Type Three Secretion System Effector Translocation: One Step or Two?

recent publication, Akopyan et al. (2011) provide evidence challenging this canonical “one-step” model for the transport of effector proteins, proposing that in Yersinia pseudotuberculosis at least, a “two-step” model of T3SS-dependent protein translocation may be possible. In this “two-step” process, bacterial effectors are first secreted to the surface of the bacterium and then translocated across the host cell membrane in a T3SS-dependent manner. Immunoelectron microscopy showed that Yersinia T3SS effectors YopE and YopH, and the translocator YopD are evenly distributed across the Yersinia surface prior to contact with host cells (Akopyan et al., 2011). It is not uncommon for translocator proteins to be found on the bacterial surface (Ménard et al., 1994; Watarai et al., 1996; Lara-Tejero and Galan, 2009), particularly since the hydrophilic translocator protein forms a tip at the end of the T3SS needle (Mueller et al., 2008). However, previous data employing immunofluorescent microscopy indicated that effector proteins accumulated in the bacterial cytoplasm awaiting exit through the T3SS, and often exhibited polarized localization toward active T3SS needles (Schlumberger et al., 2005; Jaumouille et al., 2008; Winnen et al., 2008). Such data fits with a one-step T3SS translocation model where T3SS substrates are synthesized and stored in the bacterial cytoplasm ready to be fed to the T3SS basal body upon T3SS activation, with subsequent transport through the interior of the needle. While there is no direct evidence for effector transport through the needle, experiments have shown the need for effectors to unfold prior to secretion – indicative of transport though the needle core (Akeda and Galan, 2005). A one-step model would also explain how effectors can be translocated in a hierarchial manner as has been shown for SipA, SopE, and SptP in Salmonella (Winnen et al., 2008; Lara-Tejero et al., 2011). Perhaps the most compelling evidence to support the current Type three secretion system effector translocation: one step or two?