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Published on: January 7, 2022
Pathogenic Streptococcus strains employ novel escape strategy to inhibit bacteriostatic effect mediated by mammalian
Jing Wang1, Youjun Feng2, Changjun Wang3
1Translational Medicine Center, PLA Hospital No.454, Nanjing, China.
Abstract:
Pathogenic streptococcal species are responsible for some of the most lethal and prevalent animal and human infections. Previous reports have identified a candidate pathogenicity island (PAI) in two highly virulent clinical isolates of Streptococcus suis type 2, a causative agent of high-mortality streptococcal toxic shock syndrome. This PAI contains a type-IVC secretion system C subgroup (type-IVC secretion system) that is involved in the secretion of unknown pathogenic effectors that are responsible for streptococcal toxic shock syndrome caused by highly virulent strains of S. suis. Both virulence protein B4 and virulence protein D4 were demonstrated to be key components of this type-IVC secretion system. In this study, we identify a new PAI family across 3 streptococcal species; Streptococcus genomic island contains type-IV secretion system, which contains a genomic island type-IVC secretion system and a novel PPIase molecule, SP1. SP1 is shown to interact with a component of innate immunity, peptidoglycan recognition protein (PGLYRP-1) and to perturb the PGLYRP-1-mediated bacteriostatic effect by interacting with protein PGLYRP-1. Our study elucidates a novel mechanism by which bacteria escape by components of the innate immune system by secretion of the SP1 protein in pathogenic Streptococci, which then interacts with PGLYRP-1 from the host. Our results provide potential targets for the development of new antimicrobial drugs against bacteria with resistance to innate host immunity.
Insights
Pathogenic Streptococci use a novel SP1 protein secreted via a type-IVC secretion system to evade host innate immunity. This interaction with peptidoglycan recognition protein-1 (PGLYRP-1) offers new antimicrobial drug targets.
Area of Science:
- Microbiology
- Immunology
- Molecular Biology
Background:
- Pathogenic streptococci cause severe infections in animals and humans.
- A pathogenicity island (PAI) with a type-IVC secretion system is linked to virulent Streptococcus suis infections.
- This system secretes effectors causing streptococcal toxic shock syndrome.
Purpose of the Study:
- To identify new PAI families in streptococcal species.
- To investigate the function of a novel PPIase molecule, SP1, within a PAI.
- To understand how pathogenic Streptococci evade innate immunity.
Main Methods:
- Genomic analysis to identify new PAI families.
- Biochemical assays to study protein interactions.
- Functional assays to assess immune evasion mechanisms.
Main Results:
- A new PAI family containing a type-IVC secretion system and SP1 was identified across three streptococcal species.
- SP1 directly interacts with peptidoglycan recognition protein-1 (PGLYRP-1).
- SP1 disrupts the PGLYRP-1-mediated bacteriostatic effect, enabling bacterial immune evasion.
Conclusions:
- Pathogenic Streptococci utilize the secreted SP1 protein to antagonize PGLYRP-1, a key innate immune component.
- This mechanism represents a novel bacterial strategy for escaping host immune defenses.
- The SP1-PGLYRP-1 interaction presents a potential target for developing novel antimicrobial therapies against resistant bacteria.
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