Scientists have explained how one of the deadliest forms of bacteria gets past the body’s defenses.
Researchers at the University of Illinois at Urbana-Champaign and Newcastle University in the U.K. have discovered how Staphylococcus aureus can blunt the body’s key weapons in its fight against infection.
The researchers are investigating how infectious microbes can survive attacks by the body’s immune system, which could lead to a better understanding on the bacteria’s and new strategies that can cure infections that are currently resistant to treatments.
S. aureus is found on approximately half of the population and while it usually safely coexists with healthy individuals, it has the ability to infect nearly the entire body.
In its pathogenic form, the bacterium is the “superbug” methicillin-resistant S. aureus (MRSA), which would be increasingly difficult, if not impossible to stop, with the emergence and spread of antibiotic-resistant bacteria.
Leading health organizations, such as the Centers for Disease Control and Prevention and the World Health Organization, have been prompted to issue an urgent call for new approaches to combat the threat of antibiotic resistance.
University of Illinois microbiology professor Thomas Kehl-Fie, Ph.D., who led the study with Kevin Waldron, Ph.D., university research fellow at Newcastle University, said that the human body uses a variety of weapons to fight off bacteria.
“Pathogens such as S. aureus have developed ways to subvert the immune response,” Kehl-Fie said.
S. aureus is able to overcome one of the body’s key defenses—nutritional immunity—which prevents bacteria from obtaining critical nutrients. Nutritional immunity starves S. aureus of Manganese, a metal needed by the bacterial enzyme superoxide dismutase.
This enzyme functions as a shield and minimizes the damage from another weapon in the body’s arsenal, the oxidative burst.
S. aureus is able to cause infections because it possesses two SOD enzymes, differing from other closely related species. The second SOD enhances the ability of the bacteria to resist nutritional immunity and cause disease.
“This realization was both exciting and perplexing, as both SODs were thought to utilize manganese and therefore should be inactivated by manganese starvation,” Kehl-Fie said.
The most prevalent family of SODs come in two varieties—those that are dependent on manganese for function and those that use iron.
The team tested whether the second staphylococcal SOD was dependent on iron and discovered that the enzyme was able to use either metal, much to the surprise of scientists.
Scientists have been aware of the existence of cambialistic SODs for several decades, but the existence of this type of enzyme was largely dismissed as a quirk of chemistry and unimportant in real biological systems.
However, the recent research dispels this notion, demonstrating that cambialistic SODs critically contribute to infection.
The science team found that when starved of manganese by the body, S. aureus activated the cambialistic SOD with iron instead of manganese.
This ensures that the critical bacterial defensive barrier was maintained.
“The cambialistic SOD plays a key role in this bacterium’s ability to evade the immune defense,” Waldron said in a statement. “Importantly, we suspect similar enzymes may be present in other pathogenic bacteria.
“Therefore, it could be possible to target this system with drugs for future antibacterial therapies.”
The study was published in PLOS Pathogens.