Modeling colicin operons as genetic arms in plasmid-genome conflicts

Mapping Intimacies ◽

10.1101/2021.05.15.444200 ◽

2021 ◽

Author(s):

Pavithra Anantharaman Sudhakari ◽

Bhaskar Chandra Mohan Ramisetty

Keyword(s):

Negative Selection ◽

Bacterial Genome ◽

Evolutionary Perspective ◽

Bacterial Genomes ◽

Sequence Analyses ◽

Agent Based ◽

Physiological Relevance ◽

Maintenance Systems ◽

Selection Of ◽

Lethal Genes

Plasmids are acellular propagating entities that depend, as molecular parasites, on bacteria for propagation. The conflict between the bacterial genome and the parasitic plasmids allows the emergence of genetic arms such as Colicin (Col) operons. Endonuclease Col operons encode three proteins; an endonuclease colicin (cleaves nucleic acids), an immunity protein (inactivates its cognate colicin), and lysis protein (aids in colicin release via host cell lysis). Col operons are efficient plasmid-maintenance systems; (i) the plasmid cured cells are killed by the colicins; (ii) damaged cells lyse and releases the colicins that eliminate the competitors; and (iii) the released plasmids invade new bacteria. Surprisingly, some bacterial genomes have Col operons. The eco-evolutionary drive and physiological relevance of genomic Col operons are unknown. We investigated plasmidic and genomic Col operons using sequence analyses from an eco-evolutionary perspective. We found 1,248 genomic and plasmidic colicins across 30 bacterial genera. Although 51% of the genomes harbor colicins, the majority of the genomic colicins lacked a functional lysis gene, suggesting the negative selection of lethal genes. The immunity gene of the Col operon protects the cured host thereby eliminating the metabolic burden due to plasmid. We show mutual exclusivity of col operons on genomes and plasmids. We propose anti-addiction hypothesis for genomic colicins. Using a stochastic agent-based model, we show that the genomic colicins confer an advantage to the host genome in terms of immunity to the toxin and elimination of plasmid burden. Col operons are genetic arms that regulate the ecological interplay of bacterial genomes and plasmids.

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Modeling Colicin Operons as Genetic Arms in Plasmid-genome Conflicts

10.21203/rs.3.rs-853467/v1 ◽

2021 ◽

Author(s):

Pavithra Anantharaman Sudhakari ◽

Bhaskar Chandra Mohan Ramisetty

Keyword(s):

Negative Selection ◽

Bacterial Genome ◽

Evolutionary Perspective ◽

Bacterial Genomes ◽

Sequence Analyses ◽

Agent Based ◽

Physiological Relevance ◽

Maintenance Systems ◽

Selection Of ◽

Lethal Genes

Abstract Plasmids are acellular propagating entities that depend on bacteria, as molecular parasites, for propagation. A 'tussle' between bacteria and plasmid ensues; bacteria for riddance of the plasmid and plasmid for persistence within a live host. The conflict between bacterial genome and plasmids allows the emergence of 'genetic arms' such as colicin (Col) operons. Endonuclease Col operons encode three proteins; an endonuclease colicin, an immunity protein, and lysis protein. Col operons are plasmid-maintenance systems; (i) the plasmid-cured cells are killed by the colicins; (ii) damaged cells lyse and release the colicins that eliminate the competitors, and (iii) the released plasmids invade new bacteria. Surprisingly, some bacterial genomes have Col operons. The eco-evolutionary drive and physiological relevance of genomic Col operons are unknown. We investigated plasmidic and genomic Col operons using sequence analyses from an eco-evolutionary perspective. We found 1,248 genomic and plasmidic colicins across 30 bacterial genera. Although 51% of the genomes harbor colicins, the majority of the genomic colicins lacked a functional lysis gene, suggesting the negative selection of lethal genes. The immunity gene of the Col operon protects the plasmid-cured host; eliminating the metabolic burden. We show mutual exclusivity of Col operons on genomes and plasmids. We propose an anti-addiction hypothesis for genomic colicins. Using a stochastic agent-based model, we show that the genomic colicins confer an advantage to the host genome in terms of immunity to the toxin and elimination of plasmid burden. Col operons are 'genetic arms' that regulate the ecological interplay of bacterial genomes and plasmids.

