ADP-ribosylation systems in bacteria and viruses

Mikolčević, Petra; Hloušek-Kasun, Andrea; Ahel, Ivan; Mikoč, Andreja

doi:10.1016/j.csbj.2021.04.023

Cited by 41 publications

(49 citation statements)

References 193 publications

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“…The wide distribution of the arr gene in environmental bacteria and the apparent plasticity of Arr interactions suggest that it may be able to act on substrates other than rifamycins 1 , 5 , 9 . Genomic analyses considering the different arr genetic neighborhoods revealed some common elements close to the arr gene, such as ncRNA genes (e.g., AAC_AAD_leader, RNaseP_bact_a, and ykkC-III).…”

Section: Discussionmentioning

confidence: 99%

“…Arr is a small enzyme (16 kDa) with low sequence similarity to other known ARTs, however, shares structural homology with them. The arr gene was firstly described in Mycolicibacterium smegmatis ( arr -ms or arr -1) 3 , and since then other alleles have been identified in some organisms of Actinobacteria , Proteobacteria , and Firmicutes phyla, in addition to marine and soil microbiomes 1 , 2 , 4 , 5 . However, Arr current distribution and prevalence in the Bacteria domain is unknown.…”

Section: Introductionmentioning

confidence: 99%

“…Besides these Arr enzymes, few others (Arr-3 to Arr-8, Arr-cb, Arr-sc, Arr_Mab) have already been characterized 2 , 4 , 6 – 8 . Although Arr has been associated primarily with resistance to clinically important rifamycin antibiotics, some authors suggested that it may be able to act on other substrates and metabolic pathways 1 , 5 , 9 .…”

Section: Introductionmentioning

confidence: 99%

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Genomic epidemiology of rifampicin ADP-ribosyltransferase (Arr) in the Bacteria domain

Morgado

Fonseca

Vicente

2021

Sci Rep

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Arr is an ADP-ribosyltransferase enzyme primarily reported in association with rifamycin resistance, which has been used to treat tuberculosis in addition to Gram-positive infections and, recently, pan-resistant Gram-negative bacteria. The arr gene was initially identified on the Mycolicibacterium smegmatis chromosome and later on Proteobacteria plasmids. This scenario raised concerns on the distribution and spread of arr, considering the Bacteria domain. Based on 198,082 bacterial genomes/metagenomes, we performed in silico analysis, including phylogenetic reconstruction of Arr in different genomic contexts. Besides, new arr alleles were evaluated by in vitro analysis to assess their association with rifampin resistance phenotype. The arr gene was prevalent in thousands of chromosomes and in hundreds of plasmids from environmental and clinical bacteria, mainly from the phyla Actinobacteria, Proteobacteria, Firmicutes, and Bacteroidetes. Furthermore, this gene was identified in other and new genomic contexts. Interestingly, Arr sequences associated with rifampin resistance were distributed across all phylogeny, indicating that, despite the diversity, their association with rifampin resistance phenotype were maintained. In fact, we found that the key residues were highly conserved. In addition, other analyzes have raised evidence of another Arr function, which is related to guanidine metabolism. Finally, this scenario as a whole also suggested the Actinobacteria phylum as a potential ancestral source of arr within the Bacteria domain.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Genomic epidemiology of rifampicin ADP-ribosyltransferase (Arr) in the Bacteria domain

Morgado

Fonseca

Vicente

2021

Sci Rep

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“…Indeed, several ARTD family members are found to restrict viral replication 73 . On the other hand, viruses encode both ARTs as well as ADP-ribosylhydrolases 193 . For example, viral macrodomains have been described to interfere with the innate immune response 193 .…”

Section: Concluding Remarks and Perspectivesmentioning

confidence: 99%

“…On the other hand, viruses encode both ARTs as well as ADP-ribosylhydrolases 193 . For example, viral macrodomains have been described to interfere with the innate immune response 193 . This provides evidence for an ancient and central role of ADP-ribosylation in host-pathogen interactions and suggests a co-evolution of ARTs.…”

Section: Concluding Remarks and Perspectivesmentioning

confidence: 99%

Interplay between ADP-ribosyltransferases and essential cell signaling pathways controls cellular responses

2021

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Signaling cascades provide integrative and interactive frameworks that allow the cell to respond to signals from its environment and/or from within the cell itself. The dynamic regulation of mammalian cell signaling pathways is often modulated by cascades of protein post-translational modifications (PTMs). ADP-ribosylation is a PTM that is catalyzed by ADP-ribosyltransferases and manifests as mono- (MARylation) or poly- (PARylation) ADP-ribosylation depending on the addition of one or multiple ADP-ribose units to protein substrates. ADP-ribosylation has recently emerged as an important cell regulator that impacts a plethora of cellular processes, including many intracellular signaling events. Here, we provide an overview of the interplay between the intracellular diphtheria toxin-like ADP-ribosyltransferase (ARTD) family members and five selected signaling pathways (including NF-κB, JAK/STAT, Wnt-β-catenin, MAPK, PI3K/AKT), which are frequently described to control or to be controlled by ADP-ribosyltransferases and how these interactions impact the cellular responses.

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Legionella pneumophila temporally regulates the activity of ADP/ATP translocases by reversible ADP‐ribosylation

Guan

et al. 2022

mLife

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The mitochondrion is an important signaling hub that governs diverse cellular functions, including metabolism, energy production, and immunity. Among the hundreds of effectors translocated into host cells by the Dot/Icm system of Legionella pneumophila, several are targeted to mitochondria but the function of most of them remains elusive. Our recent study found that the effector Ceg3 inhibits the activity of ADP/ATP translocases (ANTs) by ADP‐ribosylation (ADPR). Here, we show that the effect of Ceg3 is antagonized by Larg1, an effector encoded by lpg0081, a gene that is situated next to ceg3. Larg1 functions to reverse Ceg3‐mediated ADPR of ANTs by cleaving the N‐glycosidic bond between the ADPR moiety and the modified arginine residues in ANTs, leading to restoration of their activity in ADP/ATP exchange. Structural analysis of Larg1 and its complex with ADPR reveals that this ADPR glycohydrolase harbors a unique macrodomain that catalyzes the removal of ADPR modification on ANTs. Our results also demonstrate that together with Ceg3, Larg1 imposes temporal regulation of the activity of ANTs by reversible ADPR during L. pneumophila infection.

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ADP-ribosylation systems in bacteria and viruses

Cited by 41 publications

References 193 publications

Genomic epidemiology of rifampicin ADP-ribosyltransferase (Arr) in the Bacteria domain

Genomic epidemiology of rifampicin ADP-ribosyltransferase (Arr) in the Bacteria domain

Interplay between ADP-ribosyltransferases and essential cell signaling pathways controls cellular responses

Legionella pneumophila temporally regulates the activity of ADP/ATP translocases by reversible ADP‐ribosylation

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