Diverse genetic contexts of HicA toxin domains propose a role in anti-phage defense
ABSTRACT Toxin–antitoxin (TA) modules are prevalent in prokaryotic genomes, often in substantial numbers. For instance, the Mycobacterium tuberculosis genome alone harbors close to 100 TA modules, half of which belong to a singular type. Traditionally ascribed multiple biological roles, recent insig...
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2024-02-01
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| Series: | mBio |
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| Online Access: | https://journals.asm.org/doi/10.1128/mbio.03293-23 |
| _version_ | 1827150289250025472 |
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| author | Kenn Gerdes |
| author_facet | Kenn Gerdes |
| author_sort | Kenn Gerdes |
| collection | DOAJ |
| description | ABSTRACT Toxin–antitoxin (TA) modules are prevalent in prokaryotic genomes, often in substantial numbers. For instance, the Mycobacterium tuberculosis genome alone harbors close to 100 TA modules, half of which belong to a singular type. Traditionally ascribed multiple biological roles, recent insights challenge these notions and instead indicate a predominant function in phage defense. TAs are often located within Defense Islands, genomic regions that encode various defense systems. The analysis of genes within Defense Islands has unveiled a wide array of systems, including TAs that serve in anti-phage defense. Prokaryotic cells are equipped with anti-phage Viperins that, analogous to their mammalian counterparts, inhibit viral RNA transcription. Additionally, bacterial Structural Maintenance of Chromosome (SMC) proteins combat plasmid intrusion by recognizing foreign DNA signatures. This study undertakes a comprehensive bioinformatics analysis of genetic elements encoding the HicA double-stranded RNA-binding domain, complemented by protein structure modeling. The HicA toxin domains are found in at least 14 distinct contexts and thus exhibit a remarkable genetic diversity. Traditional bicistronic TA operons represent eight of these contexts, while four are characterized by monocistronic operons encoding fused HicA domains. Two contexts involve hicA adjacent to genes that encode bacterial Viperins. Notably, genes encoding RelE toxins are also adjacent to Viperin genes in some instances. This configuration hints at a synergistic enhancement of Viperin-mediated anti-phage action by HicA and RelE toxins. The discovery of a HicA domain merged with an SMC domain is compelling, prompting further investigation into its potential roles.IMPORTANCEProkaryotic organisms harbor a multitude of toxin–antitoxin (TA) systems, which have long puzzled scientists as “genes in search for a function.” Recent scientific advancements have shed light on the primary role of TAs as anti-phage defense mechanisms. To gain an overview of TAs it is important to analyze their genetic contexts that can give hints on function and guide future experimental inquiries. This article describes a thorough bioinformatics examination of genes encoding the HicA toxin domain, revealing its presence in no fewer than 14 unique genetic arrangements. Some configurations notably align with anti-phage activities, underscoring potential roles in microbial immunity. These insights robustly reinforce the hypothesis that HicA toxins are integral components of the prokaryotic anti-phage defense repertoire. The elucidation of these genetic contexts not only advances our understanding of TAs but also contributes to a paradigm shift in how we perceive their functionality within the microbial world. |
| first_indexed | 2024-03-08T01:25:37Z |
| format | Article |
| id | doaj.art-2b4fcbdf2f554d1287db87cdc955bbe2 |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2025-03-20T21:31:43Z |
| publishDate | 2024-02-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-2b4fcbdf2f554d1287db87cdc955bbe22024-08-11T18:24:59ZengAmerican Society for MicrobiologymBio2150-75112024-02-0115210.1128/mbio.03293-23Diverse genetic contexts of HicA toxin domains propose a role in anti-phage defenseKenn Gerdes0Kenn Gerdes is an independent researcher with the residence, Voldmestergade, Copenhagen, DenmarkABSTRACT Toxin–antitoxin (TA) modules are prevalent in prokaryotic genomes, often in substantial numbers. For instance, the Mycobacterium tuberculosis genome alone harbors close to 100 TA modules, half of which belong to a singular type. Traditionally ascribed multiple biological roles, recent insights challenge these notions and instead indicate a predominant function in phage defense. TAs are often located within Defense Islands, genomic regions that encode various defense systems. The analysis of genes within Defense Islands has unveiled a wide array of systems, including TAs that serve in anti-phage defense. Prokaryotic cells are equipped with anti-phage Viperins that, analogous to their mammalian counterparts, inhibit viral RNA transcription. Additionally, bacterial Structural Maintenance of Chromosome (SMC) proteins combat plasmid intrusion by recognizing foreign DNA signatures. This study undertakes a comprehensive bioinformatics analysis of genetic elements encoding the HicA double-stranded RNA-binding domain, complemented by protein structure modeling. The HicA toxin domains are found in at least 14 distinct contexts and thus exhibit a remarkable genetic diversity. Traditional bicistronic TA operons represent eight of these contexts, while four are characterized by monocistronic operons encoding fused HicA domains. Two contexts involve hicA adjacent to genes that encode bacterial Viperins. Notably, genes encoding RelE toxins are also adjacent to Viperin genes in some instances. This configuration hints at a synergistic enhancement of Viperin-mediated anti-phage action by HicA and RelE toxins. The discovery of a HicA domain merged with an SMC domain is compelling, prompting further investigation into its potential roles.IMPORTANCEProkaryotic organisms harbor a multitude of toxin–antitoxin (TA) systems, which have long puzzled scientists as “genes in search for a function.” Recent scientific advancements have shed light on the primary role of TAs as anti-phage defense mechanisms. To gain an overview of TAs it is important to analyze their genetic contexts that can give hints on function and guide future experimental inquiries. This article describes a thorough bioinformatics examination of genes encoding the HicA toxin domain, revealing its presence in no fewer than 14 unique genetic arrangements. Some configurations notably align with anti-phage activities, underscoring potential roles in microbial immunity. These insights robustly reinforce the hypothesis that HicA toxins are integral components of the prokaryotic anti-phage defense repertoire. The elucidation of these genetic contexts not only advances our understanding of TAs but also contributes to a paradigm shift in how we perceive their functionality within the microbial world.https://journals.asm.org/doi/10.1128/mbio.03293-23HicAHicBtoxinRNaseantitoxinRelE |
| spellingShingle | Kenn Gerdes Diverse genetic contexts of HicA toxin domains propose a role in anti-phage defense mBio HicA HicB toxin RNase antitoxin RelE |
| title | Diverse genetic contexts of HicA toxin domains propose a role in anti-phage defense |
| title_full | Diverse genetic contexts of HicA toxin domains propose a role in anti-phage defense |
| title_fullStr | Diverse genetic contexts of HicA toxin domains propose a role in anti-phage defense |
| title_full_unstemmed | Diverse genetic contexts of HicA toxin domains propose a role in anti-phage defense |
| title_short | Diverse genetic contexts of HicA toxin domains propose a role in anti-phage defense |
| title_sort | diverse genetic contexts of hica toxin domains propose a role in anti phage defense |
| topic | HicA HicB toxin RNase antitoxin RelE |
| url | https://journals.asm.org/doi/10.1128/mbio.03293-23 |
| work_keys_str_mv | AT kenngerdes diversegeneticcontextsofhicatoxindomainsproposearoleinantiphagedefense |