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How do _Candida auris_ and other fungi develop drug resistance? A microbiologist explains

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How do Candida auris and other fungi develop drug resistance? A microbiologist explains

Candidiasis is a severe fungal infection that can spread easily in medical facilities.
Atlas of Pulmonary Pathology/Flickr, CC BY-SA

Jeffrey Gardner, University of Maryland, Baltimore County

One of the scariest things you can be told when at a doctor's office is “You have an antimicrobial-resistant infection.” That means the bacteria or fungus making you sick can't be easily killed with common antibiotics or antifungals, making treatment more challenging. You might have to take a combination of for weeks to overcome the infection, which could result in more severe side effects.

Unfortunately, this diagnosis is becoming more common around the world.

The yeast Candida auris has recently emerged as a potentially dangerous fungal infection for hospital and nursing home . First discovered in the late 2000s, Candida auris has very quickly become a major health challenge due to its ease of spread and ability to resist common antifungal drugs.

How did this fungus become so strong, and what can researchers and physicians do to combat it?

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I am a microbiologist researching new ways to kill fungi. Candida auris and other fungi use three common cellular tricks to overcome treatments. Luckily, exciting new research hints at ways we can still fight this fungus.

Drug-resistant Candida auris infections are on the rise in the U.S. and around the world.

Targeting the sensitive parts of fungal cells

Fungal cells contain a structure called a cell wall that helps maintain their shape and protects them from the . Fungal cell walls are constructed in part from several different types of polysaccharides, which are long strings of sugar molecules linked together.

Two polysaccharides found in almost all fungal cell walls are chitin and beta-glucan. The fungal cell wall is an attractive target for drugs because human cells do not have a cell wall, so drugs that block chitin and beta-glucan production will have fewer side effects.

Some of the most common drugs used to treat fungal infections are called echinocandins. These drugs stop fungal cells from making beta-glucan, which significantly weakens their cell wall. This means the fungal cell can't maintain its shape well. While the fungus is struggling to grow or is breaking apart, your immune system has a much better of fighting off the infection.

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How fungi become drug resistant

Unfortunately, some strains of Candida auris are resistant to echinocandin treatment. But how does the fungus actually do it? For decades, scientists have been studying how fungi overcome drugs designed to weaken or kill them. In the case of echinocandins, Candida auris commonly uses three tricks to beat these treatments: hide, build and change.

The first trick is to hide in a complex mixture of sugars, proteins, DNA and cells called a biofilm. Made with irregular 3D structures, biofilms have lots of places for cells to hide. Drugs aren't good at penetrating biofilms, so they can't access and kill cells deep inside. Biofilms are especially problematic when they grow on medical equipment like ventilators or catheters. Once of a biofilm, cells that have gained the ability to resist the drugs a patient was taking become more dangerous.

Microscopy image of two types of Candida attaching to each other
This image shows Candida albicans (red) producing branching filaments that allow it to attach to Candida glabrata (green), forming biofilms. Both of these species can cause infections in people.
Edgerton Lab, State University of New York at Buffalo/Flickr, CC BY-NC

The second trick fungi use to evade treatment is to build cell walls differently. Fungal cells treated with echinocandins can't make beta-glucan. So instead, they start to make more chitin, another important polysaccharide in the fungal cell wall. Echinocandins are unable to stop chitin production, so the fungus is still able to build a strong cell wall and avoid being killed. While there are some drugs that can stop chitin production, none are currently approved for use in people.

The third trick fungi rely on is to change the shape of the beta-glucan production enzyme so echinocandins cannot block it. These mutations allow beta-glucan production to continue even in the presence of the drug. It is not surprising that Candida uses this trick to resist antifungal drugs since it is very effective at keeping the cells alive.

New tactics to fight fungi

What can be done to treat echinocandin-resistant fungal infections? Thankfully, scientists and physicians are researching new ways to kill Candida auris and similar fungi.

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The first approach is to find new drugs. For example, there are two drugs in , rezafungin and ibrexafungerp, that appear to be able to stop beta-glucan production even in fungi resistant to echinocandins.

Microscopy image of budding yeast cells
This microscopy image shows budding yeast cells.
toeytoey2530/iStock via Getty Images Plus

A complementary approach my research group is exploring is whether a class of enzymes called glycoside hydrolases might also be able to combat drug-resistant fungi. Some of these enzymes actively destroy the fungal cell wall, breaking apart both beta-glucan and chitin at the same time, which could potentially prevent fungi from surviving on medical equipment or on hospital surfaces.

