Penicillin, effective against many bacterial infections, is often a first-line antibiotic. Yet it is also one of the most common causes of drug allergies. Around 10 percent of people say they’ve had an allergic reaction to penicillin, according to the U.S. Centers for Disease Control and Prevention.

Now researchers have found a genetic link to the hypersensitivity, which, while rarely fatal, can cause hives, wheezing, arrythmias and more.

People who report penicillin allergies can have a genetic variation on an immune system gene that helps the body distinguish between our own cells and harmful bacteria and viruses. That hot spot is on the major histocompatibility complex gene HLA-B, said Kristi Krebs, a pharmacogenomics researcher for the Estonian Genome Center at the University of Tartu. She presented the finding October 26 at the American Society of Human Genetics 2020 virtual meeting. The research was also published online October 1 in the American Journal of Human Genetics.

Several recent studies have connected distinct differences in HLA genes to bad reactions to specific drugs. For example, studies have linked an HLA-B variant to adverse reactions to an HIV/AIDS medication called abacavir, and they’ve linked a different HLA-B variant to allergic reactions to the gout medicine allopurinol. “So it’s understandable that this group of HLA variants can predispose us to higher risk of allergic drug reactions,” says Bernardo Sousa-Pinto, a researcher in drug allergies and evidence synthesis at the University of Porto in Portugal, who was not involved in the study.

For the penicillin study, the team hunted through more than 600,000 electronic health records that included genetic information for people who self-reported penicillin allergies. The researchers used several genetic search tools, which comb through DNA in search of genetic variations that may be linked to a health problem. Their search turned up a specific spot on chromosome 6, on a variant called HLA-B*55:01.

The group then checked its results against 1.12 million people of European ancestry in the research database of the genetic-testing company 23andMe and found the same link. A check of smaller databases including people with East Asian, Middle Eastern and African ancestries found no similar connection, although those sample sizes were too small to be sure, Krebs said

It’s too soon to tell if additional studies will “lead to better understanding of penicillin allergy and also better prediction,” she said.

Penicillin allergies often begin in childhood, but can wane over time, making the drugs safer to use some years later, Sousa-Pinto says. In this study, self-reported allergies were not confirmed with a test, so there’s a chance that some participants were misclassified. This is very common, Sousa-Pinto says. “It would be interesting to replicate this study in … participants with confirmed penicillin allergy.”

The distinction matters, because about 90 percent of patients who claim to be allergic to penicillin can actually safely take the drug (SN: 12/11/16). Yet, Sousa-Pinto says, those people may be given a more-expensive antibiotic that may not work as well. Less-effective antibiotics can make patients more prone to infections with bacteria that are resistant to the drugs. “This … is something that has a real impact on health care and on health services,” he says.

The fate of a potential new Alzheimer’s drug is still uncertain. Evidence that the drug works isn’t convincing enough for it to be approved, outside experts told the U.S. Food and Drug Administration during a Nov. 6 virtual meeting that at times became contentious.

The scientists and clinicians were convened at the request of the FDA to review the evidence for aducanumab, a drug that targets a protein called amyloid-beta that accumulates in the brains of people with Alzheimer’s. The drug is designed to stick to A-beta and stop it from forming larger, more dangerous clumps. That could slow the disease’s progression but not stop or reverse it.

When asked whether a key clinical study provided strong evidence that the drug effectively treated Alzheimer’s, eight of 11 experts voted no. One expert voted yes, and two were uncertain.

The FDA is not bound to follow the recommendations of the guidance committee, though it has historically done so. If ultimately approved, the drug would be a milestone, says neurologist and neuroscientist Arjun Masurkar of New York University Langone’s Alzheimer’s Disease Research Center. Aducanumab “would be the first therapy that actually targets the underlying disease itself and slows progression.”

Developed by the pharmaceutical company Biogen, which is based in Cambridge, Mass., the drug is controversial. That’s because two large clinical trials of aducanumab have yielded different outcomes, one positive and one negative (SN: 12/5/19). The trials were also paused at one point, based on analyses that suggested the drug didn’t work.

Those unusual circumstances created gaps in the evidence, leaving big questions in some scientists’ minds about whether the drug is effective. Aducanumab’s ability to treat Alzheimer’s “cannot be proven by clinical trials with divergent outcomes,” researchers wrote in a perspective article published November 1 in Alzheimer’s & Dementia. The drug should be tested again with a different clinical trial, those researchers say.

But other groups, including the Alzheimer’s Association, are rooting for the drug. In a letter sent to the FDA on October 23, the nonprofit health organization urged aducanumab’s approval, along with longer-term studies of the drug.

“While the trial data has led to some uncertainty among the scientific community, this must be weighed against the certainty of what this disease will do to millions of Americans absent a treatment,” Joanne Pike, chief strategy officer of the Alzheimer’s Association, wrote in the letter. She noted that by 2050, more than 13 million Americans 65 and older may have Alzheimer’s. More than 5 million Americans currently have the disease.

