Expanding Role of Type II Secretion in Bacterial Pathogenesis and Beyond

Abstract

Type II secretion (T2S) is one means by which Gram-negative pathogens secrete proteins into the extracellular milieu and/or host organisms. Based upon recent genome sequencing, it is clear that T2S is largely restricted to the Proteobacteria, occurring in many, but not all, genera in the Alphaproteobacteria, Betaproteobacteria, Gammaproteobacteria, and Deltaproteobacteria classes. Prominent human and/or animal pathogens that express a T2S system(s) include Acinetobacter baumannii, Burkholderia pseudomallei, Chlamydia trachomatis, Escherichia coli, Klebsiella pneumoniae, Legionella pneumophila, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Vibrio cholerae, and Yersinia enterocolitica T2S-expressing plant pathogens include Dickeya dadantii, Erwinia amylovora, Pectobacterium carotovorum, Ralstonia solanacearum, Xanthomonas campestris, Xanthomonas oryzae, and Xylella fastidiosa T2S also occurs in nonpathogenic bacteria, facilitating symbioses, among other things. The output of a T2S system can range from only one to dozens of secreted proteins, encompassing a diverse array of toxins, degradative enzymes, and other effectors, including novel proteins. Pathogenic processes mediated by T2S include the death of host cells, degradation of tissue, suppression of innate immunity, adherence to host surfaces, biofilm formation, invasion into and growth within host cells, nutrient assimilation, and alterations in host ion flux. The reach of T2S is perhaps best illustrated by those bacteria that clearly use it for both environmental survival and virulence; e.g., L. pneumophila employs T2S for infection of amoebae, growth within lung cells, dampening of cytokines, and tissue destruction. This minireview provides an update on the types of bacteria that have T2S, the kinds of proteins that are secreted via T2S, and how T2S substrates promote infection.

Keywords: Legionella; T2S; Vibrio; animal pathogens; degradative enzymes; human pathogens; plant pathogens; toxins; type II secretion.

FIG 1

Representative distribution of T2S genes among the Proteobacteria. An unrooted phylogenetic tree of the Proteobacteria and several other bacteria was constructed with aligned 16S rRNA sequences (65, 66) using standard neighbor-joining methods (67, 68). Genus names are denoted at each leaf. Clades representing the alpha-, beta-, gamma-, delta-, and epsilonproteobacteria are identified by the α, β, γ, δ, and ε Greek symbols. The bar represents the number of nucleotide substitutions per site. Bacteria that have been demonstrated to express a functional T2S system are indicated in green. Representative bacteria that have a complete or nearly complete set of T2S genes but for which functionality has not yet been shown are indicated in red. Representative bacteria that lack T2S genes are indicated in black.

FIG 2

Roles of T2S in V. cholerae and L. pneumophila. (A) More than 20 proteins are secreted via the T2S system of V. cholerae. T2S promotes the environmental survival of extracellular V. cholerae in a variety of ways, including the colonization of biotic surfaces (left side, in blue). This facilitates transmission to the human host, where T2S mediates another set of activities that leads to cholera (right side, in red). (B) More than 25 substrates are handled by the T2S system of L. pneumophila. In the environment, T2S facilitates the spread of L. pneumophila by contributing to planktonic survival, biofilm formation, and intracellular infection of amoebae (left side, in green). Following the inhalation of L. pneumophila, T2S promotes bacterial growth within lung macrophages, which leads to tissue damage and pneumonia (right side, in red).