AbiEi Binds Cooperatively to the Type IV abiE Toxin–Antitoxin Operator Via a Positively-Charged Surface and Causes DNA Bending and Negative Autoregulation

Hampton, Hannah G; Jackson, Simon A.; Fagerlund, Robert D.; Vogel, Anne Ilse Maria; Dy, Ron L.; Blower, Tim R.; Fineran, Peter C.

doi:10.1016/j.jmb.2018.02.022

Cited by 24 publications

(45 citation statements)

References 55 publications

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“…The other region contained genes encoding a type IV toxin-antitoxin 'innate immunity' bacterial abortive infection (Abi) system, consisted of a bicistronic operon encoding an AbiEi antitoxin and an AbiEii toxin (OG_1985 and OG_1986, Figure 7C). The Abi system, abbreviated for the phage abotive infection system, provides a post-infection resistance mechanism that could block phage multiplication and result in the death of the infected bacterial cell upon phage infection [81][82][83], and also might act as stress-response elements that help cells survive unfavorable growth conditions [84]. Beside these two genomic regions, there were also two genes (OG_1915 and OG_2057) showing a signi cant association with NHA habitat.…”

Section: High Level Of Homologous Recombination In M Luteus Speciesmentioning

confidence: 99%

Comparative Genomics Reveals Broad Genetic Diversity, Extensive Recombination and Nascent Ecological Adaptation in Micrococcus luteus

Sun

Rong

et al. 2020

Preprint

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Background: Micrococcus luteus is a group of actinobacteria that is widely used in biotechnology and is being thought as an emerging nosocomial pathogen. With one of the smallest genomes of free-living actinobacteria, it is found in a wide range of environments, but intraspecies genetic diversity and adaptation strategies to various environments remain unclear. Here, comparative genomics, phylogenomics, and genome-wide association studies (GWAS) were used to investigate the genomic diversity, evolutionary history, and the potential ecological differentiation of the species.Results: High-quality genomes of 66 M. luteus strains were downloaded from the NCBI GenBank database and core and pangenome analysis revealed a considerable intraspecies heterogeneity. Phylogenomic analysis, gene content comparison, and average nucleotide identity calculation consistently indicated that the species has diverged into three well-differentiated clades. Population structure analysis revealed four admixed ancestral subpopulations, with three of them corresponding to the three clades, respectively, and the fourth corresponding to an unknown ancestor or the fourth, yet unsampled, clade. Reconstruction of gene gain/loss events along the evolutionary history revealed both early events that contributed to the inter-clade divergence and recent events leading to the intra-clade diversity. We also found convincing evidence that recombination has played a key role of the evolutionary process of the species, with upto two-thirds of the core genes have been affected by recombination. Furthermore, distribution of mammal-associated strains (including pathogens) on the phylogenetic tree strongly suggested that the last common ancestor had a free-living lifestyle, and a few recently diverged lineages have developed a mammal-associated lifestyle separately. Consistently, genome-wide association studies revealed that mammal-associated strains from different lineages shared genes functionally relevant to the host-associated lifestyle, indicating a recent ecological adaption to the new host-associated habitats.Conclusions: These results revealed high intraspecies genomic diversity of M. luteus and highlighted that gene gain/loss events and extensive recombination events played key roles in the genome evolution. Our study also indicated that, as a free-living species, some lineages have recently developed or are developing a mammal-associated lifestyle. This study provides insights into the mechanisms that drive the genome evolution and adaption to various environments of a bacterial species.

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Section: High Level Of Homologous Recombination In M Luteus Speciesmentioning

confidence: 99%

Comparative Genomics Reveals Broad Genetic Diversity, Extensive Recombination and Nascent Ecological Adaptation in Micrococcus luteus

Sun

Rong

et al. 2020

Preprint

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“…We present the solved structure of S. agalactiae AbiEi, demonstrating structural homology between the COG5340 antitoxins, and biochemically characterize the molecular interactions underpinning transcriptional repression by Rv2827c. Interestingly, this is a more complex autoregulatory system than previously seen for AbiEi [29].…”

Section: Introductionmentioning

confidence: 65%

“…Autoregulation of TA system expression is a hallmark of type II TA systems and can be either positive or negative [27,28]. The antitoxin AbiEi from S. agalactiae has been biochemically characterized [15,29] and functions as both an antitoxin and a transcriptional repressor. That is, AbiEi negatively autoregulates abiE expression.…”

