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Published on: May 13, 2020
Functional study of Bergeyella cardium KP-43 subfamily peptidases as putative T9SS cargo
Tian Li1, Yiwen Gao1, Xiaoyue Zhang1
1Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, China.
Insights
Bergeyella cardium peptidases SpBcA and SpBcB are active virulence factors. SpBcA self-activates and degrades host molecules, contributing to bacterial infection mechanisms.
Area of Science:
- Microbiology
- Bacterial Pathogenesis
- Enzymology
Background:
- Bergeyella cardium infections pose a threat to human health.
- The specific virulence mechanisms of B. cardium remain largely unknown.
- Peptidases are recognized as crucial virulence factors in many bacterial pathogens.
Purpose of the Study:
- To identify and characterize peptidases from B. cardium.
- To elucidate the role of these peptidases as potential virulence factors.
- To investigate the auto-activation mechanism of identified peptidases.
Main Methods:
- Identification of KP-43 subfamily peptidases (SpBcA, SpBcB, SpBcC) in B. cardium.
- In vitro protease activity assays.
- Analysis of peptidase auto-activation and substrate degradation.
- In vivo cell death assays.
Main Results:
- SpBcA and SpBcB exhibit in vitro protease activity and possess inhibitory propeptides.
- SpBcA undergoes auto-cleavage for activation, releasing its inhibitory propeptide.
- SpBcA degrades host defense proteins like fibrinogen and LL-37, and induces cell death in vivo.
Conclusions:
- SpBcA functions as a key virulence factor in B. cardium infections.
- The auto-cleavage mechanism of SpBcA is a novel regulatory pathway.
- This research provides insights into B. cardium virulence strategies involving peptidases.
Abstract:
Bergeyella cardium causes infections in human organs. However, the mechanism of the virulence of B. cardium is unclear. Peptidases are important virulence factors in bacterial pathogens. Here, we identified three KP-43 subfamily peptidases, SpBcA, SpBcB and SpBcC, which are putative T9SS cargo proteins, and analyzed their protease activity. SpBcA and SpBcB are active in vitro and contain a propeptide that passes through the active site of the S8 peptidase domain and inhibits its activity. SpBcA activates itself by cleaving the propeptide at N102 within the TSNA (100-103) peptide and a putative cleavage site at 116-120 (TSPGL). Additionally, SpBcA degrades host defense molecules, fibrinogen, antimicrobial peptide LL-37 and gelatin in vitro and induces cell death in vivo, suggesting its role as a virulence factor. This study revealed the self-cleavage regulatory mechanism of SpBcA and provided a basis for studying how B. cardium uses peptidases as virulence factors in vivo.
