Fighting Infections
With a New Approach

LSU researchers are pioneering a new antibiotic approach to outsmart resistant bacteria and save lives worldwide.

A routine surgery. An infection after a hospital stay. Antibiotics have long been the invisible safety net that keeps these everyday risks from turning life-threatening. But that safety net is fraying. 

Across the world, bacteria are evolving faster than medicine can keep up. Antibiotic resistance is growing, and once-powerful drugs are losing their punch.


“Many things that can be done in modern medicine rely on antibiotics, but if our antibiotics do not work, then medicine ceases to be what it is now.”

— LSU Professor Mario Rivera 

Without new solutions, minor injuries or common illnesses could once again put lives at risk, especially for the very young, the very old, and the most vulnerable populations. 

At LSU, Department of Chemistry Professor Mario Rivera and his cross-disciplinary research team are trying to find a new class of antibiotics that focuses on a different part of bacteria physiology untouched by existing antibiotics. 

1M+

Deaths attributed to antibiotic resistance every year around the world.

$4.6B

Annual U.S. cost in care and lost productivity due to drug-resistant bacterial infections.

Rivera’s research is trying to block a process called bacterial iron homeostasis, which is how bacteria manage their iron supply, starving bacteria of the iron they require for life.

 

 

 

Potential New Weapon in the 'War With Bacteria'

Both humans and bacteria require iron for life. Bacteria have evolved to steal the iron they need from their host human.

“The immune system is conducting a chemical war with bacteria trying to set an infection,” Rivera said. “By interfering with bacteria’s ability to fight for iron (iron mobilization), the hope is that this novel approach can kill bacteria and help the immune system do its job.”

The bacterioferritin molecule exists in bacteria, but not in humans. Rivera describes it as a “soccer-ball-type” molecule, with a hollow interior where thousands of iron ions can accumulate and be mobilized back into the bacterial solution called cytosol for the bacteria’s use.

Rivera and his collaborators have developed compounds that can bond to bacterioferritin and block that mobilization so that the bacteria can’t access its iron reserves, leading to the death of the bacteria.

 

 

 

 

 

 

A Short History of How We Got Here

Before antibiotics, a simple cut could result in serious infection and sometimes death. The introduction of antibiotics, many of which were discovered in the 1940s and 1950s, was a game-changer.

Over the years, bacteria have developed resistance to antibiotics, requiring researchers to modify and make small tweaks to the structures of existing antibiotics to gradually overcome some of the resistance. But that has become more and more difficult, and now it's difficult to keep doing tweaks on antibiotics and keep overcoming resistance.

Antibiotic discovery had long been the purview of pharmaceutical companies, but Rivera said that is no longer the case, as those companies have divested from antibiotic discovery for return-on-investment and other economic and regulatory reasons.

“Antibiotic discovery has really shifted to academic institutions. And so that's important to understand,” he said. “If the public can support, for example, the idea of funding for infectious diseases, for discovering antibiotics, that helps  academic institutions contribute to the mission.”

 

 

 

Textbook Example: Diabetes

In 2023, close to half a million people in Louisiana were diagnosed with diabetes, with an estimated 100,000 more undiagnosed, according to the American Diabetes Association.

Diabetes patients often develop foot ulcers where bacteria are embedded in a matrix of their own making called biofilms that give bacteria added protection. Because the bacteria in biofilms are tolerant of existing antibiotics, this can lead to chronic infections that existing antibiotics cannot treat.

"However, if we treated the bacteria with the compounds that we are developing, we could kill bacteria in the biofilm. And so that was very exciting, and so we're pursuing that,” Rivera said.

The potential impact of that research could be game-changing, improving outcomes of diabetes patients and others both in Louisiana and around the world.

Rivera said one of the most exciting things about this research is that its origins can be traced to fundamental curiosity.

Interest in the bacterioferritin molecule led to research to see how the molecule behaved in the laboratory and, eventually, a realization of its potential as a target for a new type of antibiotics. 

“It's basically from fundamental knowledge that we started to develop potentially important applications. That's exciting for me,” Rivera said. “The other exciting thing is that we're training students in these areas. And when they move on to bigger things, hopefully they will carry with them this idea that it's important to innovate from the ground up.” 

Alex Behm, a doctoral degree candidate in chemistry at LSU, said collaboration in the lab allows the team as a whole to make more impact. 

“It takes like-minded individuals and individuals who want to make a difference and improve their academic career. And then everybody can collaborate and be together and make something bigger.”

Mario Rivera

Mario Rivera is a professor at LSU’s Department of Chemistry in the College of Science.

“Discovery of new antibiotics is a world of creativity, and I think that creativity begets creativity. As we see new, innovative things being done, I think it just spurs us to think about other things that we can do.”

— Dr. George Karam, LSU School of Medicine in New Orleans, Baton Rouge Regional Campus 

The stakes couldn’t be higher, Rivera said. Without effective antibiotics, procedures like surgery, cancer treatment, and organ transplants would become more dangerous.

Dr. George Karam of the LSU School of Medicine in New Orleans, Baton Rouge Regional Campus, said the costs of antibiotic resistance often fail to account for lost income and complications of long-term care, which can go well beyond treatment costs.

LSU alum Julie Viator, who has battled a chronic lung infection called Mycobacterium avium complex (MAC) since 2011, has also experienced a different kind of cost. The infection’s resistance to antibiotics limits her active lifestyle and requires constant monitoring for a possible recurrence.

“The hardest part is knowing that it’s gonna come back,” she said. “I’m in remission right now, but I know that can change in an instant.” She uses a football analogy that she’s almost to the recovery goal line but not quite there.

“So I’m very excited about this research because I think it will put me and others like me into the end zone.”

Dr. George Karam

Dr. George Karam holds the Paula Garvey Manship Endowed Chair for Medical Education at the LSU School of Medicine in New Orleans, Baton Rouge Regional Campus.

 

Gloved hands holding petri dishes in lab

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