دورية أكاديمية
Antimicrobial sensing coupled with cell membrane remodeling mediates antibiotic resistance and virulence in enterococcus faecalis
| العنوان: | Antimicrobial sensing coupled with cell membrane remodeling mediates antibiotic resistance and virulence in enterococcus faecalis |
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| المؤلفون: | Khan, Ayesha, Davlieva, Milya, Panesso, Diana, Rincon, Sandra, Millera, William R., Diaz, Lorena, Reyes, Jinnethe, Cruz, Melissa R., Pemberton, Orville, Nguyen, April H., Siegel, Sara D., Planet, Paul J., Narechania, Apurva, Latorre, Mauricio, Rios, Rafael, Singh, Kavindra V., Ton-That, Hung, Garsin, Danielle A., Tran, Truc T., Shamoo, Yousif, Arias, Cesar A |
| بيانات النشر: | National Academy of Sciences Proceedings of the National Academy of Sciences |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Enterococos resistentes a la vancomicina, Farmacorresistencia microbiana, Estructuras de la membrana celular, Antibiotic resistance, Enterococcus faecalis, Daptomycin, Cell membrane adaptation, Antimicrobial, Peptides |
| الوصف: | Bacteria have developed several evolutionary strategies to protect their cell membranes (CMs) from the attack of antibiotics and antimicrobial peptides (AMPs) produced by the innate immune system, including remodeling of phospholipid content and localization. Multidrug-resistant Enterococcus faecalis, an opportunistic human pathogen, evolves resistance to the lipopeptide daptomycin and AMPs by diverting the antibiotic away from critical septal targets using CM anionic phospholipid redistribution. The LiaFSR stress response system regulates this CM remodeling via the LiaR response regulator by a previously unknown mechanism. Here, we characterize a LiaR-regulated protein, LiaX, that senses daptomycin or AMPs and triggers protective CM remodeling. LiaX is surface exposed, and in daptomycin-resistant clinical strains, both LiaX and the N-terminal domain alone are released into the extracellular milieu. The N-terminal domain of LiaX binds daptomycin and AMPs (such as human LL-37) and functions as an extracellular sentinel that activates the cell envelope stress response. The C-terminal domain of LiaX plays a role in inhibiting the LiaFSR system, and when this domain is absent, it leads to activation of anionic phospholipid redistribution. Strains that exhibit LiaX-mediated CM remodeling and AMP resistance show enhanced virulence in the Caenorhabditis elegans model, an effect that is abolished in animals lacking an innate immune pathway crucial for producing AMPs. In conclusion, we report a mechanism of antibiotic and AMP resistance that couples bacterial stress sensing to major changes in CM architecture, ultimately also affecting host–pathogen interactions. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1091-6490 |
| العلاقة: | Proceedings of the National Academy of Sciences, 1091-6490, Vol 116, Núm 52, pag 26925–26932; https://www.pnas.org/content/116/52/26925Test; http://hdl.handle.net/20.500.12495/2161Test; https://doi.org/10.1073/pnas.1916037116Test; instname:Universidad El Bosque; reponame: Repositorio Institucional Universidad El Bosque; repourl:https://repositorio.unbosque.edu.coTest |
| DOI: | 10.1073/pnas.1916037116 |
| الإتاحة: | https://doi.org/20.500.12495/2161Test https://doi.org/10.1073/pnas.1916037116Test https://hdl.handle.net/20.500.12495/2161Test |
| حقوق: | Attribution-NonCommercial-NoDerivatives 4.0 International ; http://creativecommons.org/licenses/by-nc-nd/4.0Test/ ; Acceso abierto ; info:eu-repo/semantics/openAccess ; http://purl.org/coar/access_right/c_abf184Test |
| رقم الانضمام: | edsbas.9FF0596B |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 10916490 |
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| DOI: | 10.1073/pnas.1916037116 |