A Small Membrane Stabilizing Protein Critical to the Pathogenicity of Staphylococcus aureus
| Autor: | Alaa Abdulaziz Alnahari, Ruth C. Massey, Maisem Laabei, Kate J. Heesom, Michael Otto, Rachel M. McLoughlin, Chih-Lung Fu, Eric P. Skaar, Seána Duggan, Eóin C O'Brien, Keenan A. Lacey, Leann Bacon |
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| Rok vydání: | 2020 |
| Předmět: |
Proteomics
0301 basic medicine Erythrocytes THP-1 Cells Bacteremia Human pathogen medicine.disease_cause Hemolysin Proteins Homeostasis Pathogen Mice Inbred BALB C Virulence Staphylococcal Infections 3. Good health Infectious Diseases Staphylococcus aureus cytotoxins Staphylococcal Skin Infections Functional genomics alpha-Defensins Staphylococcal Toxoid Virulence Factors Iron Bacterial Toxins 030106 microbiology Immunology Heme Biology Microbiology 03 medical and health sciences Antibiotic resistance Phagocytosis medicine Animals Humans Secretion immune evasion Innate immune system Gene Expression Profiling Molecular Pathogenesis Mice Inbred C57BL 030104 developmental biology Gene Expression Regulation A549 Cells Mutation iron homeostasis Parasitology |
| Zdroj: | Duggan, S, Laabei, M, Alnahari, A, O'Brien, E T, Lacey, K, Bacon, L, Heesom, K J, Fu, C-L, Otto, M, Skaar, E, McLoughlin, R M & Massey, R C 2020, ' A small membrane stabilising protein critical to the pathogenicity of Staphylococcus aureus ', Infection and Immunity . https://doi.org/10.1128/IAI.00162-20 Infection and Immunity |
| ISSN: | 1098-5522 0019-9567 |
| Popis: | Staphylococcus aureus is a major human pathogen, and the emergence of antibiotic-resistant strains is making all types of S. aureus infections more challenging to treat. With a pressing need to develop alternative control strategies to use alongside or in place of conventional antibiotics, one approach is the targeting of established virulence factors. However, attempts at this have had little success to date, suggesting that we need to better understand how this pathogen causes disease if effective targets are to be identified. Staphylococcus aureus is a major human pathogen, and the emergence of antibiotic-resistant strains is making all types of S. aureus infections more challenging to treat. With a pressing need to develop alternative control strategies to use alongside or in place of conventional antibiotics, one approach is the targeting of established virulence factors. However, attempts at this have had little success to date, suggesting that we need to better understand how this pathogen causes disease if effective targets are to be identified. To address this, using a functional genomics approach, we have identified a small membrane-bound protein that we have called MspA. Inactivation of this protein results in the loss of the ability of S. aureus to secrete cytolytic toxins, protect itself from several aspects of the human innate immune system, and control its iron homeostasis. These changes appear to be mediated through a change in the stability of the bacterial membrane as a consequence of iron toxicity. These pleiotropic effects on the ability of the pathogen to interact with its host result in significant impairment in the ability of S. aureus to cause infection in both a subcutaneous and sepsis model of infection. Given the scale of the effect the inactivation of MspA causes, it represents a unique and promising target for the development of a novel therapeutic approach. |
| Databáze: | OpenAIRE |
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