New approach uses 'cloaked' proteins to deliver cancer-killing therapeutics into cells

Image
Schematic of the bioreversible anionic cloaking strategy. Chemical modification of surface-exposed lysines with sulfonated cloaking reagents enables complexation and subsequent delivery of protein cargos with cationic lipids. Following endocytic escape, the reagents are cleaved off via the presence of a self-immolative, redox-sensitive disulfide bond to tracelessly deliver the cargo protein in the cytoplasm of a cell. Credit: ACS Central Science (2024). DOI: 10.1021/acscentsci.4c00071 An interdisciplinary collaboration has designed a way to «cloak» proteins so that they can be captured by lipid nanoparticles, which are akin to tiny bubbles of fat. These bubbles are small enough to sneak their hidden cargo into living cells, where the proteins uncloak and exert their therapeutic effect. The generalizable technique could lead to repurposing thousands of commercial protein products, including antibodies, for biological research an...

This Strange Fungal Condition Makes You Drunk without Drinking

This Strange Fungal Condition Makes You Drunk without Drinking

Greater awareness is needed around auto-brewery syndrome, which can cause dangerous accidents and trigger social ostracism if it is not correctly diagnosed

Close-up photo of a sign with an alcohol prohibited symbol hanging in an outdoor park

The woman had visited various emergency departments in Toronto six times over the past two years, always complaining of the same symptoms. She’d be at home, getting ready for work or preparing meals for her family when, seemingly out of nowhere, she’d suddenly become excessively tired and groggy. Her words would start to slur, and she’d lose motor coordination, sometimes causing her to fall. Her breath would begin to smell of alcohol, and her blood alcohol level would spike. In other words, she was drunk.

But the woman had consumed no alcoholic beverages. In fact, she’d given up drinking years before because of religious beliefs. She repeatedly related to doctors that she was a teetotaler, as did her husband. Yet each time she wound up at the hospital, she was diagnosed with alcohol intoxication. On one visit, an emergency room doctor even certified her under Ontario’s Mental Health Act to be involuntarily kept at the hospital until a psychiatric assessment could take place.

The woman’s seventh visit to the emergency department finally broke this pattern. Brian Goldman, an emergency physician at Mount Sinai Hospital in Toronto, actually listened to her story. Then, he did something strange: he prescribed an antifungal medication and referred her to a gastroenterologist. Goldman suspected that the woman had auto-brewery syndrome, a rare condition in which a person’s gut ferments alcohol from carbohydrate-heavy meals and causes them to become intoxicated without ever having consumed any alcohol.


On supporting science journalism

If you’re enjoying this article, consider supporting our award-winning journalism by subscribing. By purchasing a subscription you are helping to ensure the future of impactful stories about the discoveries and ideas shaping our world today.


As the woman’s emergency department odyssey demonstrated, knowledge about this syndrome is lacking, including in the medical community. In an effort to raise awareness, Goldman and several others decided to attempt to give the syndrome a broader profile by using the woman’s story as a case study, which they published last week in the Canadian Medical Association Journal.

“It was very distressing for our patient and her husband to continue repeating their same story for two years,” says the study’s lead author Rahel Zewude, a physician and infectious disease and medical microbiology fellow at the University of Toronto. “We thought sharing her story would be a great way to disseminate knowledge about this syndrome and hopefully shorten the diagnosis time in the future.”

Auto-brewery syndrome was first reported in 1948 by physicians in Uganda who had noticed a strong smell of alcohol while performing abdominal surgery on a five-year-old boy. No indications pointed to the boy having consumed alcohol earlier in the day. But he had eaten a sweet potato, and the doctors wondered if his digestive tract had somehow fermented it. The syndrome was officially described in 1952 in Japan. Dozens of cases have been reported in Japan since then, and 20 additional cases were described in the English-language medical literature between 1974 and 2020. Cases have occurred in countries around the world and in people ranging in age from children to older adults.

From those rare cases, doctors and scientists have hypothesized that auto-brewery syndrome occurs when alcohol-fermenting fungi—usually brewer’s yeast (Saccharomyces cerevisiae) or Candida species, both of which naturally occur in the human body—become overpopulated in a person’s gut. Certain bacteria can also ferment alcohol and, in extremely rare cases, auto-brewery syndrome has been linked to an overpopulation of the bacteria Klebsiella pneumoniae.

The currently understood mechanism for how this happens involves a number of factors that may contribute to an increased likelihood of the syndrome developing. These include having taken frequent or prolonged courses of antibiotics; having diabetes, inflammatory bowel disease or liver disease; and having a possible genetic predisposition through mutations that affect specific enzymes that help to metabolize and eliminate alcohol. “These factors need to collide together to create the perfect storm,” Zewude says.

That said, she adds, some people who come down with the syndrome don’t seem to have any risk factors at all.

Intoxication from auto-brewery syndrome is triggered when someone eats a carb-heavy meal, and episodes typically last the same amount of time that someone who was intoxicated by drinking alcohol would experience. People may also suffer intense hangoverlike symptoms in the following days. After returning from the hospital, the woman in the current case study would spend up to a week recovering in bed.

The syndrome has not been reported to cause death from lethal blood alcohol levels. But there have been people who have incurred major medical consequences, including one person who fell down while intoxicated and suffered a brain bleed and another who broke her ribs and nose. There have also been several cases of people who suddenly became intoxicated while driving, Zewude says. “You can imagine how devastating those consequences might be.”

People’s performance at work may also be impacted, and relationships with family members may become strained. Mental health can suffer as a result. “Everyone smells the alcohol on your breath, and you’re behaving like you’re drunk, but you’re denying that you’re drinking, and no one is believing you, including your doctors,” Zewude says. “That’s very distressing.”

“This study was important to publish,” says Michael Silverman, an assistant professor of medicine and infectious diseases at Western University in Ontario, who was not involved in the work. “Missing the diagnosis can be associated with severe outcomes.”

Fortunately, when diagnosed properly, auto-brewery syndrome is treatable with a course of antifungals. Typically, people with the condition also need to adhere to a low-carb diet, potentially for the long term. “Every patient is a bit different, so treatment approaches need to be tailored to them,” Zewude says. “Our patient hasn’t had a relapse for months now, and we hope that will continue to be the trajectory for her.”

Comments

Popular posts from this blog

New approach uses 'cloaked' proteins to deliver cancer-killing therapeutics into cells

New catalyst brings commercial high-efficiency zinc-air batteries closer to reality

Biologists find nanoplastics in developing chicken heart