Bacteria-Catalyzed Arginine Glycosylation in Pathogens and Host

Xing, Puyuan; Luo, Jie; Li, Shan

doi:10.3389/fcimb.2020.00185

Cited by 25 publications

(21 citation statements)

References 86 publications

(162 reference statements)

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“…SseK1, SseK2, and SseK3 are SPI-2 effectors that share high sequence identities with the enteropathogenic Escherichia coli T3SS effector NleB1 10,11 . Based on the knowledge of NleB1 12,13 , other groups and us report that SseK1 and SseK3 show arginine GlcNAc transferase activity and modify the death domain of tumor necrotic factor receptor-1 (TNFR1)-associated death domain protein (TRADD) and TNFR1, respectively [14][15][16] . However, a phenomenon exists whereby both the SseK3 protein and arginine-GlcNAcylated protein localize on the Golgi apparatus during Salmonella infection 17 .…”

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confidence: 99%

Arginine GlcNAcylation of Rab small GTPases by the pathogen Salmonella Typhimurium

et al. 2020

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Salmonella enterica serovar Typhimurium, an intracellular Gram-negative bacterial pathogen, employs two type III secretion systems to deliver virulence effector proteins to host cells. One such effector, SseK3, is a Golgi-targeting arginine GlcNAc transferase. Here, we show that SseK3 colocalizes with cis-Golgi via lipid binding. Arg-GlcNAc-omics profiling reveals that SseK3 modifies Rab1 and some phylogenetically related Rab GTPases. These modifications are dependent on C-termini of Rabs but independent of the GTP-or GDP-bound forms. Arginine GlcNAcylation occurs in the switch II region and the third α-helix and severely disturbs the function of Rab1. The arginine GlcNAc transferase activity of SseK3 is required for the replication of Salmonella in RAW264.7 macrophages and bacterial virulence in the mouse model of Salmonella infection. Therefore, this SseK3 mechanism of action represents a new understanding of the strategy adopted by Salmonella to target host trafficking systems.

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confidence: 99%

Arginine GlcNAcylation of Rab small GTPases by the pathogen Salmonella Typhimurium

et al. 2020

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“…The phylogenetic tree of the 12 DDs showed an evolutionary relationship based on protein sequence ( Figure 1C ). Previous studies show that the conserved arginine is critical for NleB mediated modification ( Li et al, 2013 ; Ding et al, 2019 ; Pan et al, 2020 ). Here, we screened all the arginine-containing DD proteins to be GlcNAcylated by NleB/SseKs in bacterial pathogen infection systems.…”

Section: Resultsmentioning

confidence: 99%

“…Besides that, TRADD plays roles independent of TNFR1 signaling, such as downstream of Toll-like receptors (Chen et al, 2008;Pobezinskaya et al, 2008) and DR3 (Chinnaiyan et al, 1996;Kitson et al, 1996;Pobezinskaya et al, 2011;Pobezinskaya and Liu, 2012). Type III secretion system effector NleB from enteropathogenic E. coli (EPEC) was previously reported as an arginine GlcNAc transferase that inhibited multiple death receptor mediated inflammation and cell death by modifying a conserved arginine residue in some death domain proteins (Li et al, 2013;Pearson et al, 2013;Ding et al, 2019;Pan et al, 2020;Xue et al, 2020). The arginine GlcNAc transferase activity of NleB is critical for attaching and effacing (A/E) pathogen colonization in the mouse colon (Li et al, 2013;Pearson et al, 2013;Scott et al, 2017;Ding et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

“…Intracellular pathogen Salmonella entrica strains secreted three Salmonella pathogenicity island 2 (SPI-2) effector SseK1, SseK2, and SseK3 ( Kujat Choy et al, 2004 ; Brown et al, 2011 ; Baison-Olmo et al, 2015 ; El Qaidi et al, 2017 ; Gunster et al, 2017 ; Yang et al, 2018 ; Araujo-Garrido et al, 2020 ; Meng et al, 2020 ). Crystal structure studies show that NleB, SseK1, and SseK3 belong to the GT-A family glycosyltransferase ( Esposito et al, 2018 ; Park et al, 2018 ; Ding et al, 2019 ; Araujo-Garrido et al, 2020 ; Pan et al, 2020 ). The crystal structures of NleB in complex with FADD-DD and the sugar donor, and NleB-GlcNAcylated DDs (TRADD-DD and RIPK1-DD) show that NleB is an inverting enzyme.…”

Section: Introductionmentioning

confidence: 99%

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Arg-GlcNAcylation on TRADD by NleB and SseK1 Is Crucial for Bacterial Pathogenesis

Xue

Huang

et al. 2020

Front. Cell Dev. Biol.

