Type III machines of pathogenic yersiniae secrete virulence factors into the extracellular milieu

Gram-negative bacteria use type III machines to inject toxic proteins into the cytosol of eukaryotic cells. Pathogenic Yersinia species export 14 Yop proteins by the type III pathway and some of these, named effector Yops, ar e targeted into macrophages, thereby preventing phagocytosis and allowing b acterial replication within lymphoid tissues. Hitherto, YopB/YopD were thou ght to insert into the plasma membrane of macrophages and to promote the im port of effector Yops into the eukaryotic cytosol. We show here that the ty pe III machines of yersiniae secrete three proteins into the extracellular milieu (YopB, YopD and YopR). Although intrabacterial YopD is required for the injection of toxins into eukaryotic cells, secreted YopB, YopD and YopR are dispensable for this process. Nevertheless, YopB, YopD and YopR are es sential for the establishment of Yersinia infections in a mouse model syste m, suggesting that type III secretion machines function to deliver virulenc e factors into the extracellular milieu also.