ULSAN — Researchers have found that the attack power of predatory bacteria that feed on antibiotic-resistant microbes varies with the surface structure of their prey. The finding is expected to provide a starting point for developing "living antimicrobials" that improve treatment outcomes by selecting predatory bacteria matched to the traits of a given pathogen.
The Ulsan National Institute of Science and Technology (UNIST) said on the 22nd that a team led by Professor Robert Mitchell of the Department of Biological Sciences has determined that the structure of lipopolysaccharide (LPS), a component of the outer membrane of E. coli, governs the attack efficiency of the predatory bacterium Bdellovibrio bacteriovorus.
Bdellovibrio invades the interior of gram-negative pathogens, breaks down the host's cytoplasmic components to multiply, and then destroys the host. It can eliminate even resistant bacteria that no longer respond to existing antibiotics, and it degrades the host's genetic material, blocking the spread of resistance genes. But it had not been clearly established which surface structures are involved when the bacterium recognizes and penetrates a host surface.
The team focused on the lipopolysaccharide sugar chains that extend from the outer membrane of gram-negative bacteria. Using genetic engineering, the researchers removed the LPS synthesis genes of E. coli one by one and compared the attack performance of four Bdellovibrio strains.
The experiments showed that the shorter the "inner core" — the sugar chain closest to the outer membrane — the more the initial attack was delayed for all four strains. The more the chain was truncated, the more E. coli survived, and the lower the rate at which hosts formed "bdelloplasts," the rounded shape they take on after the bacterium invades. When the deleted genes were restored, E. coli again became vulnerable to predation.
Conversely, attack efficiency also fell for two of the strains when a long sugar chain known as the "O antigen" was added to the end of the chain. The long sugar chain masked the surface structures that the predatory bacterium needs for attachment and penetration. The other two strains, however, were not greatly affected by the O antigen, meaning that each strain differs in its ability to recognize host surfaces or overcome obstacles.
Based on these results, the team proposed a "Goldilocks LPS structure" model. The explanation is that attack is most effective when the inner core, the foundational structure of the lipopolysaccharide, is intact while the outer long chains do not excessively block access to the surface.
The researchers also identified conditions that artificially raise attack power. When the predatory bacteria were cultured for one hour in a solution containing E. coli lipopolysaccharide and then mixed with E. coli, they killed the E. coli faster than when no pretreatment was given. The team plans to conduct further research to identify the specific mechanism by which pre-exposure heightens attack activity.
"To use predatory bacteria as an antimicrobial tool, we need to know how well they attack the target pathogen and what determines their effectiveness," Mitchell said. "This study will serve as basic data for selecting bacteria suited to a pathogen's surface structure and for finding conditions that increase attack activity."
The research was supported by the Korea National Institute of Health under the Ministry of Health and Welfare, the National Research Foundation of Korea under the Ministry of Science and ICT, and the U.S. Air Force Office of Scientific Research. The findings were published online on Sept. 14 in The ISME Journal, an international journal in the field of microbial ecology.