Dataset Information

Charged Residues Flanking the Transmembrane Domain of Two Related Toxin-Antitoxin System Toxins Affect Host Response.

ABSTRACT: A majority of toxins produced by type I toxin-antitoxin (TA-1) systems are small membrane-localized proteins that were initially proposed to kill cells by forming non-specific pores in the cytoplasmic membrane. The examination of the effects of numerous TA-1 systems indicates that this is not the mechanism of action of many of these proteins. Enterococcus faecalis produces two toxins of the Fst/Ldr family, one encoded on pheromone-responsive conjugative plasmids (FstpAD1) and the other on the chromosome, FstEF0409. Previous results demonstrated that overexpression of the toxins produced a differential transcriptomic response in E. faecalis cells. In this report, we identify the specific amino acid differences between the two toxins responsible for the differential response of a gene highly induced by FstpAD1 but not FstEF0409. In addition, we demonstrate that a transporter protein that is genetically linked to the chromosomal version of the TA-1 system functions to limit the toxicity of the protein.

SUBMITTER: Holmes A

PROVIDER: S-EPMC8147318 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Charged Residues Flanking the Transmembrane Domain of Two Related Toxin-Antitoxin System Toxins Affect Host Response.

Holmes Andrew A Sadlon Jessie J Weaver Keith K

Toxins 20210501 5

A majority of toxins produced by type I toxin-antitoxin (TA-1) systems are small membrane-localized proteins that were initially proposed to kill cells by forming non-specific pores in the cytoplasmic membrane. The examination of the effects of numerous TA-1 systems indicates that this is not the mechanism of action of many of these proteins. <i>Enterococcus faecalis</i> produces two toxins of the Fst/Ldr family, one encoded on pheromone-responsive conjugative plasmids (Fst<sub>pAD1</sub>) and t ...[more]

PMID: 34062876

Similar Datasets

Project description:Rickettsia spp. can cause mild to severe human disease. These intracellular bacteria are associated with arthropods, nematodes and trematodes, and usually, are efficiently transmitted transovarially to the progeny of the invertebrate host. We recently demonstrated foreign gene acquisition by lateral gene transfer in Rickettsia genomes. The unexpected presence of laterally transferred toxin-antitoxin (TA) genetic elements (including vapBC) in several Rickettsia genomes has not been connected with the pathogenic process or the host-bacteria relationship. We suspect that vapBC are selfish genetic elements that addict eukaryotic hosts to Rickettsia. We identified a statistical link between the transovarial transmission of Rickettsia in invertebrate hosts and the presence of TA operons, specifically vapBC, in the Rickettsia genome. These TA are neighboring to type IV secretion genes. Tunel assays and whole-genome expression of infected cells showed that antibiotic eradication of TA-containing Rickettsia from the host in cell culture initiates a proapoptotic program. Rickettsia VapC toxins inhibit the growth of transformed Escherichia coli and Saccharomyces cerevisiae. Rickettsia toxin presents in vitro RNase activity. Annexin-V staining and time-lapse video showed that intracytoplasmic injections of VapC toxins in cells cause apoptosis. These data demonstrate that host cells may develop a dependence on Rickettsia spp. expressing the vapBC operon. This would constitute a new evolutionary M-bM-^@M-^\mafia strategyM-bM-^@M-^] of intracellular bacteria based on host addiction. Fresh cells from the human microvascular endothelial cell line (HMEC-1) [26] were infected with R. felis California-2 strain in the presence and absence of antibiotics, at a rate of 5 bacteria per eukaryotic cell. Then, we added or not antibiotics (chloramphenicol 50 M-BM-5g/ml or doxycycline to 40 M-BM-5g/ml) in both experimental (R.felis-infected) and control, mock-infected cells for 6 hours. The cells were harvested and RNA was extracted using the RNeasy Mini Kit (Qiagen). DNA contamination was removed using the Turbo DNA-free Kit (Ambion). RNA were labeled using the Quick Amp Labeling Kit One-color (Agilent) and hybridized onto a Whole Human Genome Microarray, 4x44K (Agilent) as recommended by the manufacturer. Arrays were scanned with DNA Microarray Scanner (Agilent), and data were extracted using Feature Extractor (Agilent).

Dataset Information

Charged Residues Flanking the Transmembrane Domain of Two Related Toxin-Antitoxin System Toxins Affect Host Response.

Publications

Charged Residues Flanking the Transmembrane Domain of Two Related Toxin-Antitoxin System Toxins Affect Host Response.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets