired cells, allowing, for instance, the targeting of specific cancer types. Since then, we have used these molecules to kill bacteria, destroy tissue and stimulate muscle contraction. These properties make molecular machines an enticing candidate technology to address the growing fungal threat.

A diagram showing the structure of a molecular machine as gray lines connected in the shape of several hexagons
The 3D structure of a molecular machine. The molecular machine consists of rotor (top) and stator (bottom) portions connected by a central axle. Following light activation, molecular machines rotate rapidly, drilling into fungal cells.
Tour Lab, Rice University

Testing antifungal molecular machines

Researchers first tested the ability of light-activated molecular machines to kill fungi in Candida albicans. This yeastlike fungus can cause life-threatening infections in immunocompromised people. Compared with conventional drugs, molecular machines killed C. albicans much faster.

Subsequent studies found that molecular machines could also kill other fungi, including molds like Aspergillus fumigatus and species of dermatophytes, the types of fungi that cause skin, scalp and nail infections. Molecular machines even eliminated fungal biofilms, which are slimy, antimicrobial-resistant communities of microorganisms that stick together on surfaces and commonly cause medical device-associated infections.

Unlike conventional antifungals, which target the fungal cell membrane or cell wall, molecular machines localize to the fungal mitochondria. Often referred to as the “powerhouses of the cell,” mitochondria produce energy to power other cellular activities. When activated with visible light, molecular machines destroy the fungal mitochondria. Once the 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 is shrunken following treatment with light-activated molecular machines.
Candida albicans before and after being exposed to light-activated molecular machines. Molecular machines puncture C. albicans‘ cell wall and intracellular organelles, eventually killing the fungal cell.
Matthew Meyer/Rice University.

At the same time, molecular machines also disrupt the tiny pumps that remove antifungal agents from the cell, thus preventing the cell from fighting back. Because these molecular machines act by a mechanical instead of a chemical mechanism, fungi are unlikely to develop defenses against this treatment.

In lab experiments, combining light-activated molecular machines with conventional antifungal drugs also reduced the amount of fungi in C. albicans-infected worms and in pig nails infected with Trichophyton rubrum, the most common cause of athlete’s foot.

New frontiers for fighting fungal infections

These results suggest that combining molecular machines with conventional antifungals can improve existing therapies and provide new options for treating resistant fungal strains. This strategy could also help reduce the side effects of traditional antifungals, such as gastrointestinal upset and skin reactions.

Fungal infection rates will likely continue to rise. As such, the need for new treatments will only become more urgent. Climate change is already causing new human pathogenic fungi to emerge and spread, including Candida auris. C. auris is often resistant to treatment and spread rapidly in health care facilities during the COVID-19 pandemic. According to the Centers for Disease Control and Prevention, strained health care systems, overuse of immunosuppressants and misuse of antibiotics have all been implicated in outbreaks of C. auris.

In the future, researchers could use artificial intelligence to create better antifungal molecular machines. By using AI to predict how different molecular machines will interact with fungi and human cells, we can develop safer and more effective antifungal molecules that specifically kill fungi without harming healthy cells.

Antifungal molecular machines are still in the early stages of development and are not yet available for routine clinical use. However, continuing research gives hope that these machines could one day provide better treatments for fungal infections and other infectious diseases.The Conversation

Ana L. Santos, Postdoctoral Fellow in Microbiology, Rice University; Jacob Beckham, Graduate Student in Chemistry, Rice University, and James Tour, Professor of Chemistry, Rice University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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Out-of-balance bacteria is linked to multiple sclerosis − the ratio can predict severity of disease

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theconversation.com – Ashutosh Mangalam, Associate Professor of Pathology, University of Iowa – 2025-03-03 14:03:00

Out-of-balance bacteria is linked to multiple sclerosis − the ratio can predict severity of disease

The myelin sheaths insulating neurons are damaged in multiple sclerosis.
Steve Gschmeissner/Science Photo Library/Brand X Pictures via Getty Images

Ashutosh Mangalam, University of Iowa

Multiple sclerosis is a disease that results when the immune system mistakenly attacks the brain and spinal cord. It affects nearly one million people in the U.S. and over 2.8 million worldwide. While genetics play a role in the risk of developing multiple sclerosis, environmental factors such as diet, infectious disease and gut health are major contributors.

The environment plays a key role in determining who develops multiple sclerosis, and this is evident from twin studies. Among identical twins who share 100% of their genes, one twin has a roughly 25% chance of developing MS if the other twin has the disease. For fraternal twins who share 50% of their genes, this rate drops to around 2%.

Scientists have long suspected that gut bacteria may influence a person’s risk of developing multiple sclerosis. But studies so far have had inconsistent findings.

