Functional study of Bergeyella cardium KP-43 subfamily peptidases as putative T9SS cargo

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 ca...

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Main Authors: Tian Li, Yiwen Gao, Xiaoyue Zhang, Yuxiao Zhao, Fuyao Hu, Wei Li, Lixiang Li, Hongwei Pan, Yi Zhang, Ying Chen
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Communications Biology
Online Access:https://doi.org/10.1038/s42003-025-07996-y
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author Tian Li
Yiwen Gao
Xiaoyue Zhang
Yuxiao Zhao
Fuyao Hu
Wei Li
Lixiang Li
Hongwei Pan
Yi Zhang
Ying Chen
author_facet Tian Li
Yiwen Gao
Xiaoyue Zhang
Yuxiao Zhao
Fuyao Hu
Wei Li
Lixiang Li
Hongwei Pan
Yi Zhang
Ying Chen
author_sort Tian Li
collection DOAJ
description 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.
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spelling doaj-art-e698eb1e413445f894001eb0f8c976552025-08-20T02:17:02ZengNature PortfolioCommunications Biology2399-36422025-04-018111610.1038/s42003-025-07996-yFunctional study of Bergeyella cardium KP-43 subfamily peptidases as putative T9SS cargoTian Li0Yiwen Gao1Xiaoyue Zhang2Yuxiao Zhao3Fuyao Hu4Wei Li5Lixiang Li6Hongwei Pan7Yi Zhang8Ying Chen9Department of Clinical Laboratory, Qilu Hospital of Shandong UniversityDepartment of Clinical Laboratory, Qilu Hospital of Shandong UniversityDepartment of Clinical Laboratory, Qilu Hospital of Shandong UniversityDepartment of Clinical Laboratory, Qilu Hospital of Shandong UniversityDepartment of Clinical Laboratory, Qilu Hospital of Shandong UniversityDepartment of Clinical Laboratory, Qilu Hospital of Shandong UniversityDepartment of Gastroenterology, Qilu Hospital of Shandong UniversityDepartment of Clinical Laboratory, Qilu Hospital of Shandong UniversityDepartment of Clinical Laboratory, Qilu Hospital of Shandong UniversityDepartment of Clinical Laboratory, Qilu Hospital of Shandong UniversityAbstract 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.https://doi.org/10.1038/s42003-025-07996-y
spellingShingle Tian Li
Yiwen Gao
Xiaoyue Zhang
Yuxiao Zhao
Fuyao Hu
Wei Li
Lixiang Li
Hongwei Pan
Yi Zhang
Ying Chen
Functional study of Bergeyella cardium KP-43 subfamily peptidases as putative T9SS cargo
Communications Biology
title Functional study of Bergeyella cardium KP-43 subfamily peptidases as putative T9SS cargo
title_full Functional study of Bergeyella cardium KP-43 subfamily peptidases as putative T9SS cargo
title_fullStr Functional study of Bergeyella cardium KP-43 subfamily peptidases as putative T9SS cargo
title_full_unstemmed Functional study of Bergeyella cardium KP-43 subfamily peptidases as putative T9SS cargo
title_short Functional study of Bergeyella cardium KP-43 subfamily peptidases as putative T9SS cargo
title_sort functional study of bergeyella cardium kp 43 subfamily peptidases as putative t9ss cargo
url https://doi.org/10.1038/s42003-025-07996-y
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