Host-Cell-Dependent Roles of E-Cadherin in <i>Serratia</i> Invasion
Bacteria use cell surface proteins to mediate host–pathogen interactions. Proteins responsible for cell adhesion, including E-cadherin, serve as receptors for entry into the host cell. We have previously shown that an increase in eukaryotic cell sensitivity to <i>Serratia grimesii</i> co...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/23/17075 |
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| author | Olga Tsaplina Ekaterina Lomert Yuliya Berson |
| author_facet | Olga Tsaplina Ekaterina Lomert Yuliya Berson |
| author_sort | Olga Tsaplina |
| collection | DOAJ |
| description | Bacteria use cell surface proteins to mediate host–pathogen interactions. Proteins responsible for cell adhesion, including E-cadherin, serve as receptors for entry into the host cell. We have previously shown that an increase in eukaryotic cell sensitivity to <i>Serratia grimesii</i> correlates with an increase in E-cadherin expression. On the other hand, <i>Serratia proteamaculans</i> invasion involves the EGFR, which can interact with E-cadherin on the surface of host cells. Therefore, we investigated the role of E-cadherin in <i>Serratia</i> invasion into M-HeLa and Caco-2 cells. Bacterial infection increased E-cadherin expression in both cell lines. Moreover, E-cadherin was detected in the Caco-2 cells in a full-length form and in the M-HeLa cells in only a truncated form in response to incubation with bacteria. Transfection with siRNA targeting E-cadherin inhibited <i>S. proteamaculans</i> invasion only into the Caco-2 cells. Thus, only full-length E-cadherin is involved in <i>S. proteamaculans</i> invasion. On the other hand, transfection with siRNA targeting E-cadherin inhibited <i>S. grimesii</i> invasion into both cell lines. Thus, not only may full-length E-cadherin but also truncated E-cadherin be involved in <i>S. grimesii</i> invasion. Truncated E-cadherin can be formed as a result of cleavage by bacterial proteases or the Ca<sup>2+</sup>-activated cellular protease ADAM10. The rate of Ca<sup>2+</sup> accumulation in the host cells depends on the number of bacteria per cell upon infection. During incubation, Ca<sup>2+</sup> accumulates only when more than 500 <i>S. grimesii</i> bacteria are infected per eukaryotic cell, and only under these conditions does the ADAM10 inhibitor reduce the sensitivity of the cells to bacteria. An EGFR inhibitor has the same quantitative effect on <i>S. grimesii</i> invasion. Apparently, as a result of infection with <i>S. grimesii</i>, Ca<sup>2+</sup> accumulates in the host cells and may activate the ADAM10 sheddase, which can promote invasion by cleaving E-cadherin and, as a result, triggering EGFR signaling. Thus, the invasion of <i>S. proteamaculans</i> can only be promoted by full-length E-cadherin, and <i>S. grimesii</i> invasion can be promoted by both full-length and truncated E-cadherin. |
| first_indexed | 2024-03-09T01:49:06Z |
| format | Article |
| id | doaj.art-9ee341c7b80e412a8316f366464796ea |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T01:49:06Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-9ee341c7b80e412a8316f366464796ea2023-12-08T15:18:17ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-12-0124231707510.3390/ijms242317075Host-Cell-Dependent Roles of E-Cadherin in <i>Serratia</i> InvasionOlga Tsaplina0Ekaterina Lomert1Yuliya Berson2Institute of Cytology, Russian Academy of Sciences, Tikhoretsky av. 4, 194064 St Petersburg, RussiaInstitute of Cytology, Russian Academy of Sciences, Tikhoretsky av. 4, 194064 St Petersburg, RussiaInstitute of Cytology, Russian Academy of Sciences, Tikhoretsky av. 4, 194064 St Petersburg, RussiaBacteria use cell surface proteins to mediate host–pathogen interactions. Proteins responsible for cell adhesion, including E-cadherin, serve as receptors for entry into the host cell. We have previously shown that an increase in eukaryotic cell sensitivity to <i>Serratia grimesii</i> correlates with an increase in E-cadherin expression. On the other hand, <i>Serratia proteamaculans</i> invasion involves the EGFR, which can interact with E-cadherin on the surface of host cells. Therefore, we investigated the role of E-cadherin in <i>Serratia</i> invasion into M-HeLa and Caco-2 cells. Bacterial infection increased E-cadherin expression in both cell lines. Moreover, E-cadherin was detected in the Caco-2 cells in a full-length form and in the M-HeLa cells in only a truncated form in response to incubation with bacteria. Transfection with siRNA targeting E-cadherin inhibited <i>S. proteamaculans</i> invasion only into the Caco-2 cells. Thus, only full-length E-cadherin is involved in <i>S. proteamaculans</i> invasion. On the other hand, transfection with siRNA targeting E-cadherin inhibited <i>S. grimesii</i> invasion into both cell lines. Thus, not only may full-length E-cadherin but also truncated E-cadherin be involved in <i>S. grimesii</i> invasion. Truncated E-cadherin can be formed as a result of cleavage by bacterial proteases or the Ca<sup>2+</sup>-activated cellular protease ADAM10. The rate of Ca<sup>2+</sup> accumulation in the host cells depends on the number of bacteria per cell upon infection. During incubation, Ca<sup>2+</sup> accumulates only when more than 500 <i>S. grimesii</i> bacteria are infected per eukaryotic cell, and only under these conditions does the ADAM10 inhibitor reduce the sensitivity of the cells to bacteria. An EGFR inhibitor has the same quantitative effect on <i>S. grimesii</i> invasion. Apparently, as a result of infection with <i>S. grimesii</i>, Ca<sup>2+</sup> accumulates in the host cells and may activate the ADAM10 sheddase, which can promote invasion by cleaving E-cadherin and, as a result, triggering EGFR signaling. Thus, the invasion of <i>S. proteamaculans</i> can only be promoted by full-length E-cadherin, and <i>S. grimesii</i> invasion can be promoted by both full-length and truncated E-cadherin.https://www.mdpi.com/1422-0067/24/23/17075bacterial invasionE-cadherinADAM10hemolysin ShlA |
| spellingShingle | Olga Tsaplina Ekaterina Lomert Yuliya Berson Host-Cell-Dependent Roles of E-Cadherin in <i>Serratia</i> Invasion International Journal of Molecular Sciences bacterial invasion E-cadherin ADAM10 hemolysin ShlA |
| title | Host-Cell-Dependent Roles of E-Cadherin in <i>Serratia</i> Invasion |
| title_full | Host-Cell-Dependent Roles of E-Cadherin in <i>Serratia</i> Invasion |
| title_fullStr | Host-Cell-Dependent Roles of E-Cadherin in <i>Serratia</i> Invasion |
| title_full_unstemmed | Host-Cell-Dependent Roles of E-Cadherin in <i>Serratia</i> Invasion |
| title_short | Host-Cell-Dependent Roles of E-Cadherin in <i>Serratia</i> Invasion |
| title_sort | host cell dependent roles of e cadherin in i serratia i invasion |
| topic | bacterial invasion E-cadherin ADAM10 hemolysin ShlA |
| url | https://www.mdpi.com/1422-0067/24/23/17075 |
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