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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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Under the influence and under arrest − what happens if you’re drunk in the interrogation room?

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theconversation.com – Jacqueline R. Evans, Associate Professor of Psychology, Florida International – 2024-04-26 07:28:33

In the U.S., if you waive your Miranda rights, you'll be interrogated – whether you're drunk or sober.

Photoboyko/iStock via Getty Images Plus

Jacqueline R. Evans, Florida International University

Imagine it's Friday night. You're enjoying happy hour with friends after a long . You're relaxed, indulged in several of your preferred adult beverages. Now imagine that as you the bar, a officer approaches. You're under arrest.

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Flash forward to the police station. The officer takes you to a cramped room and reads you your Miranda rights: You have the right to remain silent, to an attorney, and all the rest. Let's say you waive those rightsmost people do – and the officer questions you for several hours.

While under the influence, would you understand your Miranda rights and appreciate the consequences of choosing to invoke or waive them? Would the statements you made during questioning be more or less reliable than how you'd respond sober? Would a jury take what the drunken you said seriously? These are the questions that legal psychologists like me and my colleagues seek to address in our research.

Suspects get similar treatment, drunk or not

When we've surveyed police, they revealed it's common to question intoxicated suspects and that they tend to use the same interrogation techniques with drunken suspects that they normally use. Surveys of community members about their experience with interrogation confirm that questioning drunken suspects is common. In fact, sometimes police even interrogate drunken juveniles.

Of course, police in the U.S. cannot legally question anyone in custody unless that person has waived their Miranda rights and chosen to talk to the investigator. It's a common misperception that drunken people cannot legally waive their Miranda rights and that statements given while intoxicated cannot be used against them in court. But the reality is that from a legal perspective the police can Mirandize you while you're under the influence, interrogate you, and use your statements against you.

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arrow upwards with text describing expected impairments at increasing BAC levels

Level of impairment rises along with how much you've had to drink.

NIH National Institute on Alcohol Abuse and Alcoholism, CC BY

Consider the case of Travis Jewell. When he was for fleeing a police officer in his truck, his blood alcohol level was .29, more than three times the legal limit of .08 in the U.S. The interrogator reported Jewell was slurring words and struggling to stand. Nonetheless, the court accepted his Miranda waiver, making Jewell's statements admissible during trial.

While Miranda waivers from intoxicated people may be legally valid, research from my lab suggests that when compared with sober individuals, someone under the influence of or alcohol – even at low levels of intoxication – may be less able to comprehend their rights.

Testing how drunken ‘suspects' behave

Critically, researchers know almost nothing about how intoxicated people behave during interrogation.

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To address this need, my colleagues and I brought university student volunteers into the lab, where we have safeguards in place to minimize risks. We had some of our participants drink enough vodka to reach a breath alcohol level of .08%, a level consistent with the legal driving limit in the U.S.

Then we set the participants up to be guilty or innocent of cheating, and interrogated each of them about potential academic misconduct. We were interested in whether, impaired or sober, they said anything incriminating or suspicious during questioning.

About two-thirds of sober participants said something suggestive of guilt, while even more intoxicated participants did. The difference in suspicious statements between the groups was not statistically significant, but our findings do indicate that intoxicated people – just like the rest of the public – are at a high risk of self-incrimination. And remember, in our study, half of the participants were innocent of the infraction they were being questioned about.

man in striped clothes sits across table from woman in suit jacket

Standard legal advice is to keep your mouth shut until you are able to meet with a lawyer.

AP Photo/Steve Helber

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Suspicious remarks can have immediate consequences during interrogation. When a says something suggestive of guilt, it tends to increase an interrogator's belief that they're guilty. When interrogators have a stronger belief in guilt, they then tend to be more accusatory, an approach associated with false confessions.

