Kingella kingae cytotoxin RtxA induces an innate immune response in oral epithelial cells

The genus Kingella comprises four common species: the commensals K. oralis and K. denitrificans, the emerging paediatric pathogen K. kingae and the novel species K. negevensis. Improved diagnostic methods have led to the recognition of K. kingae as a major cause of septic arthritis in young children...

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Main Authors: Eliska Ruzickova, Karyna Zhuk, Kevin Munoz Navarrete, Adriana Osickova, Radim Osicka
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Current Research in Microbial Sciences
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Online Access:http://www.sciencedirect.com/science/article/pii/S2666517425000550
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author Eliska Ruzickova
Karyna Zhuk
Kevin Munoz Navarrete
Adriana Osickova
Radim Osicka
author_facet Eliska Ruzickova
Karyna Zhuk
Kevin Munoz Navarrete
Adriana Osickova
Radim Osicka
author_sort Eliska Ruzickova
collection DOAJ
description The genus Kingella comprises four common species: the commensals K. oralis and K. denitrificans, the emerging paediatric pathogen K. kingae and the novel species K. negevensis. Improved diagnostic methods have led to the recognition of K. kingae as a major cause of septic arthritis in young children. The key virulence factor responsible for the pathogenesis of K. kingae is its cytotoxin RtxA, which is thought to facilitate host invasion. After binding to target cells, RtxA inserts into the host cell membrane and forms ion-conducting membrane pores that disrupt normal cell physiology and ultimately lead to cell death. In this study, we analysed the pro-inflammatory response of oral epithelial cells to a clinical isolate of K. kingae, its isogenic RtxA-deficient mutant and the commensals K. oralis and K. denitrificans, which do not produce RtxA. The results show that infection of cells with K. kingae, but not with the RtxA-deficient mutant and the commensal species, leads to increased expression and secretion of certain pro-inflammatory cytokines and chemokines. Furthermore, the RtxA-producing K. kingae, but not the RtxA-deficient mutant, upregulated the expression of DEFB4A and SLPI genes encoding antimicrobial peptides. These findings demonstrate that the RtxA toxin induces an innate immune response in oral epithelial cells.
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spelling doaj-art-2eb069caafb644f6a70c770e5efe06a62025-08-20T03:11:26ZengElsevierCurrent Research in Microbial Sciences2666-51742025-01-01810039310.1016/j.crmicr.2025.100393Kingella kingae cytotoxin RtxA induces an innate immune response in oral epithelial cellsEliska Ruzickova0Karyna Zhuk1Kevin Munoz Navarrete2Adriana Osickova3Radim Osicka4Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech Republic; Faculty of Science, Charles University, Prague, Czech RepublicInstitute of Microbiology of the Czech Academy of Sciences, Prague, Czech Republic; Faculty of Science, Charles University, Prague, Czech RepublicInstitute of Microbiology of the Czech Academy of Sciences, Prague, Czech RepublicInstitute of Microbiology of the Czech Academy of Sciences, Prague, Czech RepublicInstitute of Microbiology of the Czech Academy of Sciences, Prague, Czech Republic; Corresponding author.The genus Kingella comprises four common species: the commensals K. oralis and K. denitrificans, the emerging paediatric pathogen K. kingae and the novel species K. negevensis. Improved diagnostic methods have led to the recognition of K. kingae as a major cause of septic arthritis in young children. The key virulence factor responsible for the pathogenesis of K. kingae is its cytotoxin RtxA, which is thought to facilitate host invasion. After binding to target cells, RtxA inserts into the host cell membrane and forms ion-conducting membrane pores that disrupt normal cell physiology and ultimately lead to cell death. In this study, we analysed the pro-inflammatory response of oral epithelial cells to a clinical isolate of K. kingae, its isogenic RtxA-deficient mutant and the commensals K. oralis and K. denitrificans, which do not produce RtxA. The results show that infection of cells with K. kingae, but not with the RtxA-deficient mutant and the commensal species, leads to increased expression and secretion of certain pro-inflammatory cytokines and chemokines. Furthermore, the RtxA-producing K. kingae, but not the RtxA-deficient mutant, upregulated the expression of DEFB4A and SLPI genes encoding antimicrobial peptides. These findings demonstrate that the RtxA toxin induces an innate immune response in oral epithelial cells.http://www.sciencedirect.com/science/article/pii/S2666517425000550Innate immunityKingella kingaeOral epithelial cellsRepeats-in-toxinRtxA
spellingShingle Eliska Ruzickova
Karyna Zhuk
Kevin Munoz Navarrete
Adriana Osickova
Radim Osicka
Kingella kingae cytotoxin RtxA induces an innate immune response in oral epithelial cells
Current Research in Microbial Sciences
Innate immunity
Kingella kingae
Oral epithelial cells
Repeats-in-toxin
RtxA
title Kingella kingae cytotoxin RtxA induces an innate immune response in oral epithelial cells
title_full Kingella kingae cytotoxin RtxA induces an innate immune response in oral epithelial cells
title_fullStr Kingella kingae cytotoxin RtxA induces an innate immune response in oral epithelial cells
title_full_unstemmed Kingella kingae cytotoxin RtxA induces an innate immune response in oral epithelial cells
title_short Kingella kingae cytotoxin RtxA induces an innate immune response in oral epithelial cells
title_sort kingella kingae cytotoxin rtxa induces an innate immune response in oral epithelial cells
topic Innate immunity
Kingella kingae
Oral epithelial cells
Repeats-in-toxin
RtxA
url http://www.sciencedirect.com/science/article/pii/S2666517425000550
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AT karynazhuk kingellakingaecytotoxinrtxainducesaninnateimmuneresponseinoralepithelialcells
AT kevinmunoznavarrete kingellakingaecytotoxinrtxainducesaninnateimmuneresponseinoralepithelialcells
AT adrianaosickova kingellakingaecytotoxinrtxainducesaninnateimmuneresponseinoralepithelialcells
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