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New Antibiotic Fights Drug-resistant Bacteria To Stop Deadly Infections

Lariocidin, a new antibiotic, blocks bacterial protein production and defeats resistance without harming human cells. (CREDIT: Shutterstock)

A groundbreaking antibiotic discovery might finally tip the balance in the global fight against drug-resistant bacteria. Scientists have unveiled a rare molecule with a fresh way to stop dangerous infections—offering new hope after nearly 30 years without a new class of antibiotics.

A Soil Discovery Sparks New Hope

Deep within a simple backyard soil sample, researchers uncovered a rare bacterium that makes a powerful new compound. This compound, called lariocidin, is part of a group of unusual molecules known as lasso peptides. These molecules form a tiny knot-like shape that locks them into a rigid structure. This unique shape makes them more stable and more likely to survive long enough to fight harmful bacteria.

The research team at McMaster University, led by biochemistry professor Gerry Wright, discovered lariocidin from bacteria that had quietly grown in a lab for a year. "Bacteria aren't interested in making new drugs for us," Wright explained. "We let them grow slowly so even the shy ones had a chance to be seen." One species—Paenibacillus—produced something remarkable. It wasn't just killing other bacteria, it was doing so in a completely new way.

A new class of antibiotics has been identified by McMaster University researchers. (CREDIT: McMaster University)

This is a major achievement. Scientists haven't introduced a new antibiotic class into the market in decades. Now, with lariocidin, they have a chance to reshape the way medicine treats infections.

Lariocidin's Unique Battle Plan

Lariocidin works differently than most antibiotics. It doesn't simply damage a cell wall or block an enzyme. Instead, it targets the ribosome—the part of a bacterial cell that makes proteins. Proteins help bacteria grow, repair damage, and stay alive. When the ribosome breaks, bacteria can't make proteins and eventually die.

Lariocidin slips into a spot on the ribosome that no other drug has targeted. It binds to the small subunit of the ribosome and locks onto a stretch of genetic material called 16S rRNA, along with the aminoacyl-tRNA, which helps build proteins.

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This tight grip blocks the process of "translocation," where ribosomes move along the genetic code to build proteins. It also scrambles the genetic message, causing the bacteria to build the wrong proteins. This double hit—blocking movement and messing up the message—kills the cell.

"This is a new molecule with a new mode of action," said Wright. "It's a big leap forward for us."

Defeating Resistance with Smart Science

The biggest advantage of lariocidin is that bacteria haven't seen it before. That means they haven't developed defenses against it. Most antibiotics become less effective over time because bacteria find ways to fight back—a problem known as antimicrobial resistance, or AMR.

Gene composition of the lrc BGC. Bottom, post-translational modification of the LrcA precursor peptide leads to the production of LAR and its variants. (CREDIT: Nature)

AMR is a growing crisis. According to the World Health Organization, antibiotic resistance now causes about 4.5 million deaths each year. Old drugs fail more often, and fewer new ones are being developed to replace them. That's why this new antibiotic is getting so much attention.

Lariocidin avoids the traps that cause most drugs to fail. It resists common resistance mechanisms, doesn't trigger spontaneous resistance, and shows no signs of harming human cells. This means it could be safer and more effective than many antibiotics used today.

Manoj Jangra, a postdoctoral fellow on the team, said the moment they understood how lariocidin worked was unforgettable. "When we figured out how this new molecule kills other bacteria, it was a breakthrough moment."

The team also tested lariocidin's power in living organisms. In a mouse model infected with the highly resistant Acinetobacter baumannii—a bacteria often found in hospitals—lariocidin performed well, clearing the infection without causing harm to the animals. This result raised even more excitement about its potential use in people.

Structure of LAR in complex with the T. Thermophilus 70S ribosome. (CREDIT: Nature)

The Road Ahead: From Molecule to Medicine

Despite the excitement, bringing lariocidin to hospitals won't be fast or easy. Although nature made this molecule, scientists now have to figure out how to mass-produce it. "The initial discovery—the big a-ha! Moment—was astounding for us," Wright said. "But now the real hard work begins."

Making enough lariocidin for use in people will take years of testing and careful design. Researchers plan to tweak its structure to improve its strength, stability, and production. "We're now working on ripping this molecule apart and putting it back together again to make it a better drug candidate," said Wright.

Even small changes in the molecule can make a big difference in how well it works. The researchers want to keep the parts that kill bacteria but modify others to make the drug easier to produce and safer for human use.

