Activity of acetyltransferase toxins involved in Salmonella persister formation during macrophage infection

Rycroft, Julian Anthony; Gollan, Bridget; Grabe, Grzegorz; Hall, A.; Cheverton, Angela M.; Larrouy-Maumus, Gérald; Hare, S.; Hélaine, Sophie

doi:10.1038/s41467-018-04472-6

Cited by 90 publications

(116 citation statements)

References 34 publications

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“…In turn, the secreted KRS could promote the production of pro-inflammatory cytokines in THP-1 cells, such as IL-8, IL-1β, and TNF-α. Differing from Shiga toxins, the acetyltransferase toxins produced by Salmonella Enteritidis and Typhimurium inhibited translation in macrophages by acetylation of aminoacyl-tRNAs, thereby inducing Salmonella persister formation during infection 107 . In conclusion, host ARSs not only participate in the HIV assembly, but also protect against bacterial and viral infections by modulating the immune responses, indicating that ARSs play an important role in infectious diseases.…”

Section: Arss In Bacterial Infectionmentioning

confidence: 99%

Roles of aminoacyl-tRNA synthetases in immune regulation and immune diseases

Nie

Sun

et al. 2019

Cell Death Dis

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Aminoacyl-tRNA synthetases (ARSs) play a vital role in protein synthesis by linking amino acids to their cognate transfer RNAs (tRNAs). This typical function has been well recognized over the past few decades. However, accumulating evidence reveals that ARSs are involved in a wide range of physiological and pathological processes apart from translation. Strikingly, certain ARSs are closely related to different types of immune responses. In this review, we address the infection and immune responses induced by pathogen ARSs, as well as the potential anti-infective compounds that target pathogen ARSs. Meanwhile, we describe the functional mechanisms of ARSs in the development of immune cells. In addition, we focus on the roles of ARSs in certain immune diseases, such as autoimmune diseases, infectious diseases, and tumor immunity. Although our knowledge of ARSs in the immunological context is still in its infancy, research in this field may provide new ideas for the treatment of immune-related diseases.

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Section: Arss In Bacterial Infectionmentioning

confidence: 99%

Roles of aminoacyl-tRNA synthetases in immune regulation and immune diseases

Nie

Sun

et al. 2019

Cell Death Dis

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“…Next, we investigated Salmonella cells during macrophage infection. The fate of Salmonella after entering macrophages is known to be heterogeneous: some cells survive and proliferate, whereas others lyse in the harsh intracellular environment [30–32]. Previous studies have suggested that variations in Salmonella cell wall structure may play an important role in heterogeneous infection outcomes [33], but it has been challenging to measure such phenotypic variations in situ .…”

