Genetic variation of staphylococcal LukAB toxin determines receptor tropism.
Nat Microbiol
; 6(6): 731-745, 2021 06.
Article
en En
| MEDLINE
| ID: mdl-33875847
ABSTRACT
Staphylococcus aureus has evolved into diverse lineages, known as clonal complexes (CCs), which exhibit differences in the coding sequences of core virulence factors. Whether these alterations affect 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. Together, this work advances our understanding of an important S. aureus toxin and underscores the importance of considering genetic variation in characterizing virulence factors and understanding the tug of war between pathogens and the host.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Infecciones Estafilocócicas
/
Staphylococcus aureus
/
Proteínas Bacterianas
/
Canales Iónicos
/
Leucocidinas
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Nat Microbiol
Año:
2021
Tipo del documento:
Article