Abstract

Type III secretion systems are used by many Gram-negative bacterial pathogens to inject proteins, known as effectors, into the cytosol of host cells. These virulence factors interfere with a diverse array of host signal transduction pathways and cellular processes. Many effectors have catalytic activities to promote post-translational modifications of host proteins. This review focuses on a family of effectors with glycosyltransferase activity that catalyze addition of N-acetyl-d-glucosamine to specific arginine residues in target proteins, leading to reduced NF-κB pathway activation and impaired host cell death. This family includes NleB from Citrobacter rodentium, NleB1 and NleB2 from enteropathogenic and enterohemorrhagic Escherichia coli, and SseK1, SseK2, and SseK3 from Salmonella enterica. First, we place these effectors in the general framework of the glycosyltransferase superfamily and in the particular context of the role of glycosylation in bacterial pathogenesis. Then, we provide detailed information about currently known members of this family, their role in virulence, and their targets.

Highlights

  • Type III secretion systems (T3SSs) are fundamental tools for the interaction between many pathogenic and symbiotic Gram-negative bacteria and their hosts

  • Effectors can be classified in four non-mutually exclusive categories according to their mechanisms of activity [5]: (i) effectors that mediate their activities through physical interactions with host targets; (ii) effectors that use functional or structural mimicry to alter host cell processes; (iii) effectors that promote post-translational modifications of host proteins; and (iv) effectors with protease activity

  • This review focuses on a specific family of T3SS effectors with glycosyltransferase activity that are found in Salmonella enterica and in attaching/effacing (A/E) pathogens

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Summary

Introduction

Type III secretion systems (T3SSs) are fundamental tools for the interaction between many pathogenic and symbiotic Gram-negative bacteria and their hosts. T3SSs, known as injectisomes, span the bacterial inner and outer membranes and form injection nanomachines that deliver proteins, known as effectors, into target eukaryotic cells to modulate a variety of cellular functions [1,2]. Effectors have diverse activities and targets, and typically have an N-terminal secretion domain and one or more C-terminal functional domains [3,4]. This review focuses on a specific family of T3SS effectors with glycosyltransferase activity that are found in Salmonella enterica and in attaching/effacing (A/E) pathogens. The T3SS1 translocates effectors across the host cell plasma membrane that promote Salmonella invasionMiicnrotoorgaenpisimtsh2e02li0a, 8l, c35e7lls in the intestine and stimulate localized inflammation [11]. Genes are colored according to their functional categories [22,28]

Glycosyltransferases
Glycosylation in Bacterial Pathogenesis
Glycosylation of Adhesins
Glycosylation of Flagellins
Modification of Host Cell Targets by Bacterial GTs
Enzymatic Activity and Structural Studies

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