Bacterial Type IV Secretion Systems: Versatile Virulence Machines

Abstract

Many bacterial pathogens employ multicomponent protein complexes to deliver macromolecules directly into their eukaryotic host cell to promote infection. Some Gram-negative pathogens use a versatile type IV secretion system (T4SS) that can translocate DNA or proteins into host cells. T4SSs represent major bacterial virulence determinants and have recently been the focus of intense research efforts designed to better understand and combat infectious diseases. Interestingly, although the two major classes of T4SSs function in a similar manner to secrete proteins, the translocated “effectors” vary substantially from one organism to another. In fact, differing effector repertoires likely contribute to organism-specific host cell interactions and disease outcomes. In this review, we discuss the current state of T4SS research, with an emphasis on intracellular bacterial pathogens of humans and the diverse array of translocated effectors used to manipulate host cells.

Characterization of the Translocation-competent Complex between the Helicobacter pylori Oncogenic Protein CagA and the Accessory Protein CagF

“…In diverse bacteria, T4SSs are not only used for translocation of effector molecules but also for conjugation and DNA release (1,2). Most substrates are translocated through the system by signal sequences carried either by the effector proteins themselves or by relaxase proteins used in DNA transfer (1,31).…”

“…Type IV secretion systems (T4SS) 3 are important virulence factor delivery systems that are used by several Gram-negative bacteria to inject effector molecules directly into host cells where they elicit changes in cell function, immune response, and therefore the local environment, that aid in colonization (1,2). Helicobacter pylori reside within the human stomach.…”

Pathogenesis of Human Enterovirulent Bacteria: Lessons from Cultured, Fully Differentiated Human Colon Cancer Cell Lines

“…The type III secretion system (T3SS), composed of more than 20 different proteins which form a large supramolecular structure crossing the bacterial cell envelope, includes the bacterial flagellum and the virulence-associated injectisome, which are two complex, structurally related nanomachines that enterovirulent bacteria use for locomotion and for the translocation of virulence factors into eukaryotic host cells, respectively (273)(274)(275)(276). The type IV secretion system is a translocation pore involving the coordinate assembly of core complex proteins, including VirB3 to VirB10, which assembles with VirD4 for substrate recruitment and which, after activation, secretes the substrate (277)(278)(279). In addition, by association of the core complex proteins with the VirB11 protein, a pilus formed of VirB2 and VirB5 proteins assembles.…”

Structural basis for the recruitment and activation of the Legionella phospholipase VipD by the host GTPase Rab5

“…Intravacuolar pathogens use specialized translocation devices such as type IV secretion systems (T4SS) to deliver virulence proteins, so-called effectors, across the bacterial and host cell membrane into the cytosol of the infected cell (1)(2)(3). Many of the translocated effectors studied to date alter cellular events such as vesicle trafficking, apoptosis, autophagy, protein ubiquitylation, or protein synthesis, among others, thereby creating conditions that support intracellular survival and replication of the microbe (4,5).…”