Science
A potent antibiotic has emerged in the battle against deadly, drug-resistant superbugs
Under a microscope, this drug-resistant superbug looks as benign as a handful of pebbles. Yet carbapenem-resistant Acinetobacter baumannii, or CRAB, is a nightmare for hospitals worldwide, as it kills roughly half of all patients who acquire it.
Identified as a top-priority pathogen by both the World Health Organization and the U.S. Centers for Disease Control and Prevention, CRAB is the most common form of a group of bacteria that are resistant to nearly all available antibiotics. Victims are typically hospitalized patients who are already sick with blood infections or pneumonia. In the U.S. alone, the bug sickens thousands and kills hundreds every year.
But 2024 is starting with some encouraging news on the global health front: For the first time in half a century, researchers have identified a new antibiotic that appears to effectively kill A. baumannii.
The compound, zosurabalpin, attacks bacteria from a novel angle, disrupting the route that a key toxin takes on its journey from inside the bacterial cell to the outer membrane that shields the bug from the immune system’s defensive onslaughts.
No other antibiotic approved by the U.S. Food and Drug Administration takes this approach, and the element of surprise is an important advantage against even microscopic foes. A. baumannii has had no opportunity to develop resistance against the drug, which means that, for at least a little while, zosurabalpin could ward off severe illness and death.
“As far as I can tell, the scientific approach is brilliant,” said Dr. Oladele A. Ogunseitan, a professor of population health and disease prevention at UC Irvine who was not involved with the study.
The drug was developed jointly by scientists at the Swiss pharmaceutical company Roche and at Harvard University. Their findings were published Wednesday in the journal Nature.
Carbapenem-resistant A. baumannii is a type of Gram-negative bacteria, a vexing category of superbugs. Encased in both an inner and outer membrane that antibiotics struggle to cross, Gram-negative bacteria are resistant to most currently available therapies. They are also astonishingly canny for unicellular organisms, with the ability to rapidly develop new defenses against antibiotics and then pass them along to other bacteria through genetic material.
Antibiotic-resistant superbugs claim the lives of more than 1 million people globally each year. The rise of drug resistance is due in part to human folly — we have long over-prescribed and misused antibiotics — but it is also because bacteria are continually finding ways to evade threats. Over the last 50 years, these pathogens have evolved defenses faster than we can produce new drugs.
In their search for a new weapon, the Roche and Harvard scientists turned their attention to a group of compounds called tethered macrocyclic peptides. After testing a library of 45,000 MCPs, the researchers came across one that seemed especially lethal against A. baumannii. After some chemical tinkering, that compound became zosurabalpin.
“This is a very promising advance,” said Paul J. Hergenrother, a chemistry professor at the University of Illinois who was not involved in the research but wrote of the findings for Nature. “Zosurabalpin kills bacteria in a way that is different from all other approved antibiotics.”
The drug kicks into gear only in the presence of lipopolysaccharide, a bacterial toxin. LPS is made inside the bacterial cell and is carried by a dedicated transport system to the bug’s outer defenses.
“The bacterial outer membrane is important for bacteria because it helps them to live in harsh conditions and to survive attacks by our immune system,” said Kenneth Bradley, Roche’s global chief of discovery for infectious diseases.
Zosurabalpin essentially cuts off the LPS transport route. Without a way to get to the outer membrane of the cell, where it can get to work fighting off drugs and immune attacks, the toxin builds up inside the bacteria and eventually kills the cell.
In mice studies, the drug effectively killed off CRAB infections in the blood, lungs and thighs, a selection that mirrors the ways the bug infects humans.
It’s currently in Phase I trials in humans, where researchers are looking at the drug’s safety, tolerability and the amount of the chemical that remains in patients’ bodies over time, said Michael Lobritz, Roche’s infectious disease chief.
“It has been more than 50 years since the last distinct class of antibiotic was launched that is capable of treating infections by Gram-negative bacteria,” Lobritz said in an email. “Any new antibiotic class that has the ability to treat infections caused by multidrug resistant (MDR) bacteria such as carbapenem-resistant Acinetobacter baumannii (CRAB) would be a significant breakthrough.”
Encouraging as the early results are, scientists stressed that it would be foolish to get cocky in the fight against a bug that, time and time again, has found ways to evade our most advanced pharmaceutical weaponry.
“Resistance has emerged to every antibiotic ever created, and it is likely that resistance will emerge to zosurabalpin in the future too, if it successfully becomes a clinical antibiotic,” Bradley said.
