Publicação
Copine 1 and its partners involved in repair of Pneumolysin-induced plasma membrane damage
| dc.contributor.advisor | Costa, Sílvia Vale | |
| dc.contributor.advisor | Sousa, Sandra | |
| dc.contributor.advisor | Ferraz, Ricardo | |
| dc.contributor.author | Monteiro, João Pedro Moreira Alves | |
| dc.date.accessioned | 2026-02-25T10:24:14Z | |
| dc.date.available | 2026-02-25T10:24:14Z | |
| dc.date.issued | 2025-11-20 | |
| dc.description.abstract | Streptococcus pneunoniae is a major global health threat, causing diseases such as otitis media, pneumonia and meningites. The World Health Organization estimates that S. pneumoniae infections kill abou tone million children annually. The emergence of antibiotic-resistant serotypes has exacerbated disease burden, complicating treatment and placing additional burden on public health systems. Therefore, new therapeutic strategies to fight pneumococcal infections are urgently needed, which hinges on a detailed knowledge of the host-bacteria interaction mechanisms. One of the ways through which S. pneumoniae interacts with the host cell is via secretion of pneumolysin (PLY). PLY is a pore-formingtoxin that disrupts host cell plasma membrane (PM) and leads to cell lysis, tissue injury and dysregulation of imune responses that consequently allow bacterial spread. Host cells have evolved repair mechanisms to counteract PLY-induced PM damage, including PM blebbing and vesicular shedding. Our group previously showed that vesicles shed by PLY-intoxicated cells were enriched in Copine 1 and 3 (CPNE1 and CPNE3). We also demonstrated that CPNE1 and CPNE3 depletion increased cell susceptibility to PLY damage, suggesting their involement in PM repair. However, the mechanism by which they promote PM repair is unknown. To shed light into this mechanism, we investigated the localization and interacting partners of CPNE1 and CPNE3 during PLY intoxication and S. pneumoniae infection, using confocal microscopy and proteomics. We observed that infection and PLY intoxication triggered CPNE1 and CPNE3 recruitment to the PM and their co-localization with cortical accumulations of non-muscle myosin IIA and Gp96, which are hallmarkers of PM damage. Under homeostasis, CPNE1 associated with proteins involved in PM maintenance and vesicular traffcking, whereas during PLY intoxxication, CPNE1’s proximity network shifted to include stress-response proteins, cytoskeletal proteins and known repair machinery. These data reflected a change in CPNE1’s functions, suggesting that CPNE1 might be involved in cytoskeleton regulation and vesicular traffcking during PM repair. Overall, our findings contribute to a better understanding of the molecular mechanisms underlying PM repair triggered by PLY-induced damage. By elucidating the role of CPNE1 and its interaction network in PM repair, this research highlights potential therapeutic targets to enhance host cell resilience against bacterial infections that compromisse PM integrity. | eng |
| dc.identifier.tid | 204179580 | |
| dc.identifier.uri | http://hdl.handle.net/10400.22/31900 | |
| dc.language.iso | eng | |
| dc.rights.uri | N/A | |
| dc.subject | Bacterial infection | |
| dc.subject | Pneumolysin | |
| dc.subject | Plasma membrane repair | |
| dc.subject | Streptococcus pneumoniae | |
| dc.subject | Therapeutic targets | |
| dc.title | Copine 1 and its partners involved in repair of Pneumolysin-induced plasma membrane damage | por |
| dc.type | master thesis | |
| dspace.entity.type | Publication | |
| thesis.degree.name | Master’s in Biochemistry in Health – Biotechnology |