Breakthrough Antimicrobial Discovery Offers Hope in Fight Against Cholera

Researchers at The University of Texas at Austin have discovered a new class of antimicrobials, microcins, that target the strains of bacteria causing cholera. This breakthrough offers hope in treating antibiotic-resistant infections and improving gut health.

Researchers at The University of Texas at Austin have made a groundbreaking discovery that could change the landscape of disease treatment and prevention. In two recent studies, they have identified a new class of natural antimicrobials, called microcins, which show potential in fighting harmful pathogens such as those causing cholera.

Cholera, a severe diarrheal disease caused by the Vibrio cholerae bacteria, can lead to rapid dehydration and death within hours. According to the World Health Organization, cholera claims between 21,000 and 143,000 lives each year worldwide. The quest for effective treatments has been urgent, particularly in an era where antibiotic resistance is on the rise.

In a study published in Cell Host & Microbe, UT Austin researchers, led by doctoral candidate Sun-Young Kim, have pinpointed the first known microcin that targets cholera-causing bacteria. This discovery is significant not only for its immediate implications for cholera but also for its broader potential to treat other serious health conditions like pathogenic E. coli infections, inflammatory bowel disease and colon cancer.

“Imagine one day eating yogurt containing probiotic strains of bacteria that produce microcins to prevent or treat cholera, pathogenic E. coli, inflammatory bowel disease or colon cancer,” Bryan Davies, professor of molecular biosciences and a senior author on both papers, said in a news release. “The idea is to put in healthy bacteria that would then be able to continually make microcins in the gut to fight off the pathogen of interest.”

Microcins are unique in that they specifically target harmful bacteria without disturbing the beneficial bacteria within the human gut microbiome. This selectivity could make them highly effective in treating infections while preserving the delicate balance essential for overall health. Additionally, microcins operate through a different mechanism than traditional antibiotics, offering a promising solution against antibiotic-resistant bacteria.

To discover these microcins, the research team employed artificial intelligence. They developed an AI-based approach utilizing protein large language models (LLMs), akin to the technology behind modern chatbots like ChatGPT, to scan bacterial genomes for potential candidates.

This innovative method, described in a forthcoming peer-reviewed paper, has already revealed about two dozen candidate microcins from nonpathogenic strains of V. cholerae. One such microcin, MvcC, has proven effective in killing pathogenic V. cholerae strains.

“You have bacteria in your gut right now making microcins,” Davies added. “They’re a natural part of how your bacterial communities organize and compete.”

The researchers also uncovered that microcin-producing V. cholerae bacteria possess a built-in “antidote” known as an immunity protease, which prevents them from being harmed by their own microcins. In experiments with mice, the microcin-producing bacteria successfully outcompeted the pathogenic strains, illustrating their potential as a natural defense mechanism.

The implications of this research are profound. By harnessing the power of microcins, we could develop new probiotic treatments not just for cholera, but for a range of gut-related diseases. This breakthrough has the potential to save lives and shift the paradigm in our ongoing battle against antibiotic-resistant pathogens.

“Microcin biology is very unique and extremely understudied,” Claus Wilke, a UT professor of integrative biology and statistics and data sciences and a co-author on the forthcoming paper, said in the news release. “And so, it’s a good field to be in, where there’s still a lot to be done and to be discovered.”