In their findings, the authors noted a few gene mutations in the lab that significantly decreased the drug’s success against A. baumannii. These were rare but worrying; one freak mutation reduced the drug’s effectiveness 256-fold.
“Although the rates of appearance of these resistant organisms is low, and comparable to standard-of-care antibiotics, the observation affirms the principle that we can never rest on our laurels with the chemical and biochemical warfare that we are waging on bacterial pathogens,” Ogunseitan said.
Zosurabalpin is essentially unknown to bacteria. If it proves safe and effective in humans, there’s likely a limited window in which it could effectively spare lives and suffering. But no matter how sophisticated our tools, scientists said, these potentially deadly cells will always have a major advantage against us.
“Bacteria have a big numbers advantage — billions can be in a flask,” said Hergenrother. “Bacteria will eventually evolve resistance to virtually every antibiotic, which is why we need a steady supply of new antibiotic candidates.”
Science
Cluster of farmworkers diagnosed with rare animal-borne disease in Ventura County
A cluster of workers at Ventura County berry farms have been diagnosed with a rare disease often transmitted through sick animals’ urine, according to a public health advisory distributed to local doctors by county health officials Tuesday.
The bacterial infection, leptospirosis, has resulted in severe symptoms for some workers, including meningitis, an inflammation of the brain lining and spinal cord. Symptoms for mild cases included headaches and fevers.
The disease, which can be fatal, rarely spreads from human to human, according to the U.S. Centers for Disease Control and Prevention.
Ventura County Public Health has not given an official case count but said it had not identified any cases outside of the agriculture sector. The county’s agriculture commissioner was aware of 18 cases, the Ventura County Star reported.
The health department said it was first contacted by a local physician in October, who reported an unusual trend in symptoms among hospital patients.
After launching an investigation, the department identified leptospirosis as a probable cause of the illness and found most patients worked on caneberry farms that utilize hoop houses — greenhouse structures to shelter the crops.
As the investigation to identify any additional cases and the exact sources of exposure continues, Ventura County Public Health has asked healthcare providers to consider a leptospirosis diagnosis for sick agricultural workers, particularly berry harvesters.
Rodents are a common source and transmitter of disease, though other mammals — including livestock, cats and dogs — can transmit it as well.
The disease is spread through bodily fluids, such as urine, and is often contracted through cuts and abrasions that contact contaminated water and soil, where the bacteria can survive for months.
Humans can also contract the illness through contaminated food; however, the county health agency has found no known health risks to the general public, including through the contact or consumption of caneberries such as raspberries and blackberries.
Symptom onset typically occurs between two and 30 days after exposure, and symptoms can last for months if untreated, according to the CDC.
The illness often begins with mild symptoms, with fevers, chills, vomiting and headaches. Some cases can then enter a second, more severe phase that can result in kidney or liver failure.
Ventura County Public Health recommends agriculture and berry harvesters regularly rinse any cuts with soap and water and cover them with bandages. They also recommend wearing waterproof clothing and protection while working outdoors, including gloves and long-sleeve shirts and pants.
While there is no evidence of spread to the larger community, according to the department, residents should wash hands frequently and work to control rodents around their property if possible.
Pet owners can consult a veterinarian about leptospirosis vaccinations and should keep pets away from ponds, lakes and other natural bodies of water.
Science
Political stress: Can you stay engaged without sacrificing your mental health?
It’s been two weeks since Donald Trump won the presidential election, but Stacey Lamirand’s brain hasn’t stopped churning.
“I still think about the election all the time,” said the 60-year-old Bay Area resident, who wanted a Kamala Harris victory so badly that she flew to Pennsylvania and knocked on voters’ doors in the final days of the campaign. “I honestly don’t know what to do about that.”
Neither do the psychologists and political scientists who have been tracking the country’s slide toward toxic levels of partisanship.
Fully 69% of U.S. adults found the presidential election a significant source of stress in their lives, the American Psychological Assn. said in its latest Stress in America report.
The distress was present across the political spectrum, with 80% of Republicans, 79% of Democrats and 73% of independents surveyed saying they were stressed about the country’s future.
That’s unhealthy for the body politic — and for voters themselves. Stress can cause muscle tension, headaches, sleep problems and loss of appetite. Chronic stress can inflict more serious damage to the immune system and make people more vulnerable to heart attacks, strokes, diabetes, infertility, clinical anxiety, depression and other ailments.
In most circumstances, the sound medical advice is to disengage from the source of stress, therapists said. But when stress is coming from politics, that prescription pits the health of the individual against the health of the nation.