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From Anti-EBV Immune Responses to the EBV Diseasome via Cross-reactivity

Global Medical Genetics ◽

10.1055/s-0040-1715641 ◽

2020 ◽

Vol 07 (02) ◽

pp. 051-063

Author(s):

Darja Kanduc ◽

Yehuda Shoenfeld

Keyword(s):

Immune Responses ◽

Negative Selection ◽

Epstein Barr Virus ◽

Cross Reactivity ◽

Sequence Analyses ◽

Barr Virus ◽

Human Proteins ◽

Epstein Barr ◽

Reactive Lymphocytes ◽

Selection Of

AbstractSequence analyses highlight a massive peptide sharing between immunoreactive Epstein-Barr virus (EBV) epitopes and human proteins that—when mutated, deficient or improperly functioning—associate with tumorigenesis, diabetes, lupus, multiple sclerosis, rheumatoid arthritis, and immunodeficiencies, among others. Peptide commonality appears to be the molecular platform capable of linking EBV infection to the vast EBV-associated diseasome via cross-reactivity and questions the hypothesis of the “negative selection” of self-reactive lymphocytes. Of utmost importance, this study warns that using entire antigens in anti-EBV immunotherapies can associate with autoimmune manifestations and further supports the concept of peptide uniqueness for designing safe and effective anti-EBV immunotherapies.

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In vitro negative selection of viral superantigen-reactive TCR transgenic thymocytes by thymic dendritic cells

Immunology Letters ◽

10.1016/s0165-2478(97)87831-5 ◽

1997 ◽

Vol 56 (1-3) ◽

pp. 249

Author(s):

I Ferrero

Keyword(s):

Dendritic Cells ◽

Negative Selection ◽

Selection Of

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Serodiagnosis and Bacterial Genome of Helicobacter pylori Infection

Toxins ◽

10.3390/toxins13070467 ◽

2021 ◽

Vol 13 (7) ◽

pp. 467

Author(s):

Aina Ichihara ◽

Hinako Ojima ◽

Kazuyoshi Gotoh ◽

Osamu Matsushita ◽

Susumu Take ◽

...

Keyword(s):

Helicobacter Pylori ◽

Antibody Titer ◽

Bacterial Genome ◽

Serum Antibody ◽

Gene Mutations ◽

Bacterial Genomes ◽

Western Blots ◽

A Genome ◽

Vaca Gene ◽

H Pylori

The infection caused by Helicobacter pylori is associated with several diseases, including gastric cancer. Several methods for the diagnosis of H. pylori infection exist, including endoscopy, the urea breath test, and the fecal antigen test, which is the serum antibody titer test that is often used since it is a simple and highly sensitive test. In this context, this study aims to find the association between different antibody reactivities and the organization of bacterial genomes. Next-generation sequences were performed to determine the genome sequences of four strains of antigens with different reactivity. The search was performed on the common genes, with the homology analysis conducted using a genome ring and dot plot analysis. The two antigens of the highly reactive strains showed a high gene homology, and Western blots for CagA and VacA also showed high expression levels of proteins. In the poorly responsive antigen strains, it was found that the inversion occurred around the vacA gene in the genome. The structure of bacterial genomes might contribute to the poor reactivity exhibited by the antibodies of patients. In the future, an accurate serodiagnosis could be performed by using a strain with few gene mutations of the antigen used for the antibody titer test of H. pylori.

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Consistent Metagenome-Derived Metrics Verify and Delineate Bacterial Species Boundaries

mSystems ◽

10.1128/msystems.00731-19 ◽

2020 ◽

Vol 5 (1) ◽

Cited By ~ 14

Author(s):

Matthew R. Olm ◽

Alexander Crits-Christoph ◽

Spencer Diamond ◽

Adi Lavy ◽

Paula B. Matheus Carnevali ◽

...

