Binding of Kingella kingae RtxA Toxin Depends on Cell Surface Oligosaccharides, but Not on beta(2) Integrins

0536763 - MBÚ 2021 RIV CH eng J - Článek v odborném periodiku
Rahman, Waheed Ur - Osičková, Adriana - Klímová, Nela - Lora, J. - Balashova, N. - Osička, Radim
Binding of Kingella kingae RtxA Toxin Depends on Cell Surface Oligosaccharides, but Not on beta(2) Integrins.
International Journal of Molecular Sciences. Roč. 21, č. 23 (2020), č. článku 9092. E-ISSN 1422-0067
Grant CEP: GA ČR(CZ) GA18-18079S; GA MŠMT(CZ) LM2018133
Institucionální podpora: RVO:61388971
Klíčová slova: integrins * Kingella kingae * oligosaccharides
Obor OECD: Microbiology
Impakt faktor: 5.924, rok: 2020
Způsob publikování: Open access
https://www.mdpi.com/1422-0067/21/23/9092

The Gram-negative coccobacillus Kingella kingae is increasingly recognized as an important invasive pediatric pathogen that causes mostly bacteremia and skeletal system infections. K. kingae secretes an RtxA toxin that belongs to a broad family of the RTX (Repeats in ToXin) cytotoxins produced by bacterial pathogens. Recently, we demonstrated that membrane cholesterol facilitates interaction of RtxA with target cells, but other cell surface structures potentially involved in toxin binding to cells remain unknown. We show that deglycosylation of cell surface structures by glycosidase treatment, or inhibition of protein N- and O-glycosylation by chemical inhibitors substantially reduces RtxA binding to target cells. Consequently, the deglycosylated cells were more resistant to cytotoxic activity of RtxA. Moreover, experiments on cells expressing or lacking cell surface integrins of the beta(2) family revealed that, unlike some other cytotoxins of the RTX family, K. kingae RtxA does not bind target cells via the beta(2) integrins. Our results, hence, show that RtxA binds cell surface oligosaccharides present on all mammalian cells but not the leukocyte-restricted beta(2) integrins. This explains the previously observed interaction of the toxin with a broad range of cell types of various mammalian species and reveals that RtxA belongs to the group of broadly cytolytic RTX hemolysins.
Trvalý link: http://hdl.handle.net/11104/0314511