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Bacteria's hidden weapons: How do effector proteins manipulate host cells?
With the advancement of bacteriology and molecular biology, scientists have gradually unveiled the mystery of bacterial effectors. These effector proteins are the "secret weapons" delivered by pathogenic bacteria to host cells through the secretion system, and they play a crucial role in the bacterial infection process.
Effector proteins usually help pathogens invade host tissues, suppress the immune system, or increase the pathogen's ability to survive.
Many pathogenic bacteria are able to secrete effector proteins, but the exact amounts are unknown for most species. When pathogen genomes are sequenced, effector proteins can be predicted based on protein sequence similarities, but these predictions are not always accurate. More importantly, it is very difficult to experimentally prove that a predicted effector protein is actually secreted into the host cell due to the negligible amount of each effector protein.
Take pathogenic E. coli as an example. Research shows that the bacterium may have more than 60 effector proteins, but only 39 have been confirmed to successfully enter human Caco-2 cells. Even within the same bacterial species, different strains often possess different combinations of effector proteins. For example, the plant pathogenic bacterium Pseudomonas aeruginosa has 14 effector proteins, but the number of effector proteins found in multiple different strains reaches almost 150.
The mechanism of action of effector proteins
The diversity of effector proteins allows them to influence many processes within the host cell. For example, T3SS effector proteins of pathogenic Escherichia coli, Shigella, Salmonella, and Yersinia pestis are able to modulate the actin dynamics of host cells and promote their attachment or invasion. They can also disrupt endocytic trafficking, prevent phagocytosis, and modulate apoptotic pathways and host immune responses.
After pathogens enter host cells, they will use the endocytosis pathway to survive, and some bacteria can even change the process of apoptosis.
For example, phagocytes are immune cells that recognize and "engulf" bacteria. These cells can recognize bacteria directly through something called scavenger receptor A, or indirectly through antibodies and complement proteins. Internal Salmonella and Shigella use interference with endolysosomal trafficking to evade phagocytosis and survive within the host cell. Yersinia pestis, on the other hand, blocks this process by inhibiting cytoskeletal reorganization.
During the endocytic transport process, Salmonella bacteria promote the formation of themselves wrapped in "Salmonella cysts" (SCVs), and as SCVs mature, they move to the microtubule organizing center to further promote bacterial survival. Meanwhile, Shigella evades the endolysosomal system by rapidly lysing the cyst.
In addition to affecting phagocytosis and endocytic transport, the effector proteins of some pathogens can also interfere with the secretory pathway of host cells. For example, the effector protein EspG of enteropathogenic Escherichia coli can reduce the secretion of interleukin-8 in host cells, thus affecting the immune response. This effector protein, like other effector proteins, has a strong inhibitory effect on the host immune system.
Many pathogenic bacteria have developed mechanisms to prevent host cell apoptosis in order to maintain their living environment.
For example, the effector proteins NleH and NleF of enteropathogenic Escherichia coli prevent host cell apoptosis. In addition, the Shigella effector proteins IpgD and OspG also have similar functions. These effector proteins can prevent host cells from undergoing apoptotic response by interfering with the NF-kB pathway. Although many effector proteins play a key role in resisting host cell death, some effector proteins induce cell death, such as the role of the EHEC effector proteins EspF, EspH, and Cif.
Means of anti-immune response
Pathogenic bacteria evade the host's immune response through various ways, one of the main means is to interfere with the NF-kB signaling pathway in host cells. A variety of effector proteins can effectively inhibit the activation of the NF-kB pathway. For example, the effector protein NleC of enteropathogenic Escherichia coli prevents the production of IL-8 by cleaving components of NF-kB. Similarly, YopE and YopP of Yersinia pestis prevent the activation of NF-kB, which plays an important role in preventing inflammatory responses.
With the in-depth study of bacterial effector proteins, we have a more comprehensive understanding of their role in pathogenic infection. Will this change the way we think about treating infectious diseases in the future?