“I’m worried about people totally withdrawing from politics because it’s unpleasant,” said Aaron Weinschenk, a political scientist at the University of Wisconsin–Green Bay who studies political behavior and elections. “We don’t want them to do that. But we also don’t want them to feel sick.”
Modern life is full of stressors of all kinds: paying bills, pleasing difficult bosses, getting along with frenemies, caring for children or aging parents (or both).
The stress that stems from politics isn’t fundamentally different from other kinds of stress. What’s unique about it is the way it encompasses and enhances other sources of stress, said Brett Ford, a social psychologist at the University of Toronto who studies the link between emotions and political engagement.
For instance, she said, elections have the potential to make everyday stressors like money and health concerns more difficult to manage as candidates debate policies that could raise the price of gas or cut off access to certain kinds of medical care.
Layered on top of that is the fact that political disagreements have morphed into moral conflicts that are perceived as pitting good against evil.
“When someone comes into power who is not on the same page as you morally, that can hit very deeply,” Ford said.
Partisanship and polarization have raised the stakes as well. Voters who feel a strong connection to a political party become more invested in its success. That can make a loss at the ballot box feel like a personal defeat, she said.
There’s also the fact that we have limited control over the outcome of an election. A patient with heart disease can improve their prognosis by taking medicine, changing their diet, getting more exercise or quitting smoking. But a person with political stress is largely at the mercy of others.
“Politics is many forms of stress all rolled into one,” Ford said.
Weinschenk observed this firsthand the day after the election.
“I could feel it when I went into my classroom,” said the professor, whose research has found that people with political anxiety aren’t necessarily anxious in general. “I have a student who’s transgender and a couple of students who are gay. Their emotional state was so closed down.”
That’s almost to be expected in a place like Wisconsin, whose swing-state status caused residents to be bombarded with political messages. The more campaign ads a person is exposed to, the greater the risk of being diagnosed with anxiety, depression or another psychological ailment, according to a 2022 study in the journal PLOS One.
Political messages seem designed to keep voters “emotionally on edge,” said Vaile Wright, a licensed psychologist in Villa Park, Ill., and a member of the APA’s Stress in America team.
“It encourages emotion to drive our decision-making behavior, as opposed to logic,” Wright said. “When we’re really emotionally stimulated, it makes it so much more challenging to have civil conversation. For politicians, I think that’s powerful, because emotions can be very easily manipulated.”
Making voters feel anxious is a tried-and-true way to grab their attention, said Christopher Ojeda, a political scientist at UC Merced who studies mental health and politics.
“Feelings of anxiety can be mobilizing, definitely,” he said. “That’s why politicians make fear appeals — they want people to get engaged.”
On the other hand, “feelings of depression are demobilizing and take you out of the political system,” said Ojeda, author of “The Sad Citizen: How Politics is Depressing and Why it Matters.”
“What [these feelings] can tell you is, ‘Things aren’t going the way I want them to. Maybe I need to step back,’” he said.
Genessa Krasnow has been seeing a lot of that since the election.
The Seattle entrepreneur, who also campaigned for Harris, said it grates on her to see people laughing in restaurants “as if nothing had happened.” At a recent book club meeting, her fellow group members were willing to let her vent about politics for five minutes, but they weren’t interested in discussing ways they could counteract the incoming president.
“They’re in a state of disengagement,” said Krasnow, who is 56. She, meanwhile, is looking for new ways to reach young voters.
“I am exhausted. I am so sad,” she said. “But I don’t believe that disengaging is the answer.”
That’s the fundamental trade-off, Ojeda said, and there’s no one-size-fits-all solution.
“Everyone has to make a decision about how much engagement they can tolerate without undermining their psychological well-being,” he said.
Lamirand took steps to protect her mental health by cutting social media ties with people whose values aren’t aligned with hers. But she will remain politically active and expects to volunteer for phone-banking duty soon.
“Doing something is the only thing that allows me to feel better,” Lamirand said. “It allows me to feel some level of control.”
Ideally, Ford said, people would not have to choose between being politically active and preserving their mental health. She is investigating ways to help people feel hopeful, inspired and compassionate about political challenges, since these emotions can motivate action without triggering stress and anxiety.
“We want to counteract this pattern where the more involved you are, the worse you are,” Ford said.
The benefits would be felt across the political spectrum. In the APA survey, similar shares of Democrats, Republicans and independents agreed with statements like, “It causes me stress that politicians aren’t talking about the things that are most important to me,” and, “The political climate has caused strain between my family members and me.”
“Both sides are very invested in this country, and that is a good thing,” Wright said. “Antipathy and hopelessness really doesn’t serve us in the long run.”
Science
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