Type II Secretion and Legionella Virulence

Abstract

Type II secretion (T2S) is one of six systems that can occur in Gram-negative bacteria for the purpose of secreting proteins into the extracellular milieu and/or into host cells. This chapter will describe the T2S system of Legionella pneumophila. Topics to be covered include the genetic basis of T2S in L. pneumophila, the numbers (>25), types, and novelties of Legionella proteins that are secreted via T2S, and the many ways in which T2S and its substrates promote L. pneumophila physiology, ecology, and virulence. Within the aquatic environment, T2S plays a major role in L. pneumophila intracellular infection of multiple types of (Acanthamoeba, Hartmannella, and Naegleria) amoebae. Within the mammalian host, T2S promotes bacterial persistence in lungs, intracellular infection of both macrophages and epithelial cells, and a dampening of the host innate immune response. In this context, T2S may represent a potential target for both industrial and biomedical application.

Life Stage-specific Proteomes of Legionella pneumophila Reveal a Highly Differential Abundance of Virulence-associated Dot/Icm effectors

“…The eleven most abundant proteins contributed to 53% of the total extracellular protein quantity. Remarkably, eight of those were substrates of the Lsp T2SS (zinc metalloproteinase ProA, aminopeptidase LapA, chitinase ChiA, endoglucanase CelA, tail-fiber-like protein SclB, hypothetical proteins Lpg1832, Lpg0873, Lpg0956), and only two of which (ChiA, Lpg0956) were differentially abundant, specifically PE-up (20,25). In addition, we quantified 10 more T2SS substrates and therefore quantified the almost entire known T2SS secretome (except NttA/Lpg1385 and IcmX/ Lpg2889) of L. pneumophila (20,25) (Fig.…”

“…The further PE-up extr majorly included 8 proteins without assigned function (Lpg2220, Lpg1647, Lpg1645, Lpg0957, Lpg0301 Lpg1318, Lpg2206, Lpg2246), 5 T2SS substrates (chitinase ChiA, phospholipase A/acyltransferase PlaC, hypothetical protein Lpg0956, Lpg0189, Lpg0264), three Dot/Icm effectors (LegP, Lpg1667, Lpg2443) and Dot/Icm apparatus core complex protein DotC, as well as further (in addition to FlgK) motility-related proteins (FliC, FliD) (26,70,(95)(96)(97). The phase-stable extracellular proteome (42 proteins) included 13 T2SS substrates (phospholipase C PlcA, NttC, endoglucanase CelA, lysophospholipase A PlaA, T2 ribonuclease SrnA, NttB, Lpg1832, SclB, aminopeptidases LapB, LapA, zinc metalloprotease ProA, major acid phosphatase Map, Lpg0873), five Dot/Icm effectors (LegY/GamA which was also detected as T2SS substrate (25), LirB, MavL, LegS, Lpg0041), three proteins involved in carbon and energy metabolism (enolase Eno, thioredoxin reductase TrxB1, xylanase-like protein YjeA), as well as nine functionally unassigned proteins (Fig. 5, supplemental Fig.…”

“…Several protein secretion systems of L. pneumophila are associated with bacterial virulence, such as the Defect in organelle trafficking/Intracellular multiplication (Dot/Icm) type IVB secretion system (T4BSS), the Legionella type II secretion pathway (Lsp) (T2SS), the type I (Lss), and the Twin-arginine translocation (Tat) systems (15,(17)(18)(19)(20)(21)(22)(23)(24). More than 300 and 25 proteins are translocated into the host cell by the T4BSS or are exported by the T2SS, respectively (18,25). Previous proteomics studies gave an insight into the variety of L. pneumophila proteins present in the culture supernatant and on their dependence on type II secretion, Tat secretion, or export via outer membrane vesicles.…”

“…Previous proteomics studies gave an insight into the variety of L. pneumophila proteins present in the culture supernatant and on their dependence on type II secretion, Tat secretion, or export via outer membrane vesicles. In those studies, 2DE/MS analysis was used and identified at least 20 type II-secreted proteins, 20 proteins with differential abundance in wild type and a Tat mutant as well as 181 culture supernatant proteins of which 33 specifically were associated with outer membrane vesicles (20,(25)(26)(27)(28). Furthermore, in a recent study by Hoffmann et al, the proteome of intracellular L. pneumophila 1h post infection was analyzed by means of 1D gel electrophoresis and subsequent liquid chromatography-MS/MS (29).…”

Prevalence of 7 virulence genes of <i>Legionella</i> strains isolated from environmental water sources of public facilities and sequence types diversity of <i>L. pneumopila</i> strains in Macau

“…In the present study, seven virulence genes (flaA, pilE, asd, mip, mompS, proA and neuA) responsible for the expression of adherence, invasion, colonization and cytotoxin production (6,7), were detected in all 55 strains isolated from Macau. For comparison, the PCR and the real-time PCR were applied to detect the genes simultaneously.…”