Secreted-in-xylem (SIX) proteins of the vascular wilt pathogen Fusarium 
oxysporum f. sp. lycopersici are secreted during infection of tomato and 
function in virulence or avirulence. F. oxysporum formae speciales have specific 
host ranges but the roles of SIX proteins in diverse hosts are unknown. We 
identified homologs of F. oxysporum f. sp. lycopersici SIX1, SIX4, SIX8, and 
SIX9 in the genome of Arabidopsis infecting isolate Fo5176. A SIX4 homolog 
(termed Fo5176-SIX4) differed from that of F. oxysporum f. sp. lycopersici 
(Fol-SIX4) by only two amino acids, and its expression was induced during 
infection of Arabidopsis. Transgenic Arabidopsis plants constitutively 
expressing Fo5176-SIX4 had increased disease symptoms with Fo5176. Conversely, 
Fo5176-SIX4 gene knock-out mutants (Δsix4) had significantly reduced virulence 
on Arabidopsis, and this was associated with reduced fungal biomass and host 
jasmonate-mediated gene expression, the latter known to be essential for host 
symptom development. Full virulence was restored by complementation of Δsix4 
mutants with either Fo5176-SIX4 or Fol-SIX4. Thus, Fo5176-SIX4 contributes 
quantitatively to virulence on Arabidopsis whereas, in tomato, Fol-SIX4 acts in 
host specificity as both an avirulence protein and a suppressor of other 
race-specific resistances. The strong sequence conservation for SIX4 in F. 
oxysporum f. sp. lycopersici and Fo5176 suggests a recent common origin.