Even with an eventual approval, questions would remain for patients and their caregivers, says Zaldy Tan, a geriatric memory specialist at Cedars-Sinai Medical Center in Los Angeles. “Cost and logistics are going to be complex issues to tackle,” he says. One estimate puts aducanumab’s price tag at $40,000 annually, and treatment would require injections, for instance, which would require regular visits to a health care facility.

Bacteria go to extremes to handle hard times: They hunker down, building a fortress-like shell around their DNA and turning off all signs of life. And yet, when times improve, these dormant spores can rise from the seeming dead.

But “you gotta be careful when you decide to come back to life,” says Peter Setlow, a biochemist at UConn Health in Farmington. “Because if you get it wrong, you die.” How is a spore to tell?

For spores of the bacterium Bacillus subtilis, the solution is simple: It counts.

These “living rocks” sense it’s time to revive, or germinate, by essentially counting how often they encounter nutrients, researchers report in a new study in the Oct. 7 Science.
“They appear to have literally no measurable biological activity,” says Gürol Süel, a microbiologist at the University of California, San Diego. But Süel and his colleagues knew that spores’ cores contain positively charged potassium atoms, and because these atoms can move around without the cell using energy, the team suspected that potassium could be involved in shocking the cells awake.

So the team exposed B. subtilis spores to nutrients and used colorful dyes to track the movement of potassium out of the core. With each exposure, more potassium left the core, shifting its electrical charge to be more negative. Once the spores’ cores were negatively charged enough, germination was triggered, like a champagne bottle finally popping its cork. The number of exposures it took to trigger germination varied by spore, just like some corks require more or less twisting to pop. Spores whose potassium movement was hamstrung showed limited change in electric charge and were less likely to “pop” back to life no matter how many nutrients they were exposed to, the team’s experiments showed.

Changes in the electrical charge of a cell are important across the tree of life, from determining when brain cells zip off messages to each other, to the snapping of a Venus flytrap (SN: 10/14/20). Finding that spores also use electrical charges to set their wake-up calls excites Süel. “You want to find principles in biology,” he says, “processes that cross systems, that cross fields and boundaries.”

Spores are not only interesting for their unique and extreme biology, but also for practical applications. Some “can cause some rather nasty things” from food poisoning to anthrax, says Setlow, who was not involved in the study. Since spores are resistant to most antibiotics, understanding germination could lead to a way to bring them back to life in order to kill them for good.

Still, there are many unanswered questions about the “black box” of how spores start germination, like whether it’s possible for the spores to “reset” their potassium count. “We really are in the beginnings of trying to fill in that black box,” says Kaito Kikuchi, a biologist now at Reveal Biosciences in San Diego who conducted the work while at University of California, San Diego. But discovering how spores manage to track their environment while more dead than alive is an exciting start.

Super strong artificial silk? That’s so metal.

Giving revamped silkworm silk a metallic bath may make the strands both strong and stiff, scientists report October 6 in Matter. Some strands were up to 70 percent stronger than silk spun by spiders, the team found.

The work is the latest in a decades-long quest to create fibers as strong, lightweight and biodegradable as spider silk. If scientists could mass-produce such material, the potential uses range from the biomedical to the athletic. Sutures, artificial ligaments and tendons — even sporting equipment could get an arachnid enhancement.
“If you’ve got a climbing rope that weighs half of what it normally does and still has the same mechanical properties, then obviously you’re going to be a happy climber,” says Randy Lewis, a silk scientist at Utah State University in Logan who was not involved with the study.

Scrounging up enough silky material to make these super strong products has been a big hurdle. Silk from silkworms is simple to harvest, but not all that strong. And spider silk, the gold-standard for handspun strength and toughness, is not exactly easy to collect. “Unlike silkworms, spiders cannot be farmed due to their territorial and aggressive nature,” write study coauthor Zhi Lin, a structural biologist at Tianjin University in China, and colleagues.

Scientists around the world have tried to spin sturdy strands in the lab using silkworm cocoons as a starting point. The first step is to strip off the silk’s gummy outer coating. Scientists can do this by boiling the fibers in a chemical bath, but that can be like taking a hatchet to silk proteins. If the proteins get too damaged, it’s hard for scientists to respin them into high-quality strands, says Chris Holland, a materials scientist at the University of Sheffield in England who was not involved in the study.

Lin’s team tried gentler approaches, one of which used lower temperatures and a papaya enzyme, to help dissolve the silk’s coating. That mild-mannered method seemed to work. “They don’t have little itty-bitty pieces of silk protein,” Lewis says. “That’s huge because the bigger the proteins that remain, the stronger the fibers are going to be.”
After some processing steps, the researchers forced the resulting silk sludge through a tiny tube, like squeezing out toothpaste. Then, they bathed the extruded silk in a solution containing zinc and iron ions, eventually stretching the strands like taffy to make long, skinny fibers. The metal dip could be why some of the strands were so strong — Lin’s team detected zinc ions in the finished fibers. But Holland and Lewis aren’t so sure.

The team’s real innovation may be that “they’ve managed to unspin silk in a less damaging way,” Holland says. Lewis agrees. “In my mind,” he says, “that’s a major step forward.”