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Death receptor signaling is critical for cell death, inflammation, and immune homeostasis. Hijacking death receptors and their corresponding adaptors through type III secretion system (T3SS) effectors has been evolved to be a bacterial evasion strategy. NleB from enteropathogenic Escherichia coli (EPEC) and SseK1/2/3 from Salmonella enterica serovar Typhimurium (S. Typhimurium) can modify some death domain (DD) proteins through arginine-GlcNAcylation. Here, we performed a substrate screen on 12 host DD proteins with conserved arginine during EPEC and Salmonella infection. NleB from EPEC hijacked death receptor signaling through tumor necrosis factor receptor 1 (TNFR1)-associated death domain protein (TRADD), FAS-associated death domain protein (FADD), and receptor-interacting serine/threonine-protein kinase 1 (RIPK1), whereas SseK1 and SseK3 disturbed TNF signaling through the modification of TRADD Arg235/Arg245 and TNFR1 Arg376, respectively. Furthermore, mouse infection studies showed that SseK1 but not SseK3 rescued the bacterial colonization deficiency contributed by the deletion of NleBc (Citrobacter NleB), indicating that TRADD was the in vivo substrate. The result provides an insight into the mechanism by which attaching and effacing (A/E) pathogen manipulate TRADD-mediated signaling and evade host immune defense through T3SS effectors.

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“…A major theme among pathogens that have evolved to modulate cellular biology is the injection of bacterial proteins directly into the host cell through specialized nanosyringes that penetrate eukaryotic membranes and inject pathogenic effector proteins, and these nanosyringes are classified as type III-IX secretions systems [ 26 , 27 , 28 , 29 , 30 , 31 ]. Many host post-translational modifications machineries are targeted by various injected bacterial effectors [ 32 ]. Since a plethora of eukaryotic cellular processes are regulated by ubiquitination, it is not surprising that intracellular pathogens have evolved mechanisms to hijack host ubiquitination pathways to rewire host cell processes.…”

Section: Introductionmentioning

confidence: 99%

Evolution and Adaptation of Legionella pneumophila to Manipulate the Ubiquitination Machinery of Its Amoebae and Mammalian Hosts

Price

Kwaik

2021

Biomolecules

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The ubiquitin pathway is highly conserved across the eukaryotic domain of life and plays an essential role in a plethora of cellular processes. It is not surprising that many intracellular bacterial pathogens often target the essential host ubiquitin pathway. The intracellular bacterial pathogen Legionella pneumophila injects into the host cell cytosol multiple classes of classical and novel ubiquitin-modifying enzymes that modulate diverse ubiquitin-related processes in the host cell. Most of these pathogen-injected proteins, designated as effectors, mimic known E3-ubiquitin ligases through harboring F-box or U-box domains. The classical F-box effector, AnkB targets host proteins for K48-linked polyubiquitination, which leads to excessive proteasomal degradation that is required to generate adequate supplies of amino acids for metabolism of the pathogen. In contrast, the SidC and SdcA effectors share no structural similarity to known eukaryotic ligases despite having E3-ubiquitin ligase activity, suggesting that the number of E3-ligases in eukaryotes is under-represented. L. pneumophila also injects into the host many novel ubiquitin-modifying enzymes, which are the SidE family of effectors that catalyze phosphoribosyl-ubiquitination of serine residue of target proteins, independently of the canonical E1-2-3 enzymatic cascade. Interestingly, the environmental bacterium, L. pneumophila, has evolved within a diverse range of amoebal species, which serve as the natural hosts, while accidental transmission through contaminated aerosols can cause pneumonia in humans. Therefore, it is likely that the novel ubiquitin-modifying enzymes of L. pneumophila were acquired by the pathogen through interkingdom gene transfer from the diverse natural amoebal hosts. Furthermore, conservation of the ubiquitin pathway across eukaryotes has enabled these novel ubiquitin-modifying enzymes to function similarly in mammalian cells. Studies on the biological functions of these effectors are likely to reveal further novel ubiquitin biology and shed further lights on the evolution of ubiquitin.

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Bacteria-Catalyzed Arginine Glycosylation in Pathogens and Host

Cited by 25 publications

References 86 publications

Arginine GlcNAcylation of Rab small GTPases by the pathogen Salmonella Typhimurium

Arginine GlcNAcylation of Rab small GTPases by the pathogen Salmonella Typhimurium

Arg-GlcNAcylation on TRADD by NleB and SseK1 Is Crucial for Bacterial Pathogenesis

Evolution and Adaptation of Legionella pneumophila to Manipulate the Ubiquitination Machinery of Its Amoebae and Mammalian Hosts

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