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2015 ; 6
(3
): e00335
Nephropedia Template TP
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Bovine Staphylococcus aureus Secretes the Leukocidin LukMF To Kill Migrating
Neutrophils through CCR1
#MMPMID26045537
Vrieling M
; Koymans KJ
; Heesterbeek DA
; Aerts PC
; Rutten VP
; de Haas CJ
; van Kessel KP
; Koets AP
; Nijland R
; van Strijp JA
mBio
2015[Jun]; 6
(3
): e00335
PMID26045537
show ga
Although Staphylococcus aureus is best known for infecting humans,
bovine-specific strains are a major cause of mastitis in dairy cattle. The
bicomponent leukocidin LukMF', exclusively harbored by S. aureus of ruminant
origin, is a virulence factor associated with bovine infections. In this study,
the molecular basis of the host specificity of LukMF' is elucidated by
identification of chemokine receptor CCR1 as its target. Bovine neutrophils, the
major effector cells in the defense against staphylococci, express significant
cell surface levels of CCR1, whereas human neutrophils do not. This causes the
particular susceptibility of bovine neutrophils to pore formation induced by
LukMF'. Bovine S. aureus strains produce high levels of LukMF' in vitro. In
culture supernatant of the mastitis field isolate S1444, LukMF' was the most
important cytotoxic agent for bovine neutrophils. In a fibrin gel matrix, the
effects of the in situ secreted toxins on neutrophils migrating toward S. aureus
were visualized. Under these physiological ex vivo conditions, bovine S. aureus
S1444 efficiently killed approaching neutrophils at a distance through secretion
of LukMF'. Altogether, our findings illustrate the coevolution of pathogen and
host, provide new targets for therapeutic and vaccine approaches to treat
staphylococcal diseases in the cow, and emphasize the importance of
staphylococcal toxins in general. IMPORTANCE: This study explains the mechanism
of action of LukMF', a bicomponent toxin found in bovine lineages of S. aureus
that is associated with mastitis in cattle. At a molecular level, we describe how
LukMF' can specifically kill bovine neutrophils. Here, we demonstrate the
contribution of toxins in the determination of host specificity and contribute to
the understanding of mechanisms of coevolution of pathogen and host. Our study
provides new targets that can be used in therapeutic and vaccine approaches to
treat staphylococcal diseases in the cow. We also demonstrate the importance of
toxins in specific elimination of immune cells, which has broader implications,
especially in human infections.