Unveiling the Paradox: How Specific Antibodies Fuel the Virulence of Group A Streptococci

Group A streptococci (GAS) are a type of bacteria that can cause various human diseases, making them an important pathogen to understand. GAS is responsible for common infections such as strep throat, tonsillitis, and impetigo, which are highly contagious and can spread through respiratory droplets or direct contact with infected individuals. However, GAS can also lead to more severe and invasive infections, including cellulitis, necrotizing fasciitis, and toxic shock syndrome. These invasive infections occur when GAS enters deeper tissues or the bloodstream, requiring urgent medical attention. If left untreated, they can be life-threatening, causing severe tissue damage, organ failure, or sepsis. Additionally, GAS infection is associated with rheumatic fever, an autoimmune condition resulting from an abnormal immune response to certain strains of Group A streptococci. If untreated, rheumatic fever can damage the heart valves, leading to rheumatic heart disease, which can be debilitating and fatal.

One of the key factors that contribute to the virulence of GAS is the M protein. This protein is located on the surface of the bacteria and plays multiple roles in bacterial pathogenesis. The M protein can bind to various host molecules, including fibrinogen, complement factors, and immunoglobulins, modulating their activities. Additionally, the M protein can bind to fibronectin, an extracellular matrix protein found in various host tissues and cells. This interaction between M protein and fibronectin is known to facilitate bacterial adherence to host cells.

When a person is infected with GAS, their immune system produces specific antibodies against the M protein in response to the infection. These antibodies can opsonize the bacteria, promoting their clearance by phagocytes. However, some studies have suggested that specific antibodies may also have detrimental effects on the host defense against GAS infection. For example, they may interfere with the binding of complement factors to M protein, reducing their opsonic activity. The effect of specific antibodies on the M protein-fibronectin interaction and its consequences for bacterial adherence and pathogenesis have not been extensively studied.

A recent study conducted by researchers from Lund University, led by Associate Professor Pontus Nordenfelt, shed light on the interaction between specific human antibodies and GAS. The study, published in the peer-reviewed journal Frontiers in Microbiology, demonstrated that specific human antibodies bound to group A streptococci actually enhanced the M protein-fibronectin interaction, leading to decreased phagocytosis by immune cells. This finding reveals a novel mechanism by which GAS circumvents the host immune response to potentially to avoid the immune response. Surprisingly, the antibodies that are normally produced to protect the host from bacterial invasion  showed reduced phagocytic uptake of GAS into host immune cells when fibronectin was present. This may partially explain why group A streptococcal infections are often recurrent and persistent despite the presence of specific antibodies in the host.

The researchers also found that the enhanced M protein-fibronectin interaction mediated by specific human antibodies was independent of other serum or plasma components. This implies that the enhancement is not due to a nonspecific effect of serum or plasma proteins but rather a specific interaction between the Fab region of the antibodies and the M protein.

These findings provide new insights into the pathogenesis of group A streptococcal infections. Future research efforts can focus on developing interventions that specifically target the M protein-fibronectin interaction or block the detrimental effects of specific human antibodies, aiming to combat these infections more effectively.

In conclusion, the study conducted by Professor Pontus Nordenfelt and colleagues demonstrated that specific human antibodies bound to group A streptococci enhance the M protein-fibronectin interaction, resulting in a reduced phagocytosis of bacteria. This finding uncovers a novel mechanism by which group A streptococci exploit the host immune response to facilitate their protection from clearance by phagocytes. These insights provide a foundation for further research and potential strategies to prevent and treat these infections effectively.