Bacterial Toxin–Antitoxin Systems: More Than Selfish Entities?

Melderen, Laurence Van; Bast, Manuel Saavedra De

doi:10.1371/journal.pgen.1000437

Cited by 437 publications

(407 citation statements)

References 59 publications

Supporting

Mentioning

400

Contrasting

Order By: Relevance

“…However, the potential risk of underestimation of the prevalence of TA loci in the clinical E. coli isolates must be taken into consideration due to sequence variations of either toxin or antitoxin genes at primer annealing sites, and/or diverse configurations of the genes in bacterial genomes (Van Melderen & Saavedra De Bast, 2009;Leplae et al, 2011). To date, only Norton & Mulvey (2012) have observed that uropathogenic B2 coli genome, and the order of rings/genomes in E. coli phylogroups, starting from the innermost one, was included in Table S1.…”

Section: Discussionmentioning

confidence: 99%

Type II toxin–antitoxin systems are unevenly distributed among Escherichia coli phylogroups

et al. 2015

View full text Add to dashboard Cite

Type II toxin-antitoxin systems (TAs) are bicistronic operons ubiquitous in prokaryotic genomes, displaying multilevel association with cell physiology. Various possible functions have been assigned to TAs, ranging from beneficial for their hosts, such as a stress response, dormancy and protection against genomic parasites, to detrimental or useless functions, such as selfish alleles. As there is a link between several Escherichia coli features (e.g. virulence, lifestyle) and the phylogeny of this species, we hypothesized a similar association with TAs. Using PCR we studied the distribution of 15 chromosomal and plasmidic type II TA loci in 84 clinical E. coli isolates in relation to their main phylogenetic groups (A, B1, B2 and D). In addition, we performed in silico searching of these TA loci in 60 completely sequenced E. coli genomes deposited in GenBank. The highest number of TA loci per strain was observed in group A (mean 8.2, range 5-12) and the lowest in group B2 (mean 4.2, range 2-8). Moreover, significant differences in the prevalence of nine chromosomal TAs among E. coli phylogroups were noted. In conclusion, the presence of some chromosomal TAs in E. coli is phylogroup-related rather than a universal feature of the species. In addition, their limited collection in group B2 clearly distinguish it from the other E. coli phylogroups.

show abstract

Section: Discussionmentioning

confidence: 99%

Type II toxin–antitoxin systems are unevenly distributed among Escherichia coli phylogroups

et al. 2015

View full text Add to dashboard Cite

show abstract

“…An indirect mechanism was proposed in the case of the prevention of plasmid establishment (50). According to this model, a host cell harboring a chromosomally encoded antitoxin would neutralize the toxin of a plasmid-encoded T-A system and prevent plasmid addiction (50).…”

Section: Non-r-m Defense Systemsmentioning

confidence: 99%

Diverse Functions of Restriction-Modification Systems in Addition to Cellular Defense

Vasu

Nagaraja

2013

Microbiol Mol Biol Rev

509

462

View full text Add to dashboard Cite

SUMMARY Restriction-modification (R-M) systems are ubiquitous and are often considered primitive immune systems in bacteria. Their diversity and prevalence across the prokaryotic kingdom are an indication of their success as a defense mechanism against invading genomes. However, their cellular defense function does not adequately explain the basis for their immaculate specificity in sequence recognition and nonuniform distribution, ranