Structural biology of the invasion arsenal of Gram-negative bacterial pathogens

In the last several years, there has been a tremendous progress in the understanding of host-pathogen interactions and the mechanisms by which bacterial pathogens modulate behavior of the host cell. Pathogens use secretion systems to inject a set of proteins, called effectors, into the cytosol of the host cell. These effectors are secreted in a highly regulated, temporal manner and interact with host proteins to modify a multitude of cellular processes. The number of effectors varies between pathogens from similar to 30 to as many as similar to 350. The functional redundancy of effectors encoded by each pathogen makes it difficult to determine the cellular effects or function of individual effectors, since their individual knockouts frequently produce no easily detectable phenotypes. Structural biology of effector proteins and their interactions with host proteins, in conjunction with cell biology approaches, has provided invaluable information about the cellular function of effectors and underlying molecular mechanisms of their modes of action. Many bacterial effectors are functionally equivalent to host proteins while being structurally divergent from them. Other effector proteins display new, previously unobserved functionalities. Here, we summarize the contribution of the structural characterization of effectors and effector-host protein complexes to our understanding of host subversion mechanisms used by the most commonly investigated Gram-negative bacterial pathogens. We describe in some detail the enzymatic activities discovered among effector proteins and how they affect various cellular processes.

Automated summary

The past few years have seen significant progress in understanding host-pathogen interactions and how bacterial pathogens manipulate host cell behavior through the use of effector proteins. Effector proteins, secreted in a regulated manner, interact with host proteins to modify cellular processes. Structural characterization of effectors and their interactions with host proteins has provided valuable insights into the mechanisms used by Gram-negative bacterial pathogens to subvert host cells.