To address these inconsistencies, my colleagues and I used what researchers call a bedside-to-bench-to-bedside approach: starting with samples from patients with multiple sclerosis, conducting lab experiments on these samples, then confirming our findings in patients.

In our newly published research, we found that the ratio of two bacteria in the gut can predict multiple sclerosis severity in patients, highlighting the importance of the microbiome and gut health in this disease.

Microscopy image of large clump of rod-like bacteria
Akkermansia is commonly found in the human gut microbiome.
Zhang et al/Microbial Biotechnology, CC BY-SA

Bedside to bench

First, we analyzed the chemical and bacterial gut composition of patients with multiple sclerosis, confirming that they had gut inflammation and different types of gut bacteria compared with people without multiple sclerosis.

Specifically, we showed that a group of bacteria called Blautia was more common in multiple sclerosis patients, while Prevotella, a bacterial species consistently linked to a healthy gut, was found in lower amounts.

In a separate experiment in mice, we observed that the balance between two gut bacteria, Bifidobacterium and Akkermansia, was critical in distinguishing mice with or without multiple sclerosis-like disease. Mice with multiple sclerosis-like symptoms had increased levels of Akkermansia and decreased levels of Bifidobacterium in their stool or gut lining.

Bench to bedside

To explore this further, we treated mice with antibiotics to remove all their gut bacteria. Then, we gave either Blautia, which was higher in multiple sclerosis patients; Prevotella, which was more common in healthy patients; or a control bacteria, Phocaeicola, which is found in patients with and without multiple sclerosis. We found that mice with Blautia developed more gut inflammation and worse multiple sclerosis-like symptoms.

Even before symptoms appeared, these mice had low levels of Bifidobacterium and high levels of Akkermansia. This suggested that an imbalance between these two bacteria might not just be a sign of disease, but could actually predict how severe it will be.

We then examined whether this same imbalance appeared in people. We measured the ratio of Bifidobacterium adolescentis and Akkermansia muciniphila in samples from multiple sclerosis patients in Iowa and participants in a study spanning the U.S., Latin America and Europe.

Our findings were consistent: Patients with multiple sclerosis had a lower ratio of Bifidobacterium to Akkermansia. This imbalance was not only linked to having multiple sclerosis but also with worse disability, making it a stronger predictor of disease severity than any single type of bacteria alone.

Microscopy image of clusters of rod bacteria
Bifidobacterium both produces and consumes mucin, a glycoprotein that protects the gut lining.
Paola Mattarelli and Monica Modesto/Katz Lab via Flickr, CC BY-NC

How ‘good’ bacteria can become harmful

One of the most interesting findings from our study was that normally beneficial bacteria can turn harmful in multiple sclerosis. Akkermansia is usually considered a helpful bacterium, but it became problematic in patients with multiple sclerosis.

A previous study in mice showed a similar pattern: Mice with severe disease had a lower Bifidobacterium-to-Akkermansia ratio. In that study, mice fed a diet rich in phytoestrogens – chemicals structurally similar to human estrogen that need to be broken down by bacteria for beneficial health effects – developed milder disease than those on a diet without phytoestrogens. Previously we have shown that people with multiple sclerosis lack gut bacteria that can metabolize phytoestrogen.

Although the precise mechanisms behind the link between the Bifidobacterium-to- Akkermansia ratio and multiple sclerosis is unknown, researchers have a theory. Both types of bacteria consume mucin, a substance that protects the gut lining. However, Bifidobacterium both eats and produces mucin, while Akkermansia only consumes it. When Bifidobacterium levels drop, such as during inflammation, Akkermansia overconsumes mucin and weakens the gut lining. This process can trigger more inflammation and potentially contribute to the progression of multiple sclerosis.

Our finding that the Bifidobacterium-to-Akkermansia ratio may be a key marker for multiple sclerosis severity could help improve diagnosis and treatment. It also highlights how losing beneficial gut bacteria can allow other gut bacteria to become harmful, though it is unclear whether changing levels of certain microbes can affect multiple sclerosis.

While more research can help clarify the link between the gut microbiome and multiple sclerosis, these findings offer a promising new direction for understanding and treating this disease.The Conversation

Ashutosh Mangalam, Associate Professor of Pathology, University of Iowa

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How are clouds’ shapes made? A scientist explains the different cloud types and how they help forecast weather

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theconversation.com – Ross Lazear, Instructor in Atmospheric and Environmental Sciences, University at Albany, State University of New York – 2025-03-03 07:18:00

Lenticular clouds, like this one over a mountain in Chile, can look like flying saucers.
Bilderbuch/Design Pics Editorial/Universal Images Group via Getty Images

Ross Lazear, University at Albany, State University of New York

Curious Kids is a series for children of all ages. If you have a question you’d like an expert to answer, send it to curiouskidsus@theconversation.com.