Structures and electron density maps of ribosome-bound LAR and LAR-B. (CREDIT: Nature)

A Big Leap in the Antibiotic Fight

Lariocidin might become a key weapon in the war against resistant infections. Its discovery marks a rare moment in science where everything clicks—an unexplored soil bacterium, a molecule with a clever shape, and a completely new way to attack the ribosome. Its success in lab tests and animals shows that nature still holds answers to one of medicine's most urgent problems. By studying how bacteria fight each other in the wild, scientists might finally stay one step ahead of superbugs.

As the team at McMaster continues refining this promising compound, one thing is clear: new hope is growing, not in high-tech labs, but in soil, patience, and smart science.

Research findings are available online in the journal Nature.

Note: The article above provided above by The Brighter Side of News.

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Study Finds No Benefit From Early Antibiotics For Nonsevere COVID

A large observational study provides evidence that antibiotics provide no benefit for patients hospitalized with nonsevere COVID-19.

The study, published this week in JAMA Network Open, examined data on more than 520,000 US patients hospitalized for nonsevere COVID cases over a nearly 4-year period and found no clinically significant difference in outcomes between those who received antibiotics on day 1 of admission and those who didn't. In fact, patients who received antibiotics had slightly higher odds of poor clinical outcomes.

The authors of the study say the findings highlight the need for antibiotic stewardship strategies in patients admitted with nonsevere COVID-19.

High antibiotic use in COVID patients

Although COVID-19 is caused by a virus, at the beginning of the pandemic, more than 80% of hospitalized US COVID patients received antibiotics on admission, primarily because of limited treatment options and concerns about bacterial coinfections. There was also an early belief that azithromycin, in combination with hydroxychloroquine, might reduce COVID severity.

But retrospective data have since then shown that only 5% of COVID-19 patients had bacterial coinfections, and several randomized clinical trials have shown that azithromycin provides no benefit for COVID-19 patients. Once the first wave of COVID infections had passed and clinicians began using treatments like the antiviral drug remdesivir, monoclonal antibodies, and systemic steroids, antibiotic use in hospitalized COVID patients began to decline.

Even by the end of 2023, however, approximately 35% of US COVID patients were still receiving antibiotics on admission. The high rate of antibiotic prescribing in this population, combined with concerns about antibiotic resistance and potential patient harms from unnecessary antibiotic use, prompted researchers from the University of Wisconsin-Madison, the University of Massachusetts, and the University of Utah to assess clinical outcomes in hospitalized COVID patients who received antibiotics.

"When you look at the data and see that over 30% of COVID patients are still getting antibiotics, it's clear that they are still being widely utilized," lead study author Michael Pulia, MD, PhD, an emergency physician and associate professor at the University of Wisconsin-Madison School of Medicine and Public Health, told CIDRAP News. "So we have to get more data to show that it's either helpful or not."

When you look at the data and see that over 30% of COVID patients are still getting antibiotics, it's clear that they are still being widely utilized.

To do so, Pulia and his colleagues conducted a target trial emulation, which applies a randomized clinical trial framework to observational data in order to reduce the bias that typically occurs in observational studies. Using data from the Premier Healthcare Database, they identified adult, immunocompetent COVID-19 patients who were treated at US hospitals for COVID-19 from April 2020 through December 2023, excluding patients who had neutropenia, a non-pneumonia bacterial infection, or a chronic obstructive pulmonary disease (COPD) exacerbation. 

"As the name implies, we were trying our best to replicate with observational data the conditions that are present at the time that somebody would be enrolled in a prospective randomized trial," Pulia explained. "And we had good, robust ways of excluding a lot of the people that wouldn't typically be eligible for a trial."

The researchers then assessed outcomes in patients who received a community-acquired pneumonia (CAP) antibiotic regimen or no antibiotics on day 1 of hospitalization, using propensity methods and adjusting for potential confounders.

The primary outcome was a composite measure of patient deterioration (vasopressor, high-flow oxygen, noninvasive ventilation, invasive mechanical ventilation, intermediate care, intensive care unit admission) and in-hospital mortality occurring on day 2 or later. The researchers considered an absolute standardized difference (ASD) of greater than 10% as demonstrating clinically meaningful differences between the groups. 

No clinically meaningful difference in outcomes

A total of 520,405 patients (median age, 66 years; 51.2% male) treated at 1,053 US hospitals were included in the study. Of the patients, 160,482 (30.8%) were treated with a CAP antibiotic regimen on day 1 of admission. 

Patients treated with antibiotics were more likely to be Hispanic or other race or ethnicity and more likely to be treated at hospitals with fewer than 400 beds, hospitals in the South or West, rural hospitals, and non-teaching hospitals. Overall, 95,055 patients (18.3%) deteriorated and 22,355 (4.3%) died during their hospitalization. 

The analysis showed that the primary outcome was higher in the CAP group (20.8%) compared with the no-antibiotic group (18.4%), but the ASD (4.1%) did not meet the research team's predefined criteria for clinical significance. No clinically meaningful differences were found for secondary or safety outcomes.

