Fungal interactions with plant roots, either beneficial or detrimental, have a crucial impact on agriculture and ecosystems. The cosmopolitan plant pathogen Fusarium oxysporum (Fo) provokes vascular-wilt disease in more than a hundred different crops. On angiosperms (flowering plants), Fo exhibits exquisite adaptation to the plant xylem niche as well as host-specific pathogenicity in form of wilting, both of which are conferred by effectors secreted in xylem (SIX) and encoded on lineage-specific genomic regions. However, such isolates also can colonize the roots of other plants asymptomatically as endophytes or even protect them against pathogenic strains. The molecular determinants of endophytic multi-host compatibility are largely unknown. Moreover, the strategies that enable these pathogens to exploit deeper tissues such as xylem and what led to the emergence of such systemic infections in plants remains elusive....