Type II Secretion and Pathogenesis

Abstract

Extracellular secretion of proteins is regarded as a major virulence mechanism in bacterial infection. Proteins destined for the extracellular environment of gram-negative bacteria have to cross two membranes during their journey across the bacterial cell envelope. This involves translocation across the cytoplasmic membrane and the outer membrane, which are separated by the periplasmic compartment and the peptidoglycan layer. Several highly specialized pathways have evolved for this purpose. The type II secretion pathway is one such system that is encoded by at least 12 genes and specifically supports the transport of a group of seemingly unrelated proteins across the outer membrane. In order for these proteins to enter the type II secretion pathway, they have to first translocate across the cytoplasmic membrane via the Sec system and then fold into a translocation competent conformation in the periplasm. Proteins secreted by the type II pathway include proteases, cellulases, pectinases, phospholipases, lipases, and toxins. In general, these proteins are associated with destruction of various tissues, which contributes to cell damage and disease. Expression of the genes for these proteins and, in some cases, the secretion genes themselves are under quorum-sensing control or are strictly regulated by the environment at the site of colonization. This type of regulation results in controlled secretion of virulence factors that will only occur when the bacteria have reached their correct location and obtained a critial mass. Species identified to date as harboring type II secretion genes are members of proteobacteria, and most of them appear to be extracellular pathogens. Genome sequencing of bacterial pathogens continues to identify additional species that contain DNA highly homologous to the type II secretion genes, suggesting that this pathway is widely distributed within the proteobacterial family. This review discusses the identification of additional type II secretion genes and the expansion of the type II secretion gene family. The regulation of type II secretion and its role in disease are also addressed. Finally, the finding that a component of the type II secretion pathway in Vibrio cholerae can also support bacteriophage extrusion is discussed.

Virulence determinants in the obligate intracellular pathogen Chlamydia trachomatis revealed by forward genetic approaches

“…Five Gsp proteins of the canonical T2S apparatus are conserved in the Chlamydiae. (B) The ATPase GspE is essential for T2S in eubacteria (18) and the G425 position is invariant among widely diverse bacterial species. Grn4 mutants contain a GspE G425E mutation.…”

Remodeling a DNA-binding protein as a specific in vivo inhibitor of bacterial secretin PulD

“…We focused our attention on the T2SS, a secretion pathway essential for several important human bacterial pathogens such as Vibrio cholerae, in which it secretes proteases, chitinases, and cholera toxin (18). The pullulanase T2SS from K. oxytoca, of which secretin PulD is part, can be transferred in E. coli (16), and is thus a good model to study secretion mechanisms.…”

Differences in adherence and virulence gene expression between two outbreak strains of enterohaemorrhagic Escherichia coli O157 : H7

“…The pO157- borne type II secretion system, encoded by the etpC-O polycistron, is represented by 12 probes on the microarray, nine of which indicated upregulation of target genes (etpEFGHIJKMN) in TW14359. The type II apparatus secretes several factors that influence colonization (Sandkvist, 2001). The transcription of one such gene, stcE (tagA), which encodes a metalloprotease that contributes to intimate adherence (Grys et al, 2005), was elevated in TW14359.…”