GidA, a tRNA Modification Enzyme, Contributes to the Growth, and Virulence of Streptococcus suis Serotype 2

Ting Gao,Wanquan Liu,Chunyan Zhang,Meifang Tan,Lu Li,Tengfei Zhang,Rui Zhou,Jiawen Zhu,Linlin Zheng

doi:10.3389/fcimb.2016.00044

Abstract

Glucose-inhibited division protein (GidA), is a tRNA modification enzyme functioning together with MnmE in the addition of a carboxymethylaminomethyl group to position 5 of the anticodon wobble uridine of tRNA. Here, we report a GidA homolog from a Chinese isolate SC-19 of the zoonotic Streptococcus suis serotype 2 (SS2). gidA disruption led to a defective growth, increased capsule thickness, and reduced hemolytic activity. Moreover, the gidA deletion mutant (ΔgidA) displayed reduced mortality and bacterial loads in mice, reduced ability of adhesion to and invasion in epithelial cells, and increased sensitivity to phagocytosis. The iTRAQ analysis identified 372 differentially expressed (182 up- and 190 down-regulated) proteins in ΔgidA and SC-19. Numerous DNA replication, cell division, and virulence associated proteins were downregulated, whereas many capsule synthesis enzymes were upregulated by gidA disruption. This is consistent with the phenotypes of the mutant. Thus, GidA is a translational regulator that plays an important role in the growth, cell division, capsule biosynthesis, and virulence of SS2. Our findings provide new insight into the regulatory function of GidA in bacterial pathogens.

Highlights

Streptococcus suis is an important zoonotic pathogen causing lethal infections in humans and pigs (Lun et al, 2007)
Among the 33 serotypes classified on the basis of antigenicity of capsular polysaccharide (CPS), S. suis serotype 2 (SS2) is the most virulent and prevalent strain isolated from diseased pigs (Smith et al, 1999)
GidA protein plays a different role in many bacteria: in Escherichia coli, deletion of gidA affects cell division when it is grown on glucose (Von Meyenburg et al, 1982); in Streptococcus mutans, gidA is involved in survival under stress conditions (Li et al, 2014); in Aeromonas hydrophila, gidA regulates virulence protein, cytotoxic enterotoxin (Sha et al, 2004); in Salmonella enterica, disruption of gidA affects cell division and regulates the virulence proteins (Shippy et al, 2012; Rehl et al, 2013); and in Pseudomonas syringae, gidA is a global regulator (Kinscherf and Willis, 2002)

Summary

Introduction

Streptococcus suis is an important zoonotic pathogen causing lethal infections in humans and pigs (Lun et al, 2007). S. suis primarily colonizes the palatine tonsils, which is one of its natural habitats, breaches epithelial cell barriers, reaches the bloodstream, disseminates through the blood circulation system, and invades different organs of the host (Fittipaldi et al, 2012) In this process, many proteins are regulated (up-regulated or down-regulated) at the translation level in response to surroundings change and environmental signals. GidA is a FAD-binding protein and, together with MnmE, catalyzes the addition of carboxymethylaminomethyl group at position 5 of the wobble uridine of tRNAs (Shi et al, 2009) This modification contributes to proper and efficient protein translation (Fislage et al, 2014). GidA can regulate the expression of multiple proteins at the level of translation through tRNA modification (Kinscherf and Willis, 2002; Yim et al, 2006), and can regulate the survival of bacteria under stress condition in response to environmental signals

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