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Researchers at La Trobe University have discovered how a strain of bacteria responsible for severe diarrhea uses molecular tools to damage and destroy gut cells, potentially leading to serious illness or death.
The study, published in Gut Microbes, reveals the three-dimensional structure of a potent toxin secreted by enteropathogenic E. coli (EPEC). The toxin, known as EspC, acts as an enzyme that dismantles the internal protein framework of epithelial cells lining the gut, allowing the bacteria to invade and cause infection.
Professor Begoña Heras, who co-led the study, emphasized the importance of understanding how this toxin functions in order to develop more targeted treatments against EPEC, especially given the growing issue of antibiotic resistance.
"Many E. coli strains, including EPEC, are becoming resistant to commonly used antibiotics," said Professor Heras. "This is concerning, especially considering that diarrheal illnesses still claim the lives of approximately 1.3 million children under the age of five each year due to dehydration and electrolyte loss."
She added that uncovering the structure and mechanism of this bacterial toxin brings researchers closer to developing therapies that can stop the disease without contributing to the growing problem of antimicrobial resistance.
E. coli encompasses more than five strains that damage intestinal cells in various ways. For example, Shiga toxin-producing E. coli (STEC), linked to recent spinach recalls, invades using a different mechanism. EPEC, the focus of this study, is the leading cause of diarrhea in infants and young children worldwide.
Currently, most E. coli infections are treated with broad-spectrum antibiotics, which can harm both harmful and beneficial bacteria in the gut. Complicating matters, E. coli can rapidly adapt and become resistant to many existing drugs.
Dr. Jason Paxman, who also co-led the study, highlighted the difficulty of treating E. coli infections today. "We're increasingly relying on last-resort antibiotics, and in some cases, there are no effective treatments left," he explained. "Even when new antibiotics are developed, they’re often reserved for critical use, as resistance can emerge in just a few years."
He noted that conventional antibiotics do not target specific pathogens, which can lead to widespread resistance across multiple bacterial species.
The research was carried out by a multidisciplinary team at La Trobe’s Institute of Molecular Science (LIMS) and the School of Agriculture, Biomedicine and Environment (SABE). Dr. Akila Pilapitiya, the study's first author, conducted the work as part of her Ph.D., and emphasized how critical cross-disciplinary collaboration was in determining EspC’s structure.
"While it was known that EspC was a toxin, little was understood about its structure or function," said Dr. Pilapitiya. "Our multidisciplinary approach allowed us to visualize how the toxin is built and how each component contributes to its activity."
This detailed structural insight lays the groundwork for the design of new, targeted drugs that could neutralize EPEC without harming beneficial gut bacteria.
Professor Heras expressed hope that this approach will inspire further advances in fighting bacterial diseases. "Our findings demonstrate how the fusion of different scientific disciplines can answer complex biological questions and support the development of more effective and precise therapies to protect human health."
The study, published in Gut Microbes, reveals the three-dimensional structure of a potent toxin secreted by enteropathogenic E. coli (EPEC). The toxin, known as EspC, acts as an enzyme that dismantles the internal protein framework of epithelial cells lining the gut, allowing the bacteria to invade and cause infection.
Professor Begoña Heras, who co-led the study, emphasized the importance of understanding how this toxin functions in order to develop more targeted treatments against EPEC, especially given the growing issue of antibiotic resistance.
"Many E. coli strains, including EPEC, are becoming resistant to commonly used antibiotics," said Professor Heras. "This is concerning, especially considering that diarrheal illnesses still claim the lives of approximately 1.3 million children under the age of five each year due to dehydration and electrolyte loss."
She added that uncovering the structure and mechanism of this bacterial toxin brings researchers closer to developing therapies that can stop the disease without contributing to the growing problem of antimicrobial resistance.
E. coli encompasses more than five strains that damage intestinal cells in various ways. For example, Shiga toxin-producing E. coli (STEC), linked to recent spinach recalls, invades using a different mechanism. EPEC, the focus of this study, is the leading cause of diarrhea in infants and young children worldwide.
Currently, most E. coli infections are treated with broad-spectrum antibiotics, which can harm both harmful and beneficial bacteria in the gut. Complicating matters, E. coli can rapidly adapt and become resistant to many existing drugs.
Dr. Jason Paxman, who also co-led the study, highlighted the difficulty of treating E. coli infections today. "We're increasingly relying on last-resort antibiotics, and in some cases, there are no effective treatments left," he explained. "Even when new antibiotics are developed, they’re often reserved for critical use, as resistance can emerge in just a few years."
He noted that conventional antibiotics do not target specific pathogens, which can lead to widespread resistance across multiple bacterial species.
The research was carried out by a multidisciplinary team at La Trobe’s Institute of Molecular Science (LIMS) and the School of Agriculture, Biomedicine and Environment (SABE). Dr. Akila Pilapitiya, the study's first author, conducted the work as part of her Ph.D., and emphasized how critical cross-disciplinary collaboration was in determining EspC’s structure.
"While it was known that EspC was a toxin, little was understood about its structure or function," said Dr. Pilapitiya. "Our multidisciplinary approach allowed us to visualize how the toxin is built and how each component contributes to its activity."
This detailed structural insight lays the groundwork for the design of new, targeted drugs that could neutralize EPEC without harming beneficial gut bacteria.
Professor Heras expressed hope that this approach will inspire further advances in fighting bacterial diseases. "Our findings demonstrate how the fusion of different scientific disciplines can answer complex biological questions and support the development of more effective and precise therapies to protect human health."