Binding of <i>Kingella kingae</i> RtxA Toxin Depends on Cell Surface Oligosaccharides, but Not on β<sub>2</sub> Integrins
The Gram-negative coccobacillus <i>Kingella kingae</i> is increasingly recognized as an important invasive pediatric pathogen that causes mostly bacteremia and skeletal system infections. <i>K. kingae</i> secretes an RtxA toxin that belongs to a broad family of the RTX (Repea...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-11-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/21/23/9092 |
| Summary: | The Gram-negative coccobacillus <i>Kingella kingae</i> is increasingly recognized as an important invasive pediatric pathogen that causes mostly bacteremia and skeletal system infections. <i>K. kingae</i> 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 β<sub>2</sub> family revealed that, unlike some other cytotoxins of the RTX family, <i>K. kingae</i> RtxA does not bind target cells via the β<sub>2</sub> integrins. Our results, hence, show that RtxA binds cell surface oligosaccharides present on all mammalian cells but not the leukocyte-restricted β<sub>2</sub> 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. |
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| ISSN: | 1661-6596 1422-0067 |