Regulation of integrin α5β1-mediated Staphylococcus aureus cellular invasion by the septin cytoskeleton
Staphylococcus aureus, a Gram-positive bacterial pathogen, is an urgent health threat causing a wide range of clinical infections. Originally viewed as a strict extracellular pathogen, accumulating evidence has revealed S. aureus to be a facultative intracellular pathogen subverting host cell signal...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | European Journal of Cell Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0171933523000742 |
| _version_ | 1827687061516189696 |
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| author | Stevens Robertin Dominik Brokatzky Damián Lobato-Márquez Serge Mostowy |
| author_facet | Stevens Robertin Dominik Brokatzky Damián Lobato-Márquez Serge Mostowy |
| author_sort | Stevens Robertin |
| collection | DOAJ |
| description | Staphylococcus aureus, a Gram-positive bacterial pathogen, is an urgent health threat causing a wide range of clinical infections. Originally viewed as a strict extracellular pathogen, accumulating evidence has revealed S. aureus to be a facultative intracellular pathogen subverting host cell signalling to support invasion. The majority of clinical isolates produce fibronectin-binding proteins A and B (FnBPA and FnBPB) to interact with host integrin α5β1, a key component of focal adhesions. S. aureus binding of integrin α5β1 promotes its clustering on the host cell surface, triggering activation of focal adhesion kinase (FAK) and cytoskeleton rearrangements to promote bacterial invasion into non-phagocytic cells. Here, we discover that septins, a component of the cytoskeleton that assembles on membranes, are recruited as collar-like structures with actin to S. aureus invasion sites engaging integrin α5β1. To investigate septin recruitment to the plasma membrane in a bacteria-free system, we used FnBPA-coated latex beads and showed that septins are recruited upon activation of integrin α5β1. SEPT2 depletion reduced S. aureus invasion, but increased surface expression of integrin α5 and adhesion of S. aureus to host cells. Consistent with this, SEPT2 depletion increased cellular protein levels of integrin α5 and β1 subunits, as well as FAK. Collectively, these results provide insights into regulation of integrin α5β1 and invasion of S. aureus by the septin cytoskeleton. |
| first_indexed | 2024-03-10T09:27:21Z |
| format | Article |
| id | doaj.art-2a4e19b813af4c758b710d43022eaf83 |
| institution | Directory Open Access Journal |
| issn | 0171-9335 |
| language | English |
| last_indexed | 2024-03-10T09:27:21Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | European Journal of Cell Biology |
| spelling | doaj.art-2a4e19b813af4c758b710d43022eaf832023-11-22T04:46:11ZengElsevierEuropean Journal of Cell Biology0171-93352023-12-011024151359Regulation of integrin α5β1-mediated Staphylococcus aureus cellular invasion by the septin cytoskeletonStevens Robertin0Dominik Brokatzky1Damián Lobato-Márquez2Serge Mostowy3Department of Infection Biology, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United KingdomDepartment of Infection Biology, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United KingdomDepartment of Infection Biology, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United KingdomCorresponding author.; Department of Infection Biology, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United KingdomStaphylococcus aureus, a Gram-positive bacterial pathogen, is an urgent health threat causing a wide range of clinical infections. Originally viewed as a strict extracellular pathogen, accumulating evidence has revealed S. aureus to be a facultative intracellular pathogen subverting host cell signalling to support invasion. The majority of clinical isolates produce fibronectin-binding proteins A and B (FnBPA and FnBPB) to interact with host integrin α5β1, a key component of focal adhesions. S. aureus binding of integrin α5β1 promotes its clustering on the host cell surface, triggering activation of focal adhesion kinase (FAK) and cytoskeleton rearrangements to promote bacterial invasion into non-phagocytic cells. Here, we discover that septins, a component of the cytoskeleton that assembles on membranes, are recruited as collar-like structures with actin to S. aureus invasion sites engaging integrin α5β1. To investigate septin recruitment to the plasma membrane in a bacteria-free system, we used FnBPA-coated latex beads and showed that septins are recruited upon activation of integrin α5β1. SEPT2 depletion reduced S. aureus invasion, but increased surface expression of integrin α5 and adhesion of S. aureus to host cells. Consistent with this, SEPT2 depletion increased cellular protein levels of integrin α5 and β1 subunits, as well as FAK. Collectively, these results provide insights into regulation of integrin α5β1 and invasion of S. aureus by the septin cytoskeleton.http://www.sciencedirect.com/science/article/pii/S0171933523000742CytoskeletonIntegrinSeptinsStaphylococcus aureus |
| spellingShingle | Stevens Robertin Dominik Brokatzky Damián Lobato-Márquez Serge Mostowy Regulation of integrin α5β1-mediated Staphylococcus aureus cellular invasion by the septin cytoskeleton European Journal of Cell Biology Cytoskeleton Integrin Septins Staphylococcus aureus |
| title | Regulation of integrin α5β1-mediated Staphylococcus aureus cellular invasion by the septin cytoskeleton |
| title_full | Regulation of integrin α5β1-mediated Staphylococcus aureus cellular invasion by the septin cytoskeleton |
| title_fullStr | Regulation of integrin α5β1-mediated Staphylococcus aureus cellular invasion by the septin cytoskeleton |
| title_full_unstemmed | Regulation of integrin α5β1-mediated Staphylococcus aureus cellular invasion by the septin cytoskeleton |
| title_short | Regulation of integrin α5β1-mediated Staphylococcus aureus cellular invasion by the septin cytoskeleton |
| title_sort | regulation of integrin α5β1 mediated staphylococcus aureus cellular invasion by the septin cytoskeleton |
| topic | Cytoskeleton Integrin Septins Staphylococcus aureus |
| url | http://www.sciencedirect.com/science/article/pii/S0171933523000742 |
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