How are clouds’ shapes made? – Amanda, age 5, Chile


I’m a meteorologist, and I’ve been fascinated by weather since I was 8 years old. I grew up in Minnesota, where the weather changes from wind-whipping blizzards in winter to severe thunderstorms – sometimes with tornadoes – in the summer. So, it’s not all that surprising that I’ve spent most of my life looking at clouds.

All clouds form as a result of saturation – that’s when the air contains so much water vapor that it begins producing liquid or ice.

Once you understand how certain clouds develop their shapes, you can learn to forecast the weather.

A view showing typical cloud heights shows tall cumulonimbus clouds, low level cumulus and high-level cirrus.
Cloud types show their general heights.
Australian Bureau of Meteorology

Cotton ball cumulus clouds

Clouds that look like cartoon cotton balls or cauliflower are made up of tiny liquid water droplets and are called cumulus clouds.

Often, these are fair-weather clouds that form when the Sun warms the ground and the warm air rises. You’ll often see them on humid summer days.

A horse or donkey next to river bank with puffy clouds in the sky.
Cumulus clouds over Lander, Wyo.
Ross Lazear, CC BY-ND

However, if the air is particularly warm and humid, and the atmosphere above is much colder, cumulus clouds can rapidly grow vertically into cumulonimbus. When the edges of these clouds look especially crisp, it’s a sign that heavy rain or snow may be imminent.

Wispy cirrus are ice clouds

When cumulonimbus clouds grow high enough into the atmosphere, the temperature becomes cold enough for ice clouds, or cirrus, to form.

Clouds made up entirely of ice are usually more transparent. In some cases, you can see the Sun or Moon through them.

Streaks of high white clouds look like paintbrush strokes
Cirrus clouds over the roof of Bard College in Annandale-on-Hudson, N.Y.
Ross Lazear, CC BY-ND

Cirrus clouds that forms atop a thunderstorm spread outward and can form anvil clouds. These clouds flatten on top as they reach the stratosphere, where the atmosphere begins to warm with height.

However, most cirrus clouds aren’t associated with storms at all. There are many ice clouds associated with tranquil weather that are simply regions of the atmosphere with more moisture but not precipitation.

Fog and stratus clouds

Clouds are a result of saturation, but saturated air can also exist at ground level. When this occurs, we call it fog.

In temperatures below freezing, fog can actually deposit ice onto objects at or near the ground, called rime ice.

YouTube video
Reading clouds, with the National Oceanic and Atmospheric Administration.

When clouds form thick layers, we add the word “stratus,” or “layer,” to the name. Stratus can occur just above the ground, or a bit higher up – we call it altostratus then. It can occur even higher and become cirrostratus, or a layer or ice clouds.

If there’s enough moisture and lift, stratus clouds can create rain or snow. These are nimbostratus.

How mountains can create their own clouds

There are a number of other unique and beautiful cloud types that can form as air rises over mountain slopes and other topography.

Lenticular clouds, for example, can look like flying saucers hovering just above, or near, mountaintops. Lenticular clouds can actually form far from mountains, as wind over a mountain range creates an effect like ripples in a pond.

A cloud appears to stream off the side of a tall mountain peak.
A banner cloud appears to stream out from the Matterhorn, in the Alps on the border between Italy and Switzerland.
Zacharie Grossen via Wikimedia, CC BY

Rarer are banner clouds, which form from horizontally spinning air on one side of a mountain.

Wind plays a big role

You might have looked up at the sky and noticed one layer of clouds moving in a different direction from another. Clouds move along with the wind, so what you’re seeing is the wind changing direction with height.

Cirrus clouds at the level of the jet stream – often about 6 miles (10 kilometers), above the ground – can sometimes move at over 200 miles per hour (320 kilometers per hour). But because they are so high up, it’s often hard to tell how fast they are moving.


Hello, curious kids! Do you have a question you’d like an expert to answer? Ask an adult to send your question to CuriousKidsUS@theconversation.com. Please tell us your name, age and the city where you live.

And since curiosity has no age limit – adults, let us know what you’re wondering, too. We won’t be able to answer every question, but we will do our best.The Conversation

Ross Lazear, Instructor in Atmospheric and Environmental Sciences, University at Albany, State University of New York

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Who’s who at the Vatican?

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theconversation.com – Daniel Speed Thompson, Associate Professor of Religious Studies, University of Dayton – 2025-03-03 07:18:00

Who’s who at the Vatican?

Deacons take part in a mass in St. Peter’s Basilica that was supposed to be presided over by Pope Francis.
AP Photo/Alessandra Tarantino

Daniel Speed Thompson, University of Dayton

For more than two weeks, eyes have been on the Vatican, awaiting news about Pope Francis’ health. The pope has been at Rome’s Gemelli Hospital since Feb. 14, 2025, being treated for double pneumonia and other complications.