Section: Resultsmentioning

confidence: 99%

Mechanically Resolved Imaging of Bacteria using Expansion Microscopy

Lim

Khariton

Lane

et al. 2019

Preprint

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18Imaging dense and diverse microbial communities has broad applications in basic microbiology 19 and medicine, but remains a grand challenge due to the fact that many species adopt similar 20 morphologies. While prior studies have relied on techniques involving spectral labeling, we have 21 developed an expansion microscopy method (µExM) in which cells are physically expanded 22 prior imaging and their expansion patterns depend on the structural and mechanical properties of 23 their cell walls, which vary across species and conditions. We use this phenomenon as a 24 quantitative and sensitive phenotypic imaging contrast orthogonal to spectral separation in order 25 to resolve bacterial cells of different species or in distinct physiological states. Focusing on host- 26 microbe interactions that are difficult to quantify through fluorescence alone, we demonstrate the 27 ability of µExM to distinguish species within a dense community through in vivo imaging of a 28 model gut microbiota, and to sensitively detect cell-envelope damage caused by antibiotics or 29 previously unrecognized cell-to-cell phenotypic heterogeneity among pathogenic bacteria as they 30 infect macrophages. 32Imaging of heterogeneous bacterial populations has broad applications in understanding the 33 complex microbiota that exist on and within our bodies, as well as complex host-microbial 34 interfaces, yet remains a significant challenge due to the lack of suitable tools for distinguishing 35 species and identifying altered physiological states [1][2][3]. Analyses to date have mostly relied on 36 spectral separation using fluorescence in situ hybridization (FISH) with probes designed to target 37 16S RNA sequences specific to certain taxa [4], or genetically engineered microbes that express 38 distinct fluorescent proteins [5]. However, these methods are generally insensitive to 39 physiological changes in bacterial cells that are often modulated by host environments and 40 believed to be critical for the growth and spatial organizations of microbes [6,7]. 42The bacterial cell wall is a macromolecule responsible for shape determination in virtually all 43 bacteria. Although little is known about the molecular architecture of the cell wall in most non-44 model organisms, its dimensions can vary widely, with the wall typically thick (tens of 45 nanometers [8,9]) in Gram-positive species and thin (~2-4 nm) in Gram-negative species [10], 46 and their rigidity can vary across ~10-100 MPa for Young's modulus [11,12]. The cell wall also 47 has various biochemical compositions [13] and exhibit distinct spatial patterns of cross-linking 48 density [14], molecular organization [15,16], thickness [8,9], and stiffness [11,12], all of which 49 depend on species and cell physiology. Thus, cell wall mechanics can potentially provide a 50 contrast that is orthogonal to spectral separation in distinguishing species and even cellular 51 physiological states. However, while cell-wall structure and mechanics have been measured by 52 e...

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“…It is worth noting that more than 100 autoimmune or chronic inflammatory human diseases affect 5%-10% of the population worldwide. 8 Moreover, defects in the enzymes that catalysed tRNA modification and aminoacylation contributed to the abnormalities in the immune system. 2,3 Transfer RNAs (tRNAs), traditionally considered as adaptor molecules, can translate messenger RNAs (mRNAs) into proteins by delivering various amino acids.…”

Section: Introductionmentioning

confidence: 99%

“…7 Acetyltransferase toxins secreted by Salmonella suppressed protein translation by acetylation of aminoacyl-tRNAs and thus induced the persister state in human macrophages. 8 Moreover, defects in the enzymes that catalysed tRNA modification and aminoacylation contributed to the abnormalities in the immune system. 9,10 Therefore, the study of tRNAs in the setting of immunity has proven particularly meaningful.…”

Section: Introductionmentioning

confidence: 99%

The tRNA‐associated dysregulation in immune responses and immune diseases

et al. 2019

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Transfer RNA (tRNA), often considered as a housekeeping molecule, mainly participates in protein translation by transporting amino acids to the ribosome. Nevertheless, accumulating evidence has shown that tRNAs are closely related to various physiological and pathological processes. The proper functioning of the immune system is the key to human health. The aim of this review is to investigate the relationships between tRNAs and the immune system. We detail the biogenesis and structure of tRNAs and summarize the pathogen tRNA-mediated infection and host responses. In addition, we address recent advances in different aspects of tRNA-associated dysregulation in immune responses and immune diseases, such as tRNA molecules, tRNA modifications, tRNA derivatives and tRNA aminoacylation. Therefore, tRNAs play an important role in immune regulation. Although our knowledge of tRNAs in the context of immunity remains, for the most part, unknown, this field deserves in-depth research to provide new ideas for the treatment of immune diseases. K E Y W O R D Sbiogenesis, immune diseases, immune responses, tRNA F I G U R E 1 The biogenesis and structure of tRNAs. tRNA: Transfer RNA; Pol III: RNA polymerase III; pre-tRNA: Precursor tRNA; mRNA: Messenger RNA; aaRS: Aminoacyl-tRNA synthetase; tsRNA: tRNA-derived small RNA; tRF: tRNA-derived fragment; tiRNA: tRNA-derived stress-induced RNA

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Activity of acetyltransferase toxins involved in Salmonella persister formation during macrophage infection

Cited by 90 publications

References 34 publications

Roles of aminoacyl-tRNA synthetases in immune regulation and immune diseases

Roles of aminoacyl-tRNA synthetases in immune regulation and immune diseases

Mechanically Resolved Imaging of Bacteria using Expansion Microscopy

The tRNA‐associated dysregulation in immune responses and immune diseases

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