Bacterial effectors are proteins secreted by pathogenic bacteria into the cells of their host, usually using a type 3 secretion system (TTSS/T3SS), a type 4 secretion system (TFSS/T4SS) or a Type VI secretion system (T6SS). Some bacteria inject only a few effectors into their host’s cells while others may inject dozens or even hundreds. Effector proteins may have many different activities, but usually help the pathogen to invade host tissue, suppress its immune system, or otherwise help the pathogen to survive. Effector proteins are usually critical for virulence. For instance, in the causative agent of plague (Yersinia pestis), the loss of the T3SS is sufficient to render the bacteria completely avirulent, even when they are directly introduced into the bloodstream. Gram negative microbes are also suspected to deploy bacterial outer membrane vesicles to translocate effector proteins and virulence factors via a membrane vesicle trafficking secretory pathway, in order to modify their environment or attack/invade target cells, for example, at the host-pathogen interface.
Diversity
Many pathogenic bacteria are known to have secreted effectors but for most species the exact number is unknown. Once a pathogen genome has been sequenced, effectors can be predicted based on protein sequence similarity, but such predictions are not always precise. More importantly, it is difficult to prove experimentally that a predicted effector is actually secreted into a host cell because the amount of each effector protein is tiny. For instance, Tobe et al. (2006) predicted more than 60 effectors for pathogenic E. coli but could only show for 39 that they are secreted into human Caco-2 cells. Finally, even within the same bacterial species, different strains often have different repertoires of effectors. For instance, the plant pathogen Pseudomonas syringae has 14 effectors in one strain, but more than 150 have been found in multiple different strains.
Mechanism of action
Given the diversity of effectors, they affect a wide variety of intracellular processes. The T3SS effectors of pathogenic E. coli, Shigella, Salmonella, and Yersinia regulate actin dynamics to facilitate their own attachment or invasion, subvert endocytic trafficking, block phagocytosis, modulate apoptotic pathways, and manipulate innate immunity as well as host responses.
Phagocytosis. Phagocytes are immune cells that can recognize and "eat" bacteria. Phagocytes recognize bacteria directly [e.g., through the so-called scavenger receptor A which recognizes bacterial lipopolysaccharide (LPS) ] or indirectly through antibodies (IgG) and complement proteins (C3bi) which coat the bacteria and are recognized by the Fcγ receptors and integrinαmβ2 (complement receptor 3). For instance, intracellular Salmonella and Shigella escape phagocytic killing through manipulation of endolysosomal trafficking (see there). Yersinia predominantly survives extracellularly using the translocation of effectors to inhibit cytoskeletal rearrangements and thus phagocytosis. EPEC/EHEC inhibit both transcytosis through M cells and internalization by phagocytes. Yersinia inhibits phagocytosis through the concerted actions of several effector proteins, including YopE which acts as a RhoGAP and inhibits Rac-dependent actin polymerization.
Endocytic trafficking. Several bacteria, including Salmonella and Shigella, enter the cell and survive intracellularly by manipulating the endocytic pathway. Once internalized by host cells Salmonella subverts the endolysosome trafficking pathway to create a Salmonella-containing vacuole (SCV), which is essential for its intracellular survival. As the SCVs mature they travel to the microtubule organizing center (MTOC), a perinuclear region adjacent to the Golgi, where they produce Salmonella induced filaments (Sifs) dependent on the T3SS effectors SseF and SseG. By contrast, internalized Shigella avoids the endolysosome system by rapidly lysing its vacuole through the action of the T3SS effectors IpaB and C although the details of this process are poorly understood.
Secretory pathway. Some pathogens, such as EPEC/EHEC disrupt the secretory pathway. For instance, their effector EspG can reduce the secretion of interleukin-8 (IL-8), and thus affect the immune system (immunomodulation). EspG functions as a Rab GTPase-activating protein (Rab-GAP), trapping Rab-GTPases in their inactive GDP bound form, and reducing ER–Golgi transport (of IL-8 and other proteins).