When a pope is ill, resigns or passes away, who steps in? And who else helps lead the Holy See? The Conversation U.S. asked Daniel Speed Thompson, a theologian at the University of Dayton, for some insight into Vatican City.

Who are the most powerful people at the Vatican, besides the pope?

The Vatican houses the central government of the Catholic Church and is also an independent city-state. The pope is both the head of the Catholic Church and head of state.

In order to govern both, he has the Roman Curia, meaning “court.” In modern terms, the Curia is the papal bureaucracy. It is an extension of the pope’s authority.

In Catholic doctrine, the pope has the highest authority in the church. He can exercise it alone or with the College of Bishops, made up of all the bishops in the world. Bishops named by the pope to the office of “cardinal” can, if under 80 years old, vote to elect a new pope. Some cardinals, but by no means all, serve in the papal Curia in Rome.

Besides the pope, curial officials who oversee important aspects of the church’s political and religious life are often powerful figures. For example, the secretariat of state, headed by Cardinal Pietro Parolin, oversees relations with other countries and international organizations. It also oversees the Vatican’s diplomatic corps.

Two men in black robes with red skullcaps and red sashes walk on a paved road, flanking a man in white robes.
Pope Francis smiles as he walks alongside Vatican Secretary of State Pietro Parolin, left, and Cardinal Giuseppe Versaldi at the Vatican in 2014.
AP Photo/Gregorio Borgia

The Dicastery – “department” – for the Doctrine of the Faith, led by Cardinal Víctor Manuel Fernández, addresses questions about correct Catholic teaching on faith and morals. The Dicastery of Bishops, headed by Cardinal Robert Prevost, coordinates the nominations of new bishops around the world.

All these officials work under the authority of the pope, advocating for and implementing his agenda. For example, Prevost has suggested that all Catholics should be involved in the selection of bishops. This idea is linked with Francis’ call for a more “synodal” church: one that is less hierarchical and shaped by lay Catholics’ concerns and challenges.

If a pope can’t fulfill his duties, who steps in?

When a pope dies – or resigns, like Benedict XVI did in 2013 – the governance of the Catholic Church formally falls to the College of Cardinals. However, the authority of the college is very limited. On their own, cardinals cannot make any significant decisions concerning faith, morals and worship. Nor can they undo previous papal decisions or change church laws about electing a new pope.

All the heads of the dicasteries lose their office upon the death or resignation of a pope. The College of Cardinals serves as a caretaker government whose primary purpose is to prepare for the election of the new pope and oversee day-to-day workings of the Vatican.

One cardinal, known as the “camerlengo,” is responsible for confirming the pope’s death or resignation. He then assumes control over the pope’s residence and coordinates the funeral, if needed. The camerlengo also takes custody of the Vatican’s property in Rome and supervises details for the upcoming conclave.

A man wearing a priest's collar gestures as he speaks, sitting in front of a framed portrait of Pope Francis.
Cardinal Camerlengo Kevin Farrell talks with The Associated Press in his office in Rome in 2018.
AP Photo/Paolo Santalucia

The day-to-day business of the Catholic Church continues, but no big decisions can be made in the absence of a pope. The church cannot appoint new bishops, and the Vatican cannot start new diplomatic efforts.

Are officials at the Vatican often nominated to be pope?

Sometimes. Francis was a cardinal from Argentina before his election as pope and had not served in the Roman Curia. However, Benedict XVI, Francis’ predecessor, did serve as the prefect of the Congregation – now called Dicastery – for the Doctrine of the Faith. Some recent popes served in the Curia earlier in their career but not immediately before their election.

What do you wish more people understood about the Vatican?

Three things. First, the Vatican is unlike any organization in the world. Its religious mission and political status rest on nearly 2,000 years of history. This complicated story provides a unique tradition that anchors the institution of the Catholic Church, but can also block the church from critical self-examination and renewal.

Second, the Vatican is like every organization in the world. Vatican officials can be faithful to the highest standards of their religion, truly wishing to serve the church and the common good of humanity. But they can also be flagrantly immoral, even criminals, and careerist seekers of status or luxury. Francis has consistently called out priests and bishops who see themselves as somehow superior by virtue of their office or their ordination.

Finally, compared with the massive bureaucracies of modern governments and corporations, the Vatican is relatively small and not as wealthy as it is often portrayed.

Although the Curia manages a vast international organization, its resources are far closer to my own midsize Catholic university than to the U.S. government or Apple. Vatican City and the Holy See employ about 2,000 people, with an operating budget of about US$835 million.

Yes, the Catholic Church has wealth – and the ongoing problem of deficits and financial corruption. But the Vatican’s resources pale in comparison with what a modern state or large company can muster.The Conversation

Daniel Speed Thompson, Associate Professor of Religious Studies, University of Dayton

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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