Genetic variation of staphylococcal LukAB toxin determines receptor tropism
| Autor: | Victor J. Torres, Kristina M. Boguslawski, Sofya S. Perelman, Nikollaq Vozhilla, Damian C. Ekiert, Ahmed M Moustafa, Adil Mohamed, Kayan Tam, David B. A. James, Rachel A Prescott, Bo Shopsin, Rita Chan, Chase W. Nelson, Apurva Narechania, Miranda B Pawline, Sang Yong Kim, Erin E Zwack, Meike Dittmann, Paul J. Planet, Juliana K Ilmain, Gira Bhabha, Sergei B. Koralov |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Microbiology (medical)
Staphylococcus aureus leukocidin Immunology Virulence LukAB MRSA Biology medicine.disease_cause Applied Microbiology and Biotechnology Microbiology Article Ion Channels 03 medical and health sciences Bacterial Proteins Leukocidins Bloodstream infection Genetic variation Genetics medicine Animals Humans Receptor Tropism 030304 developmental biology 0303 health sciences Phagocytes CD11b Antigen HVCN1 030306 microbiology Toxin Genetic Variation Cell Biology Staphylococcal Infections Mice Inbred C57BL Integrin alpha M biology.protein toxin receptor |
| Zdroj: | Nature microbiology |
| ISSN: | 2058-5276 |
| Popis: | Staphylococcus aureus have evolved into diverse lineages, known as clonal complexes (“CC”), which exhibit differences in the coding sequences of core virulence factors. Whether these alterations impact functionality is poorly understood. Here, we studied the highly polymorphic pore-forming toxin LukAB. We discovered that the LukAB toxin variants produced by S. aureus CC30 and CC45 kill human phagocytes regardless of whether CD11b, the previously established LukAB receptor, is present, and instead target the human hydrogen voltage-gated channel 1 (HVCN1). Biochemical studies identified the domain within human HVCN1 that drives LukAB species specificity, enabling the generation of humanized HVCN1 mice with enhanced susceptibility to CC30 LukAB and to bloodstream infection caused by CC30 S. aureus strains. Altogether, this work advances our understanding of an important S. aureus toxin and underscores the importance of considering genetic variation to characterizing virulence factors and understand the tug of war between pathogens and the host. |
| Databáze: | OpenAIRE |
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