Intoxicated suspects – guilty or innocent – are very likely to make a guilt-suggestive statement, which in turn is likely to invite more coercive interrogation approaches. This could potentially explain our recent real-world findings in Sweden that police interrogators used more confrontational techniques with intoxicated suspects than with sober suspects.

On a positive note, our work has also shown that potential jurors seem to recognize that intoxication may to less reliable statements during interrogation. They tend to give less weight to a confession from an intoxicated suspect than from a sober suspect. While that may sound reassuring, should you find yourself in that cramped interrogation room, sober or intoxicated, exercise your rights and ask for an attorney.The Conversation

Jacqueline R. Evans, Associate Professor of Psychology, Florida International University

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

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Cybersecurity researchers spotlight a new ransomware threat – be careful where you upload files

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theconversation.com – Selcuk Uluagac, Professor of Computing and Information Science, Florida International University – 2024-04-26 07:28:18

Avoiding iffy downloads is no longer enough to ensure this doesn't happen.

Olemedia/iStock via Getty Images

Selcuk Uluagac, Florida International University

You probably know better than to click on links that download unknown files onto your computer. It turns out that uploading files can get you into trouble, too.

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Today's web browsers are much more powerful than earlier generations of browsers. They're able to manipulate data within both the browser and the computer's local file system. Users can send and email, listen to music or watch a within a browser with the click of a button.

Unfortunately, these capabilities also mean that hackers can find clever ways to abuse the browsers to trick you into letting ransomware lock up your files when you think that you're simply doing your usual tasks online.

I'm a computer scientist who studies cybersecurity. My colleagues and I have shown how hackers can gain access to your computer's files via the File System Access Application Programming Interface (API), which enables web applications in modern browsers to interact with the users' local file .

The threat applies to Google's Chrome and Microsoft's Edge browsers but not Apple's Safari or Mozilla's Firefox. Chrome accounts for 65% of browsers used, and Edge accounts for 5%. To the best of my knowledge, there have been no reports of hackers using this method so far.

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My colleagues, who include a Google security researcher, and I have communicated with the developers responsible for the File System Access API, and they have expressed support for our work and interest in our approaches to defending against this kind of attack. We also filed a security report to Microsoft but have not heard from them.

Double-edged sword

Today's browsers are almost operating systems unto themselves. They can run software programs and encrypt files. These capabilities, combined with the browser's access to the host computer's files – including ones in the cloud, shared folders and external drives – via the File System Access API creates a new for ransomware.

Imagine you want to edit photos on a benign-looking online editing tool. When you upload the photos for editing, any hackers who control the malicious editing tool can access the files on your computer via your browser. The hackers would gain access to the folder you are uploading from and all subfolders. Then the hackers could encrypt the files in your file system and demand a ransom payment to decrypt them.

Today's web browsers are more powerful – and in some ways more vulnerable – than their predecessors.

Ransomware is a growing problem. Attacks have hit individuals as well as , including Fortune 500 companies, , cloud service providers, cruise operators, threat-monitoring services, chip manufacturers, governments, medical centers and hospitals, insurance companies, schools, universities and even police departments. In 2023, organizations paid more than US$1.1 billion in ransomware payments to attackers, and 19 ransomware attacks targeted organizations every second.

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It is no wonder ransomware is the No. 1 arms race today between hackers and security specialists. Traditional ransomware runs on your computer after hackers have tricked you into downloading it.

New defenses for a new threat

A team of researchers I at the Cyber-Physical Systems Security Lab at Florida International University, including postdoctoral researcher Abbas Acar and Ph.D. candidate Harun Oz, in collaboration with Google Senior Research Scientist Güliz Seray Tuncay, have been investigating this new type of potential ransomware for the past two years. Specifically, we have been exploring how powerful modern web browsers have become and how they can be weaponized by hackers to create novel forms of ransomware.

