Proteic toxin-antitoxin, bacterial plasmid addiction systems and their evolution with special reference to the pas system of pTF-FC2

Rawlings, D

doi:10.1016/s0378-1097(99)00256-6

Cited by 17 publications

(19 citation statements)

References 43 publications

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“…No other known T4CP is essential for viability. Moreover, the only proteins associated with conjugative transfer that that are required for bacterial viability are inhibitors of plasmid toxin segregation factors (43). DotL, however, shows no sequence similarity to such factors.…”

Section: Discussionmentioning

confidence: 99%

The DotL Protein, a Member of the TraG-Coupling Protein Family, Is Essential for Viability ofLegionella pneumophilaStrain Lp02

et al. 2005

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Legionella pneumophila is able to survive inside phagocytic cells by an internalization route that bypasses fusion of the nascent phagosome with the endocytic pathway to allow formation of a replicative phagosome. The dot/icm genes, a major virulence system of L. pneumophila, encode a type IVB secretion system that is required for intracellular growth. One Dot protein, DotL, has sequence similarity to type IV secretion system coupling proteins (T4CPs). In other systems, coupling proteins are not required for viability of the organism. Here we report the first example of a strain, L. pneumophila Lp02, in which a putative T4CP is essential for viability of the organism on bacteriological media. This result is particularly surprising since the majority of the dot/icm genes in Lp02 are dispensable for growth outside of a host cell, a condition that does not require a functional Dot/Icm secretion complex. We were able to isolate suppressors of the ⌬dotL lethality and found that many contained mutations in other components of the Dot/Icm secretion system. A systematic analysis of dot/icm deletion mutants revealed that the majority of them (20 of 26) suppressed the lethality phenotype, indicating a partially assembled secretion system may be the source of ⌬dotL toxicity in the wild-type strain. These results are consistent with a model in which the DotL protein plays a role in regulating the activity of the L. pneumophila type IV secretion apparatus.The gram-negative bacterium Legionella pneumophila is the causative agent of a potentially fatal form of pneumonia called Legionnaires' disease. L. pneumophila is found in freshwater environments, where it parasitizes many different species of protozoa (17). Humans become infected with L. pneumophila by inhaling aerosols generated from contaminated water sources. Upon entry into the human lung, L. pneumophila is internalized into bactericidal, alveolar macrophages. In contrast to phagosomes bearing most bacterial species, the compartment harboring L. pneumophila does not traffic into the lysosomal network and is not significantly acidified in the first few hours after uptake (26,27). Instead, the phagosome interacts with early secretory vesicles at endoplasmic reticulum exit sites (29) and then undergoes a series of maturation events in which it sequentially associates with small vesicles, mitochondria, and eventually becomes surrounded by the rough endoplasmic reticulum (25, 60). Formation of this specialized compartment, called a "replicative phagosome," allows the microorganism to grow intracellularly (25, 28). Later in the infective cycle, a majority of the replicative phagosomes fuse with acidified compartments containing late endocytic markers, and this is believed to play an important role in the replicative cycle of this pathogen prior to exit from its host cell (59).The key to L. pneumophila's virulence is its ability to form a replicative phagosome, since mutants defective in this trait cannot replicate inside host cells and are thus unable to cause disease (24,26...

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Section: Discussionmentioning

confidence: 99%

The DotL Protein, a Member of the TraG-Coupling Protein Family, Is Essential for Viability ofLegionella pneumophilaStrain Lp02

et al. 2005

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“…Plasmid-addiction systems are genetic entities of low-copynumber plasmids (for reviews, see [1][2][3][4][5][6]) that selectively kill plasmid-free cells and thus mediate stable inheritance of the plasmid in bacteria. They consist of an operon coding for two small proteins, acting as a toxin and an anti-toxin.…”

Section: Introductionmentioning

confidence: 99%

“…The parDE operon of broad-host-range plasmid RP4\RK2 constitutes such a plasmid-addiction system and has been characterized in terms of genetics and function [8,9], together with other killing modules of extrachromosomal elements. Recent studies include ccd of plasmid F [10], parD and pem of plasmids R1 and R100 [11], phd\doc of prophage P1 [12] and pas of plasmid pTF-FC2 [4].…”

Section: Introductionmentioning

confidence: 99%

The anti-toxin ParD of plasmid RK2 consists of two structurally distinct moieties and belongs to the ribbon-helix-helix family of DNA-binding proteins

Oberer

Zangger

PRYTULLA³

et al. 2001

Biochemical Journal

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NMR and CD spectroscopy have been used to characterize, both structurally and dynamically, the 82-amino-acid ParD protein of the post-segregational killing module of the broad-host-range plasmid RP4\RK2. ParD occurs as a dimer in solution and exercises two different control functions ; an autoregulatory function by binding to its own promoter P parDE and a plasmidstabilizing function by inhibiting ParE toxicity in cells that express ParD and ParE. Analysis of the secondary structure based on the chemical-shift indices, sequential nuclear Overhauser enhancements (NOEs) and $J H α -NH scalar coupling constants showed that the N-terminal domain of ParD consists of a short β-ribbon followed by three α-helices, demonstrating that ParD contains a ribbon-helix-helix fold, a DNA-binding motif found in a family of small prokaryotic repressors. "&N longitudinal

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“…Indeed, the concept of a fitness cost of expressing, or simply carrying, resistance genes is not a paradigm anymore. Mechanisms to retain resistance markers along with other genetic determinants have been proposed on the basis of a toxin-antitoxin system [3] (killing the daughter cells that lose the plasmid) similar to a mechanism that mediates persistence. Whatever the mechanism, persistence of resistance is reflected in recent observations in selected settings in which reduced utilization of antibiotics failed to lower the prevalence of resistance determinants [4], which are prompting a shift in strategies to circumvent a phenomenon that proves to be hardly reversible once started.…”

Section: Antibiotic Resistance As An Environmental Issuementioning

confidence: 99%

Resistance genes traveling the microbial internet: down the drain, up the food chain?

Cassone

Giordano

2009

Expert Review of Anti-infective Therapy

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Proteic toxin-antitoxin, bacterial plasmid addiction systems and their evolution with special reference to the pas system of pTF-FC2

Cited by 17 publications

References 43 publications

The DotL Protein, a Member of the TraG-Coupling Protein Family, Is Essential for Viability ofLegionella pneumophilaStrain Lp02

The DotL Protein, a Member of the TraG-Coupling Protein Family, Is Essential for Viability ofLegionella pneumophilaStrain Lp02

The anti-toxin ParD of plasmid RK2 consists of two structurally distinct moieties and belongs to the ribbon-helix-helix family of DNA-binding proteins

Resistance genes traveling the microbial internet: down the drain, up the food chain?

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