But analysis of a matched cohort of 113,506 pairs using propensity score-weighted models found slightly higher odds of poor clinical outcomes associated with receipt of CAP antibiotics (propensity-matched odds ratio [OR], 1.03; 95% confidence interval [CI], 1.01 to 1.05; inverse probability treatment weighting OR, 1.03; 95% CI, 1.02 to 1.05; standardized mortality ratio weighting OR, 1.10; 95% CI, 1.08 to 1.12). 

Pulia characterized that finding as a slight signal toward harm, but he said the larger point is that antibiotics did not appear to help the patients who received them.

"We basically found nothing to suggest in any of our results that antibiotics would be beneficial at all on the outcomes we looked at," he said. And if there's no benefit, he added, then the adverse impacts of antibiotic use on patients and public health need to be considered.

In a commentary in the same journal, Sean Ong, MBBS, and Steven Tong, PhD, from the University of Melbourne, conclude, "Pulia and colleagues have demonstrated in their study an excellent example of how well-conducted observational research can fill existing research gaps where RCTs are lacking, and guide clinical decision-making." They add, however, that antibiotic therapy should be prescribed in COVID patients who were excluded from the analysis—such as those with COPD exacerbation—if there are clear indications for the drugs.

We basically found nothing to suggest in any of our results that antibiotics would be beneficial at all on the outcomes we looked at.

Pulia said that while prospective studies are needed, he hopes, at the very least, that the findings will make clinicians feel more comfortable in raising the threshold for initiating antibiotics in patients with nonsevere COVID, even if they are sick enough to be admitted to the hospital.

"Clearly the rate at which we're doing it today is too much," he said. "I think everybody's aware that it's a problem, it's just that it still happens a lot."

Roche Extends Trials Of Promising Antibiotic Against Resistant Superbug

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Swiss pharmaceutical company Roche is planning to move a new antibiotic into late stage clinical trials after early studies showed it had potential to tackle a common superbug that has become resistant to other treatments. 

If successful, it would be the first new class of antibiotic capable of killing acinetobacter or any other "Gram-negative" bacteria to be developed for more than 50 years. This type of bug has a structure that makes it more difficult to treat.

Roche will launch a phase 3 trial for zosurabalpin at the end of the year, or early next year. Acinetobacter can cause life-threatening infections including pneumonia and sepsis. Patients who are immunocompromised because of cancer or other serious diseases are particularly vulnerable. 

Larry Tsai, global head of immunology and product development at Genentech, a unit of Roche, and a pulmonary critical care physician, estimates that 40 to 60 per cent of acinetobacter infected patients die as a result of the bug. 

The trial will recruit about 400 patients at more than 100 sites worldwide, with the aim of getting the drug approved towards the end of the decade.   

Tsai said Roche was continuing its long legacy of developing new antibiotics "to ensure they are available as part of what we see as our societal commitment to global health security".

After a period when it withdrew from the field, about ten years ago Roche reinvested in tackling the growing problem of antimicrobial resistance, which the World Health Organization estimates could kill 10mn people a year by 2050.

Many drugmakers are reluctant to pursue new antibiotics because of a difficult market: the drugs are now used much more sparingly to try to prevent bacteria from building up resistance, meaning it can be hard to sell enough to cover the cost of research and development. 

Many smaller companies focused on developing antibiotics have struggled and some have closed. Tsai said that he understood the challenges first hand, having worked at a company with a promising antibiotic that still shut down. 

But he said there was increasing global recognition that antimicrobial resistance has been "neglected over the past few decades" and that health systems were attempting to change the incentives. 

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Policymakers have been searching for ways to encourage antibiotic development. The UK has adopted a model where drugmakers are paid an annual fee for making the medicines available, rather than for the volume used, while the US Congress has been discussing a similar model. 

Gram-negative bacteria are particularly hard to treat because they have a second outer membrane, creating a formidable barrier for drugs to cross. The last new class of antibiotics approved to treat Gram-negative bacteria was in 1968. 

Roche worked with researchers at Harvard to find a new way to kill the bacteria, weakening the cell's membrane by inhibiting a key component — a chemical called lipopolysaccharide — that boosts the membrane's resilience. 

Michael Lobritz, global head of infectious diseases at Roche Pharma research and early development, said looking for new classes of antibiotics involved "going back to the drawing board" and examining how bacteria work. Scientists can then build on new discoveries and potentially find other new antibiotics. 

"This antibiotic is important, but it can also serve as a catalysis point for future innovation. Finding new classes is very hard. There are very few . . . That have been discovered in the last 15 years. So if you are able to launch a new one, we can build off that for decades to come," he said.

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