In our paper, RøB: Ransomware over Modern Web Browsers, which was presented at the USENIX Security Symposium in August 2023, we showed how this emerging ransomware strain is easy to design and how damaging it can be. In particular, we designed and implemented the first browser-based ransomware called RøB and analyzed its use with browsers running on three different major operating systems – Windows, Linux and MacOS – five cloud providers and five antivirus products.

Our evaluations showed that RøB is capable of encrypting numerous types of files. Because RøB runs within the browser, there are no malicious payloads for a traditional antivirus program to catch. This means existing ransomware detection systems face several issues against this powerful browser-based ransomware.

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We proposed three different defense approaches to mitigate this new ransomware type. These approaches operate at different levels – browser, file system and user – and complement one another.

The first approach temporarily halts a web application – a program that runs in the browser – in order to detect encrypted user files. The second approach monitors the activity of the web application on the user's computer to identify ransomware-like patterns. The third approach introduces a new permission dialog box to inform users about the risks and implications associated with allowing web applications to access their computer's file system.

When it to protecting your computer, be careful about where you upload as well as download files. Your uploads could be giving hackers an “in” to your computer.The Conversation

Selcuk Uluagac, Professor of Computing and Information Science, Florida International University

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

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How bird flu virus fragments get into milk sold in stores, and what the spread of H5N1 in cows means for the dairy industry and milk drinkers

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theconversation.com – Noelia Silva del Rio, Associate Specialist in Cooperative Extension, Production Medicine and Food Safety, of California, Davis – 2024-04-25 14:04:50

Cows typically get over avian flu in a of weeks, but it's an economic blow for farms.

AP Photo/Charlie Litchfield

Noelia Silva del Rio, University of California, Davis; Richard V. Pereira, University of California, Davis; Robert B. Moeller, University of California, Davis; Terry W. Lehenbauer, University of California, Davis, and Todd Cornish, University of California, Davis

The discovery of viral fragments of avian flu virus in milk sold in U.S. stores suggests that the H5N1 virus may be more widespread in U.S. dairy cattle than previously realized.

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The Food and Drug Administration was quick to stress on April 24, 2024, that it believes the commercial milk supply is safe. However, highly pathogenic avian influenza virus can make cows sick, and the flu virus's presence in herds in several states and now new federal restrictions on the movement of dairy cows between states are putting economic pressure on farmers.

Five experts in infectious diseases in cattle from the University of California, Davis – Noelia Silva del Rio, Terry Lehenbauer, Richard Pereira, Robert Moeller and Todd Cornish – explain what the test results mean, how bird flu can spread to cattle and the impact on the industry.

What are viral fragments of avian flu, and can they pose risks to people?

It's crucial to understand that the presence of viral fragments of H5N1 doesn't indicate the presence of intact virus particles that could cause disease.

The commercial milk supply maintains safety through two critical measures:

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  • First, milk sourced from sick animals is promptly diverted or disposed of, ensuring it does not enter the food chain.

  • Second, all milk at grocery stores is heat treated to reduce pathogen load to safe levels, mainly by pasteurization. Pasteurization has been shown to effectively inactivate H5N1 in eggs, and that occurs at a lower temperature than is used for milk.

The viral fragments were detected using quantitative polymerase chain reaction testing, which is known for its exceptional sensitivity in detecting even trace amounts of viral genetic material. These fragments are only evidence that the virus was present in the milk. They aren't evidence that the virus is biologically active.

To evaluate whether the presence of the viral fragments corresponds to a virus with the capacity to replicate and cause disease, a different testing approach is necessary. Tests such as embryonated egg viability studies allow scientists to assess the virus's ability to replicate by injecting a sample into an embryonated chicken egg. That type of testing is underway.

On April 24, 2024, the FDA said it had found no reason to change its assessment that the U.S. milk supply is safe. The agency does strongly advise against consuming raw milk and products derived from it because of its inherent risks of contamination with harmful pathogens, avian flu viruses.

How does an avian flu virus get into cow's milk?

