Abstract:
Staphylococcus aureus is a major human and animal pathogen and a common cause of mastitis in cattle.
S. aureus secretes several leukocidins that target bovine neutrophils, crucial effector cells in the defence
against bacterial pathogens. In this study, we investigated the role of staphylococcal leukocidins in the
pathogenesis of bovine S. aureus disease. We show that LukAB, in contrast to the γ-hemolysins, LukED,
and LukMF′, was unable to kill bovine neutrophils, and identified CXCR2 as a bovine receptor for HlgAB
and LukED. Furthermore, we assessed functional leukocidin secretion by bovine mastitis isolates and
observed that, although leukocidin production was strain dependent, LukMF′ was most abundantly
secreted and the major toxin killing bovine neutrophils. To determine the role of LukMF′ in bovine
mastitis, cattle were challenged with high (S1444) or intermediate (S1449, S1463) LukMF′-producing
isolates. Only animals infected with S1444 developed severe clinical symptoms. Importantly, LukM
was produced in vivo during the course of infection and levels in milk were associated with the severity
of mastitis. Altogether, these findings underline the importance of LukMF′ as a virulence factor and
support the development of therapeutic approaches targeting LukMF′ to control S. aureus mastitis in
cattle.
