Bacterial defence systems could help with new vaccines

Like a well-trained soldier with honed survival skills, the common bacterium, Group A Streptococcus (GAS), sometimes can endure battle with our inborn (innate) immune system and cause widespread disease. By investigating the ability of combat-ready white blood cells (WBCs) to ingest and kill GAS, researchers have discovered new insights into how this disease-causing bacteria can evade destruction by the immune system.

Some GAS infections may be asymptomatic, and if untreated, can lead to life-threatening infections. With an early diagnosis, however, noninvasive GAS can be successfully treated with antibiotics. On the other hand, it is much more difficult to treat invasive GAS disease, and these infections are associated with high morbidity and mortality.

By examining the interaction between disease-fighting human white blood cells (WBCs) and a type of GAS that causes abundant disease in North America and Western Europe, the scientists have discovered how GAS elicits its own genome-wide protective response to evade destruction by the human immune system.

For their study, the researchers used human WBCs called polymorphonuclear leukocytes (PMNs), an essential component of the immune system's defense against foreign invaders. These microbe-eating cells are in a class of cells termed phagocytes, which stand ready to seek and destroy foreign substances such as bacteria. During battle with most foreign microbes, PMNs successfully "eat" invading predators, a scientific process called phagocytosis.

After microbes are engulfed, PMNs produce deadly oxygen radicals, such as hydrogen peroxide and hypoclorous acid and release toxic granules to kill the enemy. Normally, this defense tactic can defeat most foreign invaders, but it is ineffective against highly evolved GAS bacterium.

The scientists examined how PMNs from healthy individuals ingest and kill GAS and tested their hypothesis that GAS revs up or slows down the production of specific factors to evade the innate immune system.

The study indicates that GAS becomes more resilient to ingestion and killing by PMNs over time or it produces factors that alter normal PMN function. This resiliency is demonstrated by the increased expression of various GAS genes associated with the bacteria's virulence and cell wall repair as well as genes that encode proteins likely to promote immune evasion.

The scientists hope that this new knowledge in combination with their earlier GAS research will lead to further investigation of how GAS evades destruction by our innate immune system and will inevitably spur the discovery of vaccine therapies and antibiotics that can prevent and treat invasive and noninvasive strains of this bacterium.