Currently, cows confirmed to have H5N1 have different symptoms than the typical flu-like symptoms observed in birds.

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Abnormal milk and mastitis, an inflammatory response to infection, are common. While there is speculation that other bodily secretions, such as saliva, respiratory fluids, urine or feces, may also harbor the virus, that has yet to be confirmed.

The legs of a cow showing a milking device attached to the udder and tubes for the milk to flow.

Milking equipment can help viruses spread.

Loic Venance/AFP via Getty Images

How waterfowl or other birds transmitted H5N1 to cattle is still under investigation. In 2015, an outbreak of highly pathogenic avian influenza in commercial poultry farms reached its peak in April and May, the same time birds migrated north. Birds can shed the virus through their oral, nasal, urine and fecal secretions. So the virus could potentially be transmitted through direct contact, ingesting contaminated feed or water, or inhaling the virus.

Infected dairy cows can shed the virus in milk, and they likely can transmit it to other cows, but that still needs to be proven.

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Contagious pathogens that cause mastitis can be transmitted through milking equipment or contaminated milker's gloves. Ongoing research will help determine whether this is also a potential transmission route for H5N1, and if so, what makes the virus thrive on mammary tissue.

If H5N1 is found to be widespread in milk, what risks can that pose for the dairy industry?

For the dairy industry, infection of cattle with H5N1 avian influenza virus creates challenges at two levels.

The overriding concern is always for the safety and healthfulness of milk and dairy products.

Existing and federal regulations and industry practices require sick cows or cows with abnormal milk to be segregated so that their milk does not enter the food supply. Proper pasteurization should kill the virus so that it cannot cause infection.

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The American Association of Bovine Practitioners has also developed biosecurity guidelines for H5N1, focusing on key practices. These include minimizing wild birds' contact with cattle and their , managing the movement of cattle between farms, isolating affected animals, avoiding feeding unpasteurized (raw) colostrum or milk to calves and other mammals, and ensuring the use of protective personal equipment for animal caretakers.

The other major concern is for the of the dairy herd and the people who take care of the dairy cattle. A farm worker who handled dairy cows contracted H5N1 in Texas in March 2024, but such cases are rare.

No vaccines or specific therapies are available for avian influenza infections in dairy cattle. But good sanitation and biosecurity practices for both people and cows will help to reduce risk of exposure and spread of the avian influenza virus among dairy cattle.

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For cows that get the virus, providing supportive care, including fluids and fever reducers as needed, can help them get through the illness, which can also cause loss of appetite and affect their milk production.

Dairy farms facing an outbreak will have economic losses from caring for sick animals and the temporary reduction in milk sales. Approximately 5% to 20% of the animals in the affected herds have become ill, according to early estimates. Affected animals typically recover within 10 to 20 days.

At least 21 states have restricted importing dairy cattle to prevent the virus's spread, and the federal announced it will require that lactating dairy cattle be tested before they can be moved between states starting April 29, 2024. While the overall impact on U.S. milk production is projected to be minor on an annual basis, it could lead to short-lived supply disruptions.

How worried should people be about avian flu?

The federal government's monitoring and food safety measures, along with pasteurization, important safeguards to protect the public from potential exposure to avian influenza virus through the food chain.

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Drinking raw milk, however, does represent a risk for exposure to multiple diseases, including H5N1. This is why the FDA and Centers for Disease Control and Prevention strongly recommend drinking only pasteurized milk and dairy products.The Conversation

Noelia Silva del Rio, Associate Specialist in Cooperative Extension, Production Medicine and Food Safety, University of California, Davis; Richard V. Pereira, Associate Professor of Veterinary Medicine and Associate Agronomist, University of California, Davis; Robert B. Moeller, Professor of Veterinary Medicine, University of California, Davis; Terry W. Lehenbauer, Professor of Veterinary Medicine, University of California, Davis, and Todd Cornish, Professor of Veterinary Medicine, University of California, Davis

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

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