Keyword(s):

Bacterial Diversity ◽

Ribosomal Proteins ◽

Large Scale ◽

Bacterial Species ◽

Bacterial Genome ◽

16S Rrna Genes ◽

Rrna Genes ◽

Species Discrimination ◽

Bacterial Genomes ◽

Discrimination Power

ABSTRACT Longstanding questions relate to the existence of naturally distinct bacterial species and genetic approaches to distinguish them. Bacterial genomes in public databases form distinct groups, but these databases are subject to isolation and deposition biases. To avoid these biases, we compared 5,203 bacterial genomes from 1,457 environmental metagenomic samples to test for distinct clouds of diversity and evaluated metrics that could be used to define the species boundary. Bacterial genomes from the human gut, soil, and the ocean all exhibited gaps in whole-genome average nucleotide identities (ANI) near the previously suggested species threshold of 95% ANI. While genome-wide ratios of nonsynonymous and synonymous nucleotide differences (dN/dS) decrease until ANI values approach ∼98%, two methods for estimating homologous recombination approached zero at ∼95% ANI, supporting breakdown of recombination due to sequence divergence as a species-forming force. We evaluated 107 genome-based metrics for their ability to distinguish species when full genomes are not recovered. Full-length 16S rRNA genes were least useful, in part because they were underrecovered from metagenomes. However, many ribosomal proteins displayed both high metagenomic recoverability and species discrimination power. Taken together, our results verify the existence of sequence-discrete microbial species in metagenome-derived genomes and highlight the usefulness of ribosomal genes for gene-level species discrimination. IMPORTANCE There is controversy about whether bacterial diversity is clustered into distinct species groups or exists as a continuum. To address this issue, we analyzed bacterial genome databases and reports from several previous large-scale environment studies and identified clear discrete groups of species-level bacterial diversity in all cases. Genetic analysis further revealed that quasi-sexual reproduction via horizontal gene transfer is likely a key evolutionary force that maintains bacterial species integrity. We next benchmarked over 100 metrics to distinguish these bacterial species from each other and identified several genes encoding ribosomal proteins with high species discrimination power. Overall, the results from this study provide best practices for bacterial species delineation based on genome content and insight into the nature of bacterial species population genetics.

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A Role for Fas in Negative Selection of Thymocytes In Vivo

Journal of Experimental Medicine ◽

10.1084/jem.187.9.1427 ◽

1998 ◽

Vol 187 (9) ◽

pp. 1427-1438 ◽

Cited By ~ 112

Author(s):

Hidehiro Kishimoto ◽

Charles D. Surh ◽

Jonathan Sprent

Keyword(s):

Negative Selection ◽

Cell Receptor ◽

Staphylococcal Enterotoxin B ◽

Thymic Medulla ◽

Enterotoxin B ◽

High Doses ◽

Specific Peptide ◽

Selection Of

To seek information on the role of Fas in negative selection, we examined subsets of thymocytes from normal neonatal mice versus Fas-deficient lpr/lpr mice injected with graded doses of antigen. In normal mice, injection of 1–100 μg of staphylococcal enterotoxin B (SEB) induced clonal elimination of SEB-reactive Vβ8+ cells at the level of the semi-mature population of HSAhi CD4+ 8− cells found in the thymic medulla; deletion of CD4+ 8+ cells was minimal. SEB injection also caused marked elimination of Vβ8+ HSAhi CD4+ 8− thymocytes in lpr/lpr mice. Paradoxically, however, elimination of these cells in lpr/lpr mice was induced by low-to-moderate doses of SEB (≤1 μg) but not by high doses (100 μg). Similar findings applied when T cell receptor transgenic mice were injected with specific peptide. These findings suggest that clonal elimination of semi-mature medullary T cells is Fas independent at low doses of antigen but Fas dependent at high doses. Previous reports documenting that negative selection is not obviously impaired in lpr/lpr mice could thus reflect that the antigens studied were expressed at only a low level.

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