The role of streptococcal nuclease SpnA in host interactions and response
(2025) MOBN03 20242Degree Projects in Molecular Biology
- Abstract
- Pathogenic bacteria such as Streptococcus pyogenes have evolved different mechanisms to evade host immune defenses, primarily through the expression of virulence factors. Among these, the Streptococcal nuclease A (SpnA), a cell wall-associated protein, is important in bacterial pathogenesis. SpnA hydrolyzes host DNA present within neutrophil extracellular traps (NETs), therefore helping bacteria to evade the innate immunity. In addition, SpnA interacts with other bacterial proteins such as IdeS, an enzyme that degrades IgG proteins, which further represses the host immune response. However, the interaction of SpnA with host cell proteins remains to be understood. Recent unpublished studies show a possible interaction of SpnA with... (More)
- Pathogenic bacteria such as Streptococcus pyogenes have evolved different mechanisms to evade host immune defenses, primarily through the expression of virulence factors. Among these, the Streptococcal nuclease A (SpnA), a cell wall-associated protein, is important in bacterial pathogenesis. SpnA hydrolyzes host DNA present within neutrophil extracellular traps (NETs), therefore helping bacteria to evade the innate immunity. In addition, SpnA interacts with other bacterial proteins such as IdeS, an enzyme that degrades IgG proteins, which further represses the host immune response. However, the interaction of SpnA with host cell proteins remains to be understood. Recent unpublished studies show a possible interaction of SpnA with β2-microglobulin (β2M), which could be involved in immune evasion and bacterial survival. The aim of this study is to understand the role of SpnA in the pathogenesis of S. pyogenes, in particular its possible interaction with host cell proteins, such as β2M. This has been achieved using a combination of affinity-pulldown assays together with quantitative proteomics mass spectrometry, covalent protein cross-linking, and infection assay. Here, we validated the possible interaction between SpnA and β2M. Furthermore, we demonstrated that SpnA is able to interact with a variety of other host proteins, suggesting a broader role in modulating the host immune response. We also observed some evidence of S. pyogenes survival inside the host cells, which may be related to SpnA-induced host proteome reorganization and immune evasion. In addition, our results also point to a possible role of SpnA in activation of the NF-κB signaling pathway in monocytes. In summary, this study extends our knowledge of the possible roles of SpnA during S. pyogenes infection. Our results indicate that in addition to its known role in suppressing the host immune response by degrading NETs, SpnA also binds several host cell proteins to promote bacterial survival and modulate cell signaling. (Less)
- Popular Abstract
- SpnA: The secret weapon Streptococcus pyogenes uses to evade the immune system
Streptococcus pyogenes (group A streptococcus or GAS) is a common but dangerous bacterium that causes a wide range of illnesses, from mild sore throats to potentially lethal infections such as flesh-eating disease and sepsis. It is responsible for over half a million deaths worldwide each year. Despite its impact, there is still no vaccine, and the rise of antibiotic resistance makes finding new treatments more urgent than ever. SpnA (Streptococcal nuclease A) is one of the bacterium’s proteins whose functions are still not fully understood. Scientists used to think that SpnA’s main role was to help the bacteria escape our immune system by breaking down... (More) - SpnA: The secret weapon Streptococcus pyogenes uses to evade the immune system
Streptococcus pyogenes (group A streptococcus or GAS) is a common but dangerous bacterium that causes a wide range of illnesses, from mild sore throats to potentially lethal infections such as flesh-eating disease and sepsis. It is responsible for over half a million deaths worldwide each year. Despite its impact, there is still no vaccine, and the rise of antibiotic resistance makes finding new treatments more urgent than ever. SpnA (Streptococcal nuclease A) is one of the bacterium’s proteins whose functions are still not fully understood. Scientists used to think that SpnA’s main role was to help the bacteria escape our immune system by breaking down special DNA webs, called neutrophil extracellular traps (NETs), that our immune cells use to catch and kill bacteria. NETs are sticky networks of DNA and proteins released by immune cells to trap invaders. However, new research shows that SpnA does even more: it seems to bind to a human protein called β2-microglobulin, which is involved in immune system signaling. Using advanced mass spectrometry, a technique that identifies and measures proteins by weighing their tiny fragments, we mapped SpnA’s interactions with host cell proteins and we found out that SpnA interacts with many different host cell proteins. We also discovered that S. pyogenes can invade and survive within our cells for hours, actively producing new proteins to keep the infection going. Moreover, SpnA can stimulate immune cells and trigger important signaling pathways. This indicates that this protein is much more important to the overall infection process than we initially thought. This study not only expands our understanding of how this mysterious bacterium hijacks our immune system, but also highlights new targets for treatments or vaccines, offering hope against this resilient and deadly pathogen. (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/9214706
- author
- Panella, Silvia
- supervisor
- organization
- course
- MOBN03 20242
- year
- 2025
- type
- H2 - Master's Degree (Two Years)
- subject
- language
- English
- id
- 9214706
- date added to LUP
- 2025-10-31 15:50:19
- date last changed
- 2025-10-31 15:50:19
@misc{9214706,
abstract = {{Pathogenic bacteria such as Streptococcus pyogenes have evolved different mechanisms to evade host immune defenses, primarily through the expression of virulence factors. Among these, the Streptococcal nuclease A (SpnA), a cell wall-associated protein, is important in bacterial pathogenesis. SpnA hydrolyzes host DNA present within neutrophil extracellular traps (NETs), therefore helping bacteria to evade the innate immunity. In addition, SpnA interacts with other bacterial proteins such as IdeS, an enzyme that degrades IgG proteins, which further represses the host immune response. However, the interaction of SpnA with host cell proteins remains to be understood. Recent unpublished studies show a possible interaction of SpnA with β2-microglobulin (β2M), which could be involved in immune evasion and bacterial survival. The aim of this study is to understand the role of SpnA in the pathogenesis of S. pyogenes, in particular its possible interaction with host cell proteins, such as β2M. This has been achieved using a combination of affinity-pulldown assays together with quantitative proteomics mass spectrometry, covalent protein cross-linking, and infection assay. Here, we validated the possible interaction between SpnA and β2M. Furthermore, we demonstrated that SpnA is able to interact with a variety of other host proteins, suggesting a broader role in modulating the host immune response. We also observed some evidence of S. pyogenes survival inside the host cells, which may be related to SpnA-induced host proteome reorganization and immune evasion. In addition, our results also point to a possible role of SpnA in activation of the NF-κB signaling pathway in monocytes. In summary, this study extends our knowledge of the possible roles of SpnA during S. pyogenes infection. Our results indicate that in addition to its known role in suppressing the host immune response by degrading NETs, SpnA also binds several host cell proteins to promote bacterial survival and modulate cell signaling.}},
author = {{Panella, Silvia}},
language = {{eng}},
note = {{Student Paper}},
title = {{The role of streptococcal nuclease SpnA in host interactions and response}},
year = {{2025}},
}