Effector Glycosyltransferases in Legionella

Abstract

Legionella causes severe pneumonia in humans. The pathogen produces an array of effectors, which interfere with host cell functions. Among them are the glucosyltransferases Lgt1, Lgt2 and Lgt3 from L. pneumophila. Lgt1 and Lgt2 are produced predominately in the postexponential phase of bacterial growth, while synthesis of Lgt3 is induced mainly in the lag-phase before intracellular replication of bacteria starts. Lgt glucosyltransferases are structurally similar to clostridial glucosylating toxins. The enzymes use UDP-glucose as a donor substrate and modify eukaryotic elongation factor eEF1A at serine-53. This modification results in inhibition of protein synthesis and death of target cells.In addition to Lgts, Legionella genomes disclose several genes, coding for effector proteins likely to possess glycosyltransferase activities, including SetA (subversion of eukaryotic vesicle trafficking A), which influences vesicular trafficking in the yeast model system and displays tropism for late endosomal/lysosomal compartments of mammalian cells. This review mainly discusses recent results on the structure-function relationship of Lgt glucosyltransferases.

The chaperonin TRiC/CCT is essential for the action of bacterial glycosylating protein toxins like Clostridium difficile toxins A and B

“…Our data provide insight into the cellular actions of glucosylating toxins. a glucosyltransferase that is translocated into eukaryotic cells by the Dot/Icm type-IV secretion system (32)(33)(34). Glucosyltransferase SetA modified ∼60and ∼40-kDa proteins in Jurkat cell lysate in the presence of UDP-[ 14 C]glucose.…”

Domain organization of Legionella effector SetA

“…To this end, Legionella produces hundreds of effector proteins, which are secreted by a type IV secretion system into the host cell cytosol. Only a few of these effector proteins are described in greater detail (Ninio and Roy, 2007; Ensminger and Isberg, 2009; Isberg et al ., 2009; Hubber and Roy, 2010; Belyi et al ., 2011).…”

Elongation Factor 1A Is the Target of Growth Inhibition in Yeast Caused by Legionella pneumophila Glucosyltransferase Lgt1

“…Among L. pneumophila effectors are cytotoxic glucosyltransferases of the Lgt family (6). These enzymes use UDPglucose as a cofactor and target eukaryotic substrates by covalent attachment of a glucosyl moiety (7).…”