Salmonella STM1697 coordinates flagella biogenesis and virulence by restricting flagellar master protein FlhD4C2 from recruiting RNA polymerase

Li, Bingqing; Yue, Yingying; Yuan, Zenglin; Zhang, Fengyu; P, Li; Song, Nannan; Lin, Wei; Liu, Yan; Yang, Yinlong; Li, Zhihui; Gu, Lichuan

doi:10.1093/nar/gkx656

Cited by 22 publications

(25 citation statements)

References 42 publications

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“…The qRT-PCR reactions were performed on a QuantStudio TM Design & Analysis Software 1.3.1 (Thermo Fisher Scientific) using SYBR Premix Ex Taq™ II Kit (TaKaRa). The expression of gapA mRNA was used to normalize the target gene expression ( 42 ). The relative transcript abundance was calculated using the 2 −ΔΔCt method ( 48 ).…”

Section: Methodsmentioning

confidence: 99%

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YdiV regulates Escherichia coli ferric uptake by manipulating the DNA-binding ability of Fur in a SlyD-dependent manner

Zhang

Dong

et al. 2020

Nucleic Acids Research

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Iron is essential for all bacteria. In most bacteria, intracellular iron homeostasis is tightly regulated by the ferric uptake regulator Fur. However, how Fur activates the iron-uptake system during iron deficiency is not fully elucidated. In this study, we found that YdiV, the flagella gene inhibitor, is involved in iron homeostasis in Escherichia coli. Iron deficiency triggers overexpression of YdiV. High levels of YdiV then transforms Fur into a novel form which does not bind DNA in a peptidyl-prolyl cis-trans isomerase SlyD dependent manner. Thus, the cooperation of YdiV, SlyD and Fur activates the gene expression of iron-uptake systems under conditions of iron deficiency. Bacterial invasion assays also demonstrated that both ydiV and slyD are necessary for the survival and growth of uropathogenic E. coli in bladder epithelial cells. This reveals a mechanism where YdiV not only represses flagella expression to make E. coli invisible to the host immune system, but it also promotes iron acquisition to help E. coli overcome host nutritional immunity.

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Section: Methodsmentioning

confidence: 99%

“…This negatively regulates flagella biogenesis and, thus, bacterial motility ( 38–40 ). Interestingly, YdiV is induced under nutrient-starvation conditions ( 41 ), and its homologue is highly upregulated during invasion of Salmonella ( 42 ), which suggests its important role in bacterial infection.…”

Section: Introductionmentioning

confidence: 99%

YdiV regulates Escherichia coli ferric uptake by manipulating the DNA-binding ability of Fur in a SlyD-dependent manner

Zhang

Dong

et al. 2020

Nucleic Acids Research

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“…Proteins were purified by Ni 2+ -NTA affinity column. The His-tag of the proteins was removed by PPase treatment 48 . Then proteins were then concentrated and purified by Superdex 200 chromatography.…”

Section: Protein Expression and Purificationmentioning

confidence: 99%

The YdiU Domain Modulates Bacterial Stress Signaling through Mn²⁺-dependent UMPylation

Yang

Yue

Song

et al. 2019

Preprint

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SUMMARYSensing stressful conditions and adjusting cellular metabolism to adapt to the environment is essential for bacteria to survive in variable situations. Here, we describe a new stress-related protein YdiU, and characterize YdiU as an enzyme that catalyzes the covalent attachment of uridine 5’-monophosphate to a protein tyrosine/histidine residue—a novel modification defined as UMPylation. Mn2+ serves as an essential co-factor for YdiU-mediated UMPylation. UTP and Mn2+-binding converts YdiU to an aggregate-prone state facilitating the recruitment of chaperones. The UMPylation of chaperones prevents them from binding co-factors or clients, thereby impairing their function. Consistent with the recent finding that YdiU acts as an AMPylator, we further demonstrate that the self-AMPylation of YdiU padlocks its chaperone-UMPylation activity. The detailed mechanism is proposed based on Apo-YdiU, YdiU-ATP, YdiU-AMP crystal structures and molecular dynamics simulation models of YdiU-UTP and YdiU-UTP-peptide. In vivo data demonstrate that YdiU effectively protects Salmonella from stress-induced ATP depletion through UMPylation.HighlightsYdiU involves in stress-resistance of Salmonella.YdiU mediates protein UMPylation in a Mn2+-dependent manner.Structural insights into YdiU-mediated UMPylation.UMPylation of chaperones by YdiU modulates their function.

