RHS-elements function as type II toxin-antitoxin modules that regulate intra-macrophage replication of Salmonella Typhimurium

Stårsta, Magnus; Hammarlöf, Disa L.; Wäneskog, Marcus; Schlegel, Susan; Xu, Feifei; Gynnå, Arvid H.; Borg, Malin; Herschend, Sten; Koskiniemi, Sanna

doi:10.1371/journal.pgen.1008607

Cited by 10 publications

(8 citation statements)

References 58 publications

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“…Several previously conducted studies have indicated that bacterial toxins can be co‐opted into intracellular functions (TA systems) or as extracellular polymorphic toxins (Zhang et al, 2012; Jamet & Nassif, 2015; Triplett et al, 2016; Harms et al, 2017; Stårsta et al, 2020). The results presented here indicate that TA systems can also be converted into extracellular T6SS effectors through action of insertion elements (and possibly other kinds of genetic changes), providing novel weapons in the bacterial armory to dominate during intense competition with co‐habiting bacteria.…”

Section: Discussionmentioning

confidence: 99%

Immunity proteins of dual nuclease T6SS effectors function as transcriptional repressors

et al. 2021

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Bacteria utilize type VI secretion system (T6SS) to deliver antibacterial toxins to target co-habiting bacteria. Here, we report that Burkholderia gladioli strain NGJ1 deploys certain T6SS effectors (TseTBg), having both DNase and RNase activities to kill target bacteria. RNase activity is prominent on NGJ1 as well as other bacterial RNA while DNase activity is pertinent to only other bacteria. The associated immunity (TsiTBg) proteins harbor noncanonical helix-turn-helix motifs and demonstrate transcriptional repression activity, similar to the antitoxins of type II toxinantitoxin (TA) systems. Genome analysis reveals that homologs of TseTBg are either encoded as TA or T6SS effectors in diverse bacteria. Our results indicate that a new ORF (encoding a hypothetical protein) has evolved as a result of operonic fusion of TA type TseTBg homolog with certain T6SS-related genes by the action of IS3 transposable elements. This has potentially led to the conversion of a TA into T6SS effector in Burkholderia. Our study exemplifies that bacteria can recruit toxins of TA systems as T6SS weapons to diversify its arsenal to dominate during inter-bacterial competitions.

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Section: Discussionmentioning

confidence: 99%

Immunity proteins of dual nuclease T6SS effectors function as transcriptional repressors

et al. 2021

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“…ECL_RS07670-ECL_RS7700 genes form a putative polycistronic operon, and ECL_RS07695 codes for an Rhs toxin, which could be involved in bacteria–bacteria and bacteria–eukaryotic cell interactions, as it was reported for Dickeya dadantii and S . Typhimurium, respectively ( Koskiniemi et al, 2013 ; Starsta et al, 2020 ). Hence, DMEM components might mimic conditions that occur during the bacteria–cell host interaction and it would stimulate the transcription of ECL_RS07670-ECL_RS7700 operon in such conditions.…”

Section: Discussionmentioning

confidence: 99%

Two Type VI Secretion Systems of Enterobacter cloacae Are Required for Bacterial Competition, Cell Adherence, and Intestinal Colonization

et al. 2020

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Enterobacter cloacae has emerged as an opportunistic pathogen in healthcareassociated infections. Analysis of the genomic sequences of several E. cloacae strains revealed the presence of genes that code for expression of at least one type VI secretion system (T6SS). Here, we report that E. cloacae strain ATCC 13047 codes for two functional T6SS named T6SS-1 and T6SS-2. T6SS-1 and T6SS-2 were preferentially expressed in tryptic soy broth and tissue culture medium (DMEM), respectively. Mutants in T6SS-1-associated genes clpV1 and hcp1 significantly affected their ability of interand intra-bacterial killing indicating that T6SS-1 is required for bacterial competition. In addition, the Hcp effector protein was detected in supernatants of E. cloacae cultures and a functional T6SS-1 was required for the secretion of this protein. A clpV2 mutant was impaired in both biofilm formation and adherence to epithelial cells, supporting the notion that these phenotypes are T6SS-2 dependent. In vivo data strongly suggest that both T6SSs are required for intestinal colonization because single and double mutants in clpV1 and clpV2 genes were defective in gut colonization in mice. We conclude that the two T6SSs are involved in the pathogenesis scheme of E. cloacae with specialized functions in the interaction with other bacteria and with host cells.

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“…More importantly, deletion of the toxin genes resulted in limited intracellular survival within fibroblasts, based on survival assays, indicating the significance of the toxin genes in survival within such intracellular environments ( Lobato-Márquez et al., 2015 ). Relevance of a TA system in survival of S. Typhimurium is not new, as Type II TA modules have previously been suggested in S. Typhimurium persistence within macrophages ( Stårsta et al., 2020 ). However, this study highlights for the first time that Type I TAs are equally important in facilitating adaptation of S .…”

Section: Section 1: Type I Toxin Antitoxin Systemsmentioning

confidence: 93%

RNA Regulated Toxin-Antitoxin Systems in Pathogenic Bacteria

Sarpong

Murphy

2021

Front. Cell. Infect. Microbiol.

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The dynamic host environment presents a significant hurdle that pathogenic bacteria must overcome to survive and cause diseases. Consequently, these organisms have evolved molecular mechanisms to facilitate adaptation to environmental changes within the infected host. Small RNAs (sRNAs) have been implicated as critical regulators of numerous pathways and systems in pathogenic bacteria, including that of bacterial Toxin-Antitoxin (TA) systems. TA systems are typically composed of two factors, a stable toxin, and a labile antitoxin which functions to protect against the potentially deleterious activity of the associated toxin. Of the six classes of bacterial TA systems characterized to date, the toxin component is always a protein. Type I and Type III TA systems are unique in that the antitoxin in these systems is an RNA molecule, whereas the antitoxin in all other TA systems is a protein. Though hotly debated, the involvement of TA systems in bacterial physiology is recognized by several studies, with the Type II TA system being the most extensively studied to date. This review focuses on RNA-regulated TA systems, highlighting the role of Type I and Type III TA systems in several pathogenic bacteria.

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RHS-elements function as type II toxin-antitoxin modules that regulate intra-macrophage replication of Salmonella Typhimurium

Cited by 10 publications

References 58 publications

Immunity proteins of dual nuclease T6SS effectors function as transcriptional repressors

Immunity proteins of dual nuclease T6SS effectors function as transcriptional repressors

Two Type VI Secretion Systems of Enterobacter cloacae Are Required for Bacterial Competition, Cell Adherence, and Intestinal Colonization

RNA Regulated Toxin-Antitoxin Systems in Pathogenic Bacteria

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