My lab's work on discovering enzymes that strongly degrade fungal cell walls is part of a new strategy to combat antifungal resistance that uses a combination of approaches to kill fungi. But the end goal of this research is the same: a physician tell you, “You've got a fungal infection, but we have a good treatment for it now.”The Conversation

Jeffrey Gardner, Associate Professor of Biological Sciences, University of Maryland, Baltimore County

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

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‘Dancing’ raisins − a simple kitchen experiment reveals how objects can extract energy from their environment and come to life

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theconversation.com – Saverio Eric Spagnolie, Professor of Mathematics, University of Wisconsin-Madison – 2024-05-13 07:29:32

Surface bubble growth can lift objects upward against gravity.

Saverio Spagnolie

Saverio Eric Spagnolie, University of Wisconsin-Madison

Scientific discovery doesn't always require a high-tech laboratory or a hefty budget. Many people have a first-rate lab right in their own homes – their kitchen.

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The kitchen offers plenty of opportunities to view and explore what physicists call soft matter and complex fluids. Everyday phenomena, such as Cheerios clustering in milk or rings left when drops of coffee evaporate, have led to discoveries at the intersection of physics and chemistry and other tasteful collaborations between food scientists and physicists.

Two , Sam Christianson and Carsen Grote, and I published a new study in Nature Communications in May 2024 that dives into another kitchen observation. We studied how objects can levitate in carbonated fluids, a phenomenon that's whimsically referred to as dancing raisins.

The study explored how objects like raisins can rhythmically move up and down in carbonated fluids for several minutes, even up to an hour.

An accompanying Twitter thread about our research went viral, amassing over half a million views in just two days. Why did this particular experiment catch the imaginations of so many?

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Bubbling physics

Sparkling and other carbonated beverages fizz with bubbles because they contain more gas than the fluid can support – they're “supersaturated” with gas. When you open a bottle of champagne or a soft drink, the fluid pressure drops and CO₂ molecules begin to make their escape to the surrounding .

Bubbles do not usually form spontaneously in a fluid. A fluid is composed of molecules that like to stick together, so molecules at the fluid boundary are a bit unhappy. This results in surface tension, a force which seeks to reduce the surface area. Since bubbles add surface area, surface tension and fluid pressure normally squeeze any forming bubbles right back out of existence.

But rough patches on a container's surface, like the etchings in some champagne glasses, can protect new bubbles from the crushing effects of surface tension, offering them a to form and grow.

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Bubbles also form inside the microscopic, tubelike cloth fibers left behind after wiping a glass with a towel. The bubbles grow steadily on these tubes and, once they're big enough, detach and float upward, carrying gas out of the container.

But as many champagne enthusiasts who put fruits in their glasses know, surface etchings and little cloth fibers aren't the only places where bubbles can form. Adding a small object like a raisin or a peanut to a sparkling drink also enables bubble growth. These immersed objects act as alluring new surfaces for opportunistic molecules like CO₂ to accumulate and form bubbles.

And once enough bubbles have grown on the object, a levitation act may be performed. Together, the bubbles can lift the object up to the surface of the liquid. Once at the surface, the bubbles pop, dropping the object back down. The then begins again, in a periodic vertical dancing motion.

Dancing raisins

Raisins are particularly good dancers. It takes only a few seconds for enough bubbles to form on a raisin's wrinkly surface before it starts to rise upward – bubbles have a harder time forming on smoother surfaces. When dropped into just-opened sparkling water, a raisin can dance a vigorous tango for 20 minutes, and then a slower waltz for another hour or so.

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Anyone with a few kitchen staples can do their own dancing raisins experiment.

We found that rotation, or spinning, was critically important for coaxing large objects to dance. Bubbles that cling to the bottom of an object can keep it aloft even after the top bubbles pop. But if the object starts to spin even a little bit, the bubbles underneath make the body spin even faster, which results in even more bubbles popping at the surface. And the sooner those bubbles are removed, the sooner the object can get back to its vertical dancing.

Small objects like raisins do not rotate as much as larger objects, but instead they do the twist, rapidly wobbling back and forth.

