Interactome Mapping of Plasminogen-interactive Proteins from Group A Streptococcus by Integrated Mass Spectrometry-based Proteomics
(2023) KIMM01 20231Department of Immunotechnology
Educational programmes, LTH
- Abstract
- Streptococcus pyogenes is a host-adapted human pathogen responsible for causing various infectious diseases, including rheumatic heart disease and acute rheumatic fever, some of which can be fatal to humans. The bacteria contain different pathogenic proteins situated on the cell surface or secreted extracellularly. Many of these proteins have the ability to bind to and activate human plasminogen. Such interaction with plasminogen can lead to irregular fibrinolytic functionality, thereby aiding the infection and spread of S. pyogenes.
However, until nowadays, it’s still unknown whether S.pyogenes M1 serotype contains
special extracellular proteins that can interact with plasminogen and regulate it, and these proteins should be... (More) - Streptococcus pyogenes is a host-adapted human pathogen responsible for causing various infectious diseases, including rheumatic heart disease and acute rheumatic fever, some of which can be fatal to humans. The bacteria contain different pathogenic proteins situated on the cell surface or secreted extracellularly. Many of these proteins have the ability to bind to and activate human plasminogen. Such interaction with plasminogen can lead to irregular fibrinolytic functionality, thereby aiding the infection and spread of S. pyogenes.
However, until nowadays, it’s still unknown whether S.pyogenes M1 serotype contains
special extracellular proteins that can interact with plasminogen and regulate it, and these proteins should be characterized. Proteome mapping was conducted using a high pH fractionation kit to initially reduce the complexity of peptide mixtures, followed by data dependent acquisition (DDA) mass spectrometry. To investigate plasminogen-interactive streptococcal proteins, plasminogen protein and ECH-lysine Sepharose were utilized for the affinity purification experiment, and both data independent acquisition (DIA) and DDA were employed to analyze the pull-down samples. The study resulted in a protein map highlighting the cell wall-associated proteins of S. pyogenes. Within this map, 29 types of proteins were indicated as interactive to human plasminogen. Out of these, six were found to specifically bind to human plasminogen and had not been previously reported. (Less) - Popular Abstract
- Streptococcus pyogenes, or Group A streptococcus (GAS), is a bacterium that causes
many human diseases, from skin infections to severe conditions like rheumatic heart
disease, leading to half a million deaths each year globally. GAS has a unique ability to cling to human skin or throat, where it grows and spreads, effectively dodging the immune system.
One of GAS's crafty tactics involves manipulating human proteins, specifically
plasminogen, which usually helps break down blood clots. Some proteins of GAS can
bind to plasminogen, activating it in a way that helps the bacteria spread within the body.
This clever maneuvering by GAS isn't just a scientific curiosity; it offers a pathway to potential medical breakthroughs. By... (More) - Streptococcus pyogenes, or Group A streptococcus (GAS), is a bacterium that causes
many human diseases, from skin infections to severe conditions like rheumatic heart
disease, leading to half a million deaths each year globally. GAS has a unique ability to cling to human skin or throat, where it grows and spreads, effectively dodging the immune system.
One of GAS's crafty tactics involves manipulating human proteins, specifically
plasminogen, which usually helps break down blood clots. Some proteins of GAS can
bind to plasminogen, activating it in a way that helps the bacteria spread within the body.
This clever maneuvering by GAS isn't just a scientific curiosity; it offers a pathway to potential medical breakthroughs. By understanding how these proteins work, researchers may find new ways to combat the infections caused by GAS. In this project, plasminogen bound material was used to enrich specific proteins that can interact with human plasminogen, samples were measured by mass spectrometry and six specific proteins were characterized. These discoveries provide essential clues for developing new treatments or preventative measures.
In essence, the battle against GAS is complex, but our growing understanding of its
behavior and mechanisms opens exciting avenues for future research and medical
innovations. This knowledge may someday lead to new methods to protect ourselves
from this adaptable and often deadly pathogen. (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/9136733
- author
- Han, Dongnian LU
- supervisor
-
- Johan Malmström LU
- Kathrin Zeller LU
- Di Tang LU
- organization
- course
- KIMM01 20231
- year
- 2023
- type
- H2 - Master's Degree (Two Years)
- subject
- keywords
- Streptococcus pyogenes, secreted proteins, cell wall-associated proteins, data dependent acquisition and data independent acquisition, plasminogen-interactive bacterial proteins, immunotechnology
- language
- English
- additional info
- Master Thesis of Dongnian Han, from Pharmaceutical Technology programme in LTH
- id
- 9136733
- date added to LUP
- 2023-09-07 10:37:42
- date last changed
- 2023-09-07 10:37:42
@misc{9136733,
abstract = {{Streptococcus pyogenes is a host-adapted human pathogen responsible for causing various infectious diseases, including rheumatic heart disease and acute rheumatic fever, some of which can be fatal to humans. The bacteria contain different pathogenic proteins situated on the cell surface or secreted extracellularly. Many of these proteins have the ability to bind to and activate human plasminogen. Such interaction with plasminogen can lead to irregular fibrinolytic functionality, thereby aiding the infection and spread of S. pyogenes.
However, until nowadays, it’s still unknown whether S.pyogenes M1 serotype contains
special extracellular proteins that can interact with plasminogen and regulate it, and these proteins should be characterized. Proteome mapping was conducted using a high pH fractionation kit to initially reduce the complexity of peptide mixtures, followed by data dependent acquisition (DDA) mass spectrometry. To investigate plasminogen-interactive streptococcal proteins, plasminogen protein and ECH-lysine Sepharose were utilized for the affinity purification experiment, and both data independent acquisition (DIA) and DDA were employed to analyze the pull-down samples. The study resulted in a protein map highlighting the cell wall-associated proteins of S. pyogenes. Within this map, 29 types of proteins were indicated as interactive to human plasminogen. Out of these, six were found to specifically bind to human plasminogen and had not been previously reported.}},
author = {{Han, Dongnian}},
language = {{eng}},
note = {{Student Paper}},
title = {{Interactome Mapping of Plasminogen-interactive Proteins from Group A Streptococcus by Integrated Mass Spectrometry-based Proteomics}},
year = {{2023}},
}