Bacteria Versus Bacteria: A New Approach to Antibiotic-resistant Pathogens

As health experts continue to tackle the problem of antibiotic-resistant bacteria, a team of researchers in the United Kingdom has investigated a new bacteria-versus-bacteria approach to fighting dangerous pathogens.

New approaches and novel drugs designed to take on bacteria resistant to antibiotics continue to emerge and offer new fronts in the battle against deadly infections. Still, the World Health Organization (WHO) calls antibiotic resistance one of the biggest threats to global health, food security, and development. Around the world, resistant forms of tuberculosis, pneumonia, and gonorrhea have become harder to treat, and thus, more likely to kill those infected. While health officials call for judicious antibiotic use and the development of new antibiotics to prevent and treat virulent bacterial infections, pathogens continue to develop new resistance mechanisms faster than researchers can outsmart them.

Researchers at the Imperial College of London and Nottingham University Medical School in the UK recently studied a novel approach to treating multidrug-resistant shigellosis infections. Caused by the Shigella group of bacteria, these intestinal infections typically lead to diarrhea, fever, and stomach cramps within a day or two of exposure to the pathogen and symptoms can last for up to a week. Shigella is one of several bacteria associated with traveler’s diarrhea, particularly for those traveling to parts of Africa, Central America, South America, and Asia.

Since 2013, the Centers for Disease Control and Prevention (CDC) in the United States has considered antibiotic-resistant Shigella as an urgent threat, with forms of the bacteria becoming increasingly resistant to first-line antibiotics such as ampicillin and trimethoprim-sulfamethoxazole. Cases of shigellosis infections resistant to the commonly used antibiotics, ciprofloxacin or azithromycin, though a bigger problem in developing countries, are appearing more frequently in the United States. While estimates vary on the number of shigellosis-related deaths occurring worldwide each year, a recent CDC advisory on travel-related health threats projects that 80 million to 165 million Shigella infections each year lead to 600,000 annual deaths.

In the new study from the UK research team, published in the journal Current Biology, researchers conducted an experiment using Bdellovibrio bacteriovorus, a naturally occurring predatory bacterium, to fight Shigella bacteria. Predatory Bdellovibrio in natural environments are known to kill gram-negative bacterial pathogens and past studies have looked into the potential use of these bacteria as an antimicrobial agent. In their investigation, the researchers studied zebrafish larvae infected with a lethal dose of an antibiotic-resistant strain of Shigella flexneri, injecting them with Bdellovibrio as an antibacterial. In uninfected larvae, the predatory bacteria can live but is not pathogenic. In the infected larvae, the team found that Bdellovibrio work to reduce the number of Shigella, increasing the larvae’s chances for survival.

"This study really shows what a unique and interesting bacterium Bdellovibrio is as it presents this amazing natural synergy with the immune system and persists just long enough to kill prey bacteria before being naturally cleared,” said co-lead author and Imperial College London researcher Serge Mostowy, PhD, co-lead author from Imperial College London, in a recent press release. “It’s an important milestone in research into the use of a living antibiotic that could be used in animals and humans."

In their study, the authors note that Bdellovibrio worked with the hosts’ own immunity to impart full therapeutic benefits. Bdellovibrio live in a host long enough to prey on pathogens and can be engulfed and ultimately eliminated by a host’s neutrophils and macrophages. “This has been a truly ground-breaking collaboration that shows therapeutic Bdellovibrio in action inside the translucent living zebrafish,” said co-lead author and University of Nottingham professor Liz Sockett, PhD. “The predatory action of the Bdellovibrio breaks the Shigella-pathogen cells and this stimulates the white blood cells; redoubling their ‘efforts’ against the pathogen and leading to increased survival of the zebrafish ‘patients.’"

The authors conclude that using Bdellovibrio bacteria as active antibacterial predators can be a beneficial approach to treating drug-resistant infections. With continued experiments they hope to better understand the “host immune response to this therapy, determine ways to modify predatory bacteria with immune-stimulatory properties, and examine the use of Bdellovibrio in more prolonged infections.”