Section: Introductionmentioning

confidence: 99%

“…Full length AbiEi is required for negative autoregulation and induced bending of the promoter DNA. We previously proposed that this bending was facilitated by the two AbiEi monomers interacting via their C-terminal domains (CTDs) [29]. In contrast with type II autoregulation, for which conditional co-operativity is observed, co-expression of the cognate toxin AbiEii does not enhance transcriptional repression [15].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Antitoxin autoregulation of M. tuberculosis toxin-antitoxin expression through negative cooperativity arising from multiple inverted repeat sequences

Beck

Usher

Hampton

et al. 2020

Biochemical Journal

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Toxin-antitoxin systems play key roles in bacterial adaptation, including protection from antibiotic assault and infection by bacteriophages. The type IV toxin-antitoxin system AbiE encodes a DUF1814 nucleotidyltransferase-like toxin, and a two-domain antitoxin. In Streptococcus agalactiae, the antitoxin AbiEi negatively autoregulates abiE expression through positively co-operative binding to inverted repeats within the promoter. The human pathogen Mycobacterium tuberculosis encodes four DUF1814 putative toxins, two of which have antitoxins homologous to AbiEi. One such M. tuberculosis antitoxin, named Rv2827c, is required for growth and whilst the structure has previously been solved, the mode of regulation is unknown. To complete the gaps in our understanding, we first solved the structure of S. agalactiae AbiEi to 1.83 Å resolution for comparison with M. tuberculosis Rv2827c. AbiEi contains an N-terminal DNA binding domain and C-terminal antitoxicity domain, with bilateral faces of opposing charge. The overall AbiEi fold is similar to Rv2827c, though smaller, and with a 65° difference in C-terminal domain orientation. We further demonstrate that, like AbiEi, Rv2827c can autoregulate toxin-antitoxin operon expression. In contrast with AbiEi, the Prv2827c promoter contains two sets of inverted repeats, which bind Rv2827c with differing affinities depending on the sequence consensus. Surprisingly, Rv2827c bound with negative co-operativity to the full Prv2827c promoter, demonstrating an unexpectedly complex form of transcriptional regulation.

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“…A TA pair composed of a toxin harboring the GNAT domain (GCN5-related Nacetyltransferases, originally derived from GCN5 (general control non-repressible 5), a histone acetyltransferase [31]), and an antitoxin harboring the HTH (Helix-Turn-Helix) domain or its variants, RHH (Ribbon-Helix-Helix) [32] or wHTH (winged Helix-Turn-Helix) belongs to type II TA families [22,[33][34][35][36].…”

Section: Gnat-hth (Gacta)mentioning

confidence: 99%

Towards Exploring Toxin-Antitoxin Systems in <em>Geobacillus</em>: A Screen for Type II Toxin-Antitoxin System Families in A Thermophilic Genus

Alkhalili

Wallenius

Canbäck

2019

Preprint

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The toxin-antitoxin (TA) systems have been attracting attention due to their role in regulating prokaryotic cell responses to stress and their biotechnological potential. Much recognition has been given to type II TA system of mesophiles, but so far, limited attention has been given to thermophiles. Here, we are presenting the putative type II TA families encoded on the genomes of four Geobacillus strains. We employed the TA finder tool to mine for TA-coding genes and manually curated the results using various tools. We identified 28 putative TA pairs, distributed over 8 TA families. Among the identified TAs, 15 represent putative novel toxins and antitoxins that have been overlooked or annotated as hypothetical proteins in their genome records. We also identified a potentially new TA composite, AbrB-ParE. Furthermore, we are suggesting the Geobacillus acetyltransferase toxin-antitoxin (GacTA) family which potentially represents one of the unique TA families that has a reverse gene order. Moreover, we are proposing a hypothesis on the regulation of the xre-cog2856 gene expression, which seems to involve c-di-AMP. This study aims for highlighting the significance of studying TAs in Geobacillus, since they have special features. It also aims for facilitating future experimental research.

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AbiEi Binds Cooperatively to the Type IV abiE Toxin–Antitoxin Operator Via a Positively-Charged Surface and Causes DNA Bending and Negative Autoregulation

Cited by 24 publications

References 55 publications

Comparative Genomics Reveals Broad Genetic Diversity, Extensive Recombination and Nascent Ecological Adaptation in Micrococcus luteus

Comparative Genomics Reveals Broad Genetic Diversity, Extensive Recombination and Nascent Ecological Adaptation in Micrococcus luteus

Antitoxin autoregulation of M. tuberculosis toxin-antitoxin expression through negative cooperativity arising from multiple inverted repeat sequences

Towards Exploring Toxin-Antitoxin Systems in <em>Geobacillus</em>: A Screen for Type II Toxin-Antitoxin System Families in A Thermophilic Genus

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