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