Modeling the bubbly flamenco

In the paper, we developed a mathematical model to predict how many trips to the surface we would expect an object like a raisin to make. In one experiment, we placed a 3D-printed sphere that acted as a model raisin in a glass of just-opened sparkling water. The sphere traveled from the bottom of the container to the top over 750 times in one hour.

The model incorporated the rate of bubble growth as well as the object's shape, size and surface roughness. It also took into account how quickly the fluid loses carbonation based on the container's geometry, and especially the flow created by all that bubbly activity.

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Small objects covered in bubbles in carbonated water move upwards towards the surface and back down.

Bubble-coated raisins ‘dance' to the surface and plummet once their lifting agents have popped.

Saverio Spagnolie

The mathematical model helped us determine which forces influence the object's dancing the most. For example, the fluid drag on the object turned out to be relatively unimportant, but the ratio of the object's surface area to its volume was critical.

Looking to the future, the model also provides a way to determine some hard to measure quantities using more easily measured ones. For example, just by observing an object's dancing frequency, we can learn a lot about its surface at the microscopic level without having to see those details directly.

Different dances in different theaters

These results aren't just interesting for carbonated beverage lovers, though. Supersaturated fluids exist in nature, too – magma is one example.

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As magma in a volcano rises closer to the Earth's surface, it rapidly depressurizes, and dissolved gases from inside the volcano make a dash for the exit, just like the CO₂ in carbonated water. These escaping gases can form into large, high-pressure bubbles and emerge with such force that a volcanic eruption ensues.

The particulate matter in magma may not dance in the same way raisins do in soda water, but tiny objects in the magma may affect how these explosive events play out.

The past decades have also seen an eruption of a different kind – thousands of scientific studies devoted to active matter in fluids. These studies look at things such as swimming microorganisms and the insides of our fluid-filled cells.

Most of these active do not exist in water but instead in more complicated biological fluids that contain the energy necessary to produce activity. Microorganisms absorb nutrients from the fluid around them to continue swimming. Molecular motors carry cargo along a superhighway in our cells by pulling nearby energy in the form of ATP from the .

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Studying these systems can help scientists learn more about how the cells and bacteria in the human body function, and how on this planet has evolved to its current .

Meanwhile, a fluid itself can behave strangely because of a diverse molecular composition and bodies moving around inside it. Many new studies have addressed the behavior of microorganisms in such fluids as mucus, for instance, which behaves like both a viscous fluid and an elastic gel. Scientists still have much to learn about these highly complex systems.

While raisins in soda water seem fairly simple when with microorganisms swimming through biological fluids, they offer an accessible way to study generic features in those more challenging settings. In both cases, bodies extract energy from their complex fluid environment while also affecting it, and fascinating behaviors ensue.

New insights about the physical world, from geophysics to biology, will continue to emerge from tabletop-scale experiments – and perhaps from right in the kitchen.The Conversation

Saverio Eric Spagnolie, Professor of Mathematics, University of Wisconsin-Madison

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Why do people hate people?

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theconversation.com – Kristine Hoover, Professor of Organizational Leadership, Gonzaga – 2024-05-13 07:16:27

Biases against certain groups of people can escalate into acts of violence if left unchecked.

Paul Taylor/Stone via Getty Images

Kristine Hoover, Gonzaga University and Yolanda Gallardo, Gonzaga University

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

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Why do people hate people? – Daisy, age 9, Lake Oswego, Oregon


Have you ever said “I hate you” to someone? What about using the “h-word” in casual conversation, like “I hate broccoli”? What are you really feeling when you say that you hate something or someone?

The Merriam-Webster dictionary describes the word “hate” as an “intense hostility and aversion usually deriving from fear, anger, or sense of injury.” All over the world, researchers like us are studying hate from disciplines like education, history, , leadership, psychology, sociology and many others.

If you had a scary experience with thunderstorms, you might say that you hate thunderstorms. Maybe you have gotten very angry at something that happened at a particular place, so now you say you hate going there. Maybe someone said something hurtful to you, so you say you hate that person.

Understanding hate as an emotional response can help you recognize your feelings about something or someone and be curious about where those feelings are coming from. This awareness will give you time to gather more information and imagine the other person's perspective.

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So what is hate and why do people hate? There are many answers to these questions.

