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

Gao, Ting; Tan, Meifang; Liu, Wanquan; Zhāng, Téngfēi; Zheng, Linlin; Zhu, Jiawen; Li, Lü; Zhou, Rui

doi:10.3389/fcimb.2016.00044

Cited by 28 publications

(23 citation statements)

References 55 publications

(64 reference statements)

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“…Transmission electron microscopy (TEM) assays were performed in accordance with previously described methods (Gao et al., ). SC‐19, Δ msmK , and CΔ msmK were harvested at OD 600 of 0.8 and fixed with 2.5% glutaraldehyde overnight.…”

Section: Methodsmentioning

confidence: 99%

The involvement of MsmK in pathogenesis of the Streptococcus suis serotype 2

et al. 2017

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Streptococcus suis serotype 2 (SS2) is an important swine and human pathogen that causes global economic and public health problems. Virulent S. suis strains successfully maintain high bacterial concentrations in host blood and rapidly adapt to challenging environments within hosts. Successful survival in hosts is a major factor influencing the pathogenesis of SS2. We have previously identified that SS2 colonization in mouse brain is possibly affected by the ATPase, MsmK of carbohydrate ATP‐binding cassette (ABC) transporters because of carbohydrate utilization. In this study, the chain length of the msmK deletion mutant was longer than that of the wild type, and the former was significantly more susceptible than the latter when theses strains were exposed to mouse blood both in vivo and in vitro. The hemolytic activity of the mutant strain was decreased. Although the adhesion of the mutant to HEp‐2 cell lines was enhanced, the deletion of msmK impaired the abilities of SS2 to resist phagocytosis and survive severe stress conditions. MsmK contributed to the survival and adaptation of SS2 in host bloodstream. Therefore, MsmK was identified as a multifunctional component that not only contributed to carbohydrate utilization but also participated in SS2 pathogenesis.

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Section: Methodsmentioning

confidence: 99%

The involvement of MsmK in pathogenesis of the Streptococcus suis serotype 2

et al. 2017

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“…Mutations in the tRNA modification enzyme MnmG/GidA also influence bacterial virulence, presumably because they increase the frequency of a two-base frameshift during translation of mRNA ( Shippy and Fadl, 2015 ; Gao et al, 2016 ). This led to suggestions that a gidA deletion could be used as an attenuated vaccine candidate ( Shippy and Fadl, 2012 ).…”

Section: Mutations In Folate- and Flavin-dependent Methyltransferasesmentioning

confidence: 99%

Unique Features and Anti-microbial Targeting of Folate- and Flavin-Dependent Methyltransferases Required for Accurate Maintenance of Genetic Information

et al. 2018

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Comparative genome analyses have led to the discovery and characterization of novel flavin- and folate-dependent methyltransferases that mainly function in DNA precursor synthesis and post-transcriptional RNA modification by forming (ribo) thymidylate and its derivatives. Here we discuss the recent literature on the novel mechanistic features of these enzymes sometimes referred to as “uracil methyltransferases,” albeit we prefer to refer to them as (ribo) thymidylate synthases. These enzyme families attest to the convergent evolution of nucleic acid methylation. Special focus is given to describing the unique characteristics of these flavin- and folate-dependent enzymes that have emerged as new models for studying the non-canonical roles of reduced flavin co-factors (FADH2) in relaying carbon atoms between enzyme substrates. This ancient enzymatic methylation mechanism with a very wide phylogenetic distribution may be more commonly used for biological methylation reactions than previously anticipated. This notion is exemplified by the recent discovery of additional substrates for these enzymes. Moreover, similar reaction mechanisms can be reversed by demethylases, which remove methyl groups e.g., from human histones. Future work is now required to address whether the use of different methyl donors facilitates the regulation of distinct methylation reactions in the cell. It will also be of great interest to address whether the low activity flavin-dependent thymidylate synthases ThyX represent ancestral enzymes that were eventually replaced by the more active thymidylate synthases of the ThyA family to facilitate the maintenance of larger genomes in fast-growing microbes. Moreover, we discuss the recent efforts from several laboratories to identify selective anti-microbial compounds that target flavin-dependent thymidylate synthase ThyX. Altogether we underline how the discovery of the alternative flavoproteins required for methylation of DNA and/or RNA nucleotides, in addition to providing novel targets for antibiotics, has provided new insight into microbial physiology and virulence.

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“…Transmission electron microscopy assays were performed in accordance with previously described methods with minor modifications [ 25 ]. WT, mutation, and complementation strains were harvested at an OD600 of 0.6 and fixed with 2.5% glutaraldehyde overnight.…”

Section: Methodsmentioning

confidence: 99%

Screening of Virulence-Related Transcriptional Regulators in Streptococcus suis

Liu

Zhang

et al. 2020

Genes

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Streptococcus suis (S.suis) is an important zoonotic pathogen that causes many severe diseases in pigs and humans. Virulence-related transcriptional regulators have been widely reported in pathogenic microorganisms, but only a few have been identified in S.suis. Our aim was to screen virulence-related transcriptional regulators in S.suis. A total of 89 such genes were predicted in the S.suis genome, of which 22 were up-regulated and 18 were down-regulated during S.suis infection in mice. To evaluate the roles of these differentially expressed factors in S.suis virulence, deletion mutants were constructed, and 10 mutants were successfully obtained. Among these genes, the deletion of comR, sitR, or sxvR caused significantly decreased virulence in mice, compared to that with the wild-type strain. Moreover, the survival of ΔcomR, ΔsitR, and ΔsxvR mutant strains in blood was significantly reduced both in vitro and in vivo. Furthermore, their pro-inflammatory abilities were also obviously decreased in vivo. The regulatory mechanisms of comR, sitR, and sxvR were then analyzed by whole transcriptome RNA sequencing (RNA-Seq). Results indicated that the absence of comR induced the down-regulation of 17 virulence factors or virulence-related factors, including genes involved in the synthesis of capsules, oxidative stress tolerance, immune evasion, and cell division. Furthermore, three and two virulence factors or virulence-related factors were down-regulated upon deletion of sitR and sxvR, respectively. Thus, this study reports the discovery of three virulence-associated transcriptional regulatory factors in S.suis. These factors could ultimately be targeted to control infection caused by these bacteria.

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

Cited by 28 publications

References 55 publications

The involvement of MsmK in pathogenesis of the Streptococcus suis serotype 2

The involvement of MsmK in pathogenesis of the Streptococcus suis serotype 2

Unique Features and Anti-microbial Targeting of Folate- and Flavin-Dependent Methyltransferases Required for Accurate Maintenance of Genetic Information

Screening of Virulence-Related Transcriptional Regulators in Streptococcus suis

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