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“…The transcriptome and proteome landscape of intracellular S. Typhimurium has revealed that the expression of most flagellar genes is significantly downregulated after the entry of S. Typhimurium into murine macrophages [22][23][24]. The deletion of STM1697, which encodes an EAL-like protein, resulted in the upregulation of flagellar gene expression, leading to the attenuated ability of S. Typhimurium to colonize the host organs [25]. These results implicate that the downregulation of flagellar genes in macrophages contributes to the successful intracellular replication and full virulence of S. Typhimurium.…”

Section: Introductionmentioning

confidence: 99%

Downregulation of a novel flagellar synthesis regulator AsiR promotes intracellular replication and systemic pathogenicity of Salmonella Typhimurium

Jiang

Wang

et al. 2021

Virulence

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The intracellular pathogen Salmonella enterica serovar Typhimurium ( S . Typhimurium) exploits host macrophage as a crucial survival and replicative niche. To minimize host immune response stimulated by flagellin, the expression of flagellar genes is downregulated during S . Typhimurium growth within host macrophages. However, the underlying mechanisms are largely unknown. In this study, we show that STM14_1285 (named AsiR), a putative RpiR-family transcriptional regulator, which is downregulated within macrophages as previously reported and also confirmed here, positively regulates the expression of flagellar genes by directly binding to the promoter of flhDC . By generating an asiR mutant strain and a strain that persistently expresses asiR gene within macrophages, we confirmed that the downregulation of asiR contributes positively to S . Typhimurium replication in macrophages and systemic infection in mice, which could be attributed to decreased flagellar gene expression and therefore reduced flagellin-stimulated secretion of pro-inflammatory cytokines IL-1β and TNF-α. Furthermore, the acidic pH in macrophages is identified as a signal for the downregulation of asiR and therefore flagellar genes. Collectively, our results reveal a novel acidic pH signal-mediated regulatory pathway that is utilized by S . Typhimurium to promote intracellular replication and systemic pathogenesis by repressing flagellar gene expression.

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Salmonella STM1697 coordinates flagella biogenesis and virulence by restricting flagellar master protein FlhD4C2 from recruiting RNA polymerase

Cited by 22 publications

References 42 publications

YdiV regulates Escherichia coli ferric uptake by manipulating the DNA-binding ability of Fur in a SlyD-dependent manner

YdiV regulates Escherichia coli ferric uptake by manipulating the DNA-binding ability of Fur in a SlyD-dependent manner

The YdiU Domain Modulates Bacterial Stress Signaling through Mn²⁺-dependent UMPylation

Downregulation of a novel flagellar synthesis regulator AsiR promotes intracellular replication and systemic pathogenicity of Salmonella Typhimurium

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Salmonella STM1697 coordinates flagella biogenesis and virulence by restricting flagellar master protein FlhD4C2 from recruiting RNA polymerase

Cited by 22 publications

References 42 publications

YdiV regulates Escherichia coli ferric uptake by manipulating the DNA-binding ability of Fur in a SlyD-dependent manner

YdiV regulates Escherichia coli ferric uptake by manipulating the DNA-binding ability of Fur in a SlyD-dependent manner

The YdiU Domain Modulates Bacterial Stress Signaling through Mn2+-dependent UMPylation

Downregulation of a novel flagellar synthesis regulator AsiR promotes intracellular replication and systemic pathogenicity of Salmonella Typhimurium

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The YdiU Domain Modulates Bacterial Stress Signaling through Mn²⁺-dependent UMPylation