What hate isn't

Hate, according to the U.S. Department of Justice, “does not mean rage, anger or general dislike.”

Sometimes people think they have to feel or believe a certain way about another person or group of people because of what they hear or see around them. For example, people might say they hate another person or group of people when what they really mean is that they don't agree with them, don't understand them or don't like how they behave or the things they believe in.

View between the arm of a person with their hands on their hips, focusing on a child sitting at table with a glare

Do you hate this person, or are you angry, or afraid?

Lourdes Balduque/Moment via Getty Images

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It is easy to blame others for things you don't believe or experiences you don't like. Think about times you might have heard someone at school say they hate a classmate or a teacher. Could they have been angry, hurt or confused about something but used the word hate to explain or name how they were feeling?

When you don't understand someone else, it can make you nervous and even afraid. Instead of being curious about each other's unique experiences, people may judge others for being different – they may have a different skin color, practice a different religion, come from a different country, be older or younger, or use a wheelchair.

When people judge people as being less important or less human than themselves, that is a form of hatred.

What hate is

The U.S. Department of Justice defines hate as “bias against people or groups with specific characteristics that are defined by the law.” These characteristics can include a person's race, religion, gender, sexual orientation, disability and national origin.

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One way to think about hate is as a pyramid. At the bottom of the pyramid, hate is a feeling that grows from biased attitudes about others, like stereotypes that certain groups of people are animals, lazy or stupid.

Sometimes these biased attitudes and feelings a foundation for people to act out their biases, such as through bullying, exclusion or insults. For example, many Asian people in the U.S. experienced an increase in hate incidents during the pandemic. If communities accept biases as OK, some people may move up the pyramid and think it is also OK to discriminate, or believe that specific groups of people are not welcome in certain neighborhoods or because of who they are.

Near the top of the pyramid, some people commit violence or hate crimes because they believe their own way of being is better than others'. They may threaten or physically harm others, or destroy property. At the very top of the pyramid is genocide, the intent to destroy a particular group – like what Jewish people experienced during World War II or what Rohingya people are experiencing in Myanmar, near China.

Hate at the middle and higher levels of the pyramid happens because no one took action to discourage the biased feelings, attitudes and actions at the lower levels of the pyramid.

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Taking action against hate

Not only can individual people hate, there are also hate groups like the Ku Klux Klan that attack people who are not white, straight or Christian. Sometimes hate has been written into law like the Indian Removal Act or Jim Crow laws that persecuted Native and Black Americans. If we stay silent when we encounter hate, that hatred can grow and do greater levels of harm.

There are many ways you can help stop hate in your everyday life.

Pay attention to what is being said around you. If the people you spend a lot of time with are saying hateful things about other groups, consider speaking up or changing who you hang out with and where. Be an upstander – sit with someone who is being targeted and report when you see or hear hate incidents.

Close-up of group of protestors yelling with their fists in the air

Protests are one way people speak up on behalf of a specific group.

FG Trade/E+ via Getty Images

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Start noticing when you are letting hateful words or behaviors into your thoughts and actions. Get to know what hate looks and sounds like in yourself and in others, what you see online.

Be open to meeting others who have different experiences than you and give them a chance to let you know who they are. Be brave and face your fears. Be curious and kind.

You are not alone in standing up to hate. Many human rights groups and government initiatives are doing the work of eradicating hate, too. We all have a “response-ability,” or the ability to respond. As civil rights leader the Rev. Martin Luther King Jr. said, “Darkness cannot drive out darkness, only light can do that. Hate cannot drive out hate, only love can do that.”

You just might find that it is easier to love other people than to hate them. Others will see how you behave and will follow your lead.

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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 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

Kristine Hoover, Professor of Organizational Leadership, Gonzaga University and Yolanda Gallardo, Dean of Education, Gonzaga University

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

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Algorithms help people see and correct their biases, study shows

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theconversation.com – Carey K. Morewedge, Professor of Marketing and Everett W. Lord Distinguished Faculty Scholar, Boston – 2024-05-10 07:27:14

Algorithms could serve as mirrors for you to check your biases.

FG Trade/E+ via Getty Images

Carey K. Morewedge, Boston University

Algorithms are a staple of modern life. People rely on algorithmic recommendations to wade through deep catalogs and find the best movies, routes, information, products, people and investments. Because people train algorithms on their decisions – for example, algorithms that make recommendations on e-commerce and social sites – algorithms learn and codify human biases.

