Thursday, 13 February 2020

How the strep bacterium hides from the immune system


A bacterial pathogen that causes strep throat and other illnesses cloaks itself in fragments of red blood cells to evade detection by the host immune system, according to a new study. The researchers found that Group A Streptococcus (GAS) produces a previously uncharacterized protein, named S protein, which binds to the red blood cell membrane to avoid being engulfed and destroyed by phagocytic immune cells.


GAS is a human-specific pathogen that can cause many different infections, from minor illnesses to very serious and deadly diseases. Some of these conditions include strep throat, scarlet fever, a skin infection called impetigo, toxic shock syndrome, and flesh-eating disease. An estimated 700 million infections occur worldwide each year, resulting in more than half a million deaths. Despite active research, a protective vaccine remains elusive.

To date, penicillin remains a primary drug of choice for combatting GAS infections. But the rate of treatment failures with penicillin has increased to nearly 40% in certain regions of the world.


One alternative approach is to develop novel anti-virulence therapeutics. To avoid immune clearance, GAS expresses a wide variety of molecules called virulence factors to facilitate survival during infection. But the function of many of these proteins remains unknown, hindering the development of alternative pharmacological interventions to combat widespread antibiotic resistance.

To address this gap in knowledge, researchers used a nanotechnology-based technique called biomimetic virulomics to identify proteins that are secreted by GAS and bind to red blood cells. This approach revealed a previously uncharacterized protein, which the researchers named S protein, because this type of protein is limited to members of the Streptococcus genus.

The researchers found that a mutant bacterial strain lacking S protein was less able to grow in human blood, and less able to bind to red blood cells, compared to the non-mutated strain. The mutant strain was also more readily captured and killed by phagocytic immune cells called macrophages and neutrophils. In addition, the absence of S protein vastly reshaped the bacterial protein landscape, decreasing the abundance of many known virulence factors.
Moreover, mice infected with GAS cells coated with red blood cells showed a 90% mortality rate, compared to 40% of mice infected with uncoated GAS cells. Infection with coated GAS cells also caused a more rapid decrease in body weight.

Additional experiments showed that infection with GAS caused a progressive decline in the body weight of mice and a 90% mortality rate. By contrast, all mice infected with mutant GAS lacking S protein survived infection, and their body weight stabilized and remained constant after a slight initial decline. Infection with mutant GAS also resulted in a lower concentration of bacteria in the bloodstream and organs, and promoted a robust immune response and immunological memory.

See: Igor H. Wierzbicki, Anaamika Campeau, Diana Dehaini, et al. Group A Streptococcal S Protein Utilizes Red Blood Cells as Immune Camouflage and Is a Critical Determinant for Immune Evasion. Cell Reports, 2019; 29 (10): 2979 DOI: 10.1016/j.celrep.2019.11.001

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

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