Marquette researchers discover new probiotic to weaken multidrug-resistant staph infections, such as MRSA

Researchers in Marquette's Klingler College of Arts and Sciences have discovered a novel probiotic which can weaken the resistance of antimicrobial resistant bacterial infections, such as MRSA, by increasing its sensitivity to multiple antibiotics and inhibiting biofilm development in the human gut.

Dr. Krassimira Hristova, professor of biological sciences at Marquette, and her team identified a single probiotic strain-Bacillus subtilis 6D1-with potent ability to inhibit biofilm growth, disassemble mature biofilm and improve antibiotic sensitivity of staph infection biofilms by interfering with this pathogen's own communication system.

According to the World Health Organization, antimicrobial resistant bacterial infections accounted for an estimated 700,000 deaths worldwide in 2019, a number that is expected to surpass 10 million by 2050 if immediate measures are not taken. In the United States alone, 2.5 million AMR infections resulted in an estimated annual economic cost of more than $55 billion, warranting the need for new pathogen control measures to help combat this global health crisis.

"MRSA is one of the most clinically important pathogens in the world, with infections leading to high rates of disease and death in both humans and animals. Its ability to form biofilm increases this pathogen's ability to survive antibiotic treatment and cause disease," Hristova said. "We predicted that isolating potential probiotic strains from environments where frequent Staphylococcus aureus-or 'S. aureus'-interactions might occur would increase the likelihood of discovering probiotics with robust anti-staphylococcal activities. Our research findings exceeded our expectations in that we found a single strain with potent antibiofilm activity against S. aureus and were able to attribute this activity to small molecules that may serve as viable therapeutic options for the treatment of S. aureus-related infections."

Hristova published these findings in the American Society for Microbiology open-access journal, mSystems, on July 11 in a paper titled "Bacillus subtilis-derived peptides disrupt quorum sensing and biofilm assembly in multidrug-resistant Staphylococcus aureus." Her co-authors include Dr. Kyle R. Leistikow, former research microbiologist in Hristova's lab, and undergraduate researchers Nick Konopek and Grace Schmaling who contributed to the work. They also collaborated with Dr. Cameron Curie, professor of bacteriology, and his lab at the University of Wisconsin-Madison.

The primary goal of this research was to investigate novel antibiotic alternative therapies to help mitigate the disease-causing potential of the bacterial pathogen, S. aureus. The study showed that probiotic compounds produced by B. subtilis 6D1 could protect human gut epithelial cells from S. aureus infection by boosting these cells anti-inflammatory response, offering a promising alternative treatment strategy.

Hristova - recognized internationally for her research on the environmental dimensions of antimicrobial resistance and discovering beneficial microbes degrading harmful pollutants or helping to combat disease - offered a perspective on the significance of the study.

"This was a very surprising finding for us since it suggested that this unique probiotic strain may serve multiple roles in preventing S. aureus ability to cause disease including prompting human gut cells to initiate a beneficial immune response," Hristova said.

"There's still work to do, but our end goal is to commercially produce this strain and its unique compounds so that it can become more widely available to those suffering from these types of bacterial infections," Leistikow said.

Leistikow has over a decade of experience working as a researcher in the microbial biotechnology sector and is excited about the possibility of bringing this strain out of the lab and into the public's hands.

"Unlike traditional antibiotics that often force pathogens to adapt and become potential drug-resistant 'superbugs,' ongoing work with this probiotic has also shown that long-term exposure to these probiotic compounds does not make S. aureus more drug resistant," Leistikow said. "It's amazing to think that nature may have already developed tools to fight these superbugs; all we have to do is know where and how to look for these tools."

Hristova continues, "As a woman scientist, I am proud to contribute to finding drug alternative therapies. World Health Organization data tells us that women are disproportionately impacted by antibiotic resistant infections, and discovering natural tools like probiotics to fight these superbugs is a significant step forward in addressing this global public health issue."

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