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Algorithmic recommendations exhibit bias toward popular choices and information that evokes outrage, such as partisan news. At a societal level, algorithmic biases perpetuate and amplify structural racial bias in the judicial system, gender bias in the people companies hire, and wealth inequality in urban development.

Algorithmic bias can also be used to reduce human bias. Algorithms can reveal hidden structural biases in organizations. In a paper published in the Proceedings of the National Academy of Science, my colleagues and I found that algorithmic bias can people better recognize and correct biases in themselves.

The bias in the mirror

In nine experiments, Begum Celikitutan, Romain Cadario and I had research participants rate Uber drivers or Airbnb listings on their driving skill, trustworthiness or the likelihood that they would rent the listing. We gave participants relevant details, like the number of trips they'd driven, a description of the property, or a star rating. We also included an irrelevant biasing piece of information: a photograph revealed the age, gender and attractiveness of drivers, or a name that implied that listing were white or Black.

After participants made their ratings, we showed them one of two ratings summaries: one showing their own ratings, or one showing the ratings of an algorithm that was trained on their ratings. We told participants about the biasing feature that might have influenced these ratings; for example, that Airbnb guests are less likely to rent from hosts with distinctly African American names. We then asked them to judge how much influence the bias had on the ratings in the summaries.

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The author how algorithms can be useful as a mirror of people's biases.

Whether participants assessed the biasing influence of race, age, gender or attractiveness, they saw more bias in ratings made by algorithms than themselves. This algorithmic mirror effect held whether participants judged the ratings of real algorithms or we showed participants their own ratings and deceptively told them that an algorithm made those ratings.

Participants saw more bias in the decisions of algorithms than in their own decisions, even when we gave participants a cash bonus if their bias judgments the judgments made by a different participant who saw the same decisions. The algorithmic mirror effect held even if participants were in the marginalized category – for example, by identifying as a woman or as Black.

Research participants were as able to see biases in algorithms trained on their own decisions as they were able to see biases in the decisions of other people. Also, participants were more likely to see the influence of racial bias in the decisions of algorithms than in their own decisions, but they were equally likely to see the influence of defensible features, like star ratings, on the decisions of algorithms and on their own decisions.

Bias blind spot

People see more of their biases in algorithms because the algorithms people's bias blind spots. It is easier to see biases in others' decisions than in your own because you use different evidence to evaluate them.

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When examining your decisions for bias, you search for evidence of conscious bias – whether you thought about race, gender, age, status or other unwarranted features when deciding. You overlook and excuse bias in your decisions because you lack access to the associative machinery that drives your intuitive judgments, where bias often plays out. You might think, “I didn't think of their race or gender when I hired them. I hired them on merit alone.”

The bias blind spot explained.

When examining others' decisions for bias, you lack access to the processes they used to make the decisions. So you examine their decisions for bias, where bias is evident and harder to excuse. You might see, for example, that they only hired white .

Algorithms remove the bias blind spot because you see algorithms more like you see other people than yourself. The -making processes of algorithms are a black box, similar to how other people's thoughts are inaccessible to you.

Participants in our study who were most likely to demonstrate the bias blind spot were most likely to see more bias in the decisions of algorithms than in their own decisions.

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People also externalize bias in algorithms. Seeing bias in algorithms is less threatening than seeing bias in yourself, even when algorithms are trained on your choices. People put the blame on algorithms. Algorithms are trained on human decisions, yet people call the reflected bias “algorithmic bias.”

Corrective lens

Our experiments show that people are also more likely to correct their biases when they are reflected in algorithms. In a final experiment, we gave participants a to correct the ratings they evaluated. We showed each participant their own ratings, which we attributed either to the participant or to an algorithm trained on their decisions.

Participants were more likely to correct the ratings when they were attributed to an algorithm because they believed the ratings were more biased. As a result, the final corrected ratings were less biased when they were attributed to an algorithm.

Algorithmic biases that have pernicious effects have been well documented. Our findings show that algorithmic bias can be leveraged for good. The first step to correct bias is to recognize its influence and direction. As mirrors revealing our biases, algorithms may improve our decision-making.The Conversation

Carey K. Morewedge, Professor of Marketing and Everett W. Lord Distinguished Faculty Scholar, Boston University

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