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 study published in the journal Cell Reports. 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. By arming GAS with this form of immune camouflage, S protein enhances bacterial virulence and decreases survival in infected mice.
"Our study describes a completely novel mechanism for immune evasion," says corresponding author. "We believe the discovery of this previously overlooked virulence factor, S protein, has broad implications for development of countermeasures against GAS."
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. "Due to the high prevalence of GAS infection and the decreasing efficacy of the available set of countermeasures, it is critical to investigate alternative approaches against GAS infection," the senior author says.
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, the authors 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. "These findings suggest that S protein co-opts red blood cell membranes for molecular mimicry, or imitation of host molecules, to evade the immune response," the senior author says.
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.
"Taken together, the results suggest that inactivation of S protein function makes GAS vulnerable to host immunity," the senior author says. "S protein influences virulence by capturing lysed red blood cell membranes to cloak the bacterial cell surface, which allows bacteria to circumvent host immunity. This novel evasion mechanism can be targeted for anti-streptococcal therapies."
Currently, the team is examining the mechanism by which S protein binds to red blood cells. They are also studying the role that S protein plays in other important human pathogens, including Streptococcus pneumoniae, which causes pneumonia and other illnesses, as well as Group B Streptococcus or S. agalactiae--a bacterium that is a common cause of severe infections in newborns during the first week of life.
"Ultimately, the findings could lead to the development of a novel vaccine candidate," the senior author says. "Because of its pivotal roles in pathogenesis and immune evasion, and its conserved nature in Streptococci, S protein shows promising clinical potential as a target for the development of anti-virulence pharmacological interventions."
https://www.cell.com/cell-reports/fulltext/S2211-1247(19)31472-X
http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fgroup-a-streptococcal-s&filter=22
How the strep bacterium hides from the immune system
- 4,618 views
- Added
Edited
Latest News
Metabolic rewiring promotes…
By newseditor
Posted 18 Apr
A drug to prevent flu-induc…
By newseditor
Posted 18 Apr
New origin of deep brain waves
By newseditor
Posted 17 Apr
Starving cells hijack prote…
By newseditor
Posted 17 Apr
Miniature battery-free epid…
By newseditor
Posted 17 Apr
Other Top Stories
Motivation circuit in the mouse brain
Read more
Improving deep brain stimulation therapy for OCD
Read more
What are "Supermeres"?
Read more
Gene variants linked to severe schizophrenia identified!
Read more
Stem-cell based model for macular degeneration!
Read more
Protocols
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Modular dual-color BiAD sen…
By newseditor
Posted 31 Mar
Publications
How does the microbiota con…
By newseditor
Posted 18 Apr
The integrated stress respo…
By newseditor
Posted 18 Apr
The immunobiology of herpes…
By newseditor
Posted 17 Apr
Circulating microbiome DNA…
By newseditor
Posted 17 Apr
Spindle oscillations in com…
By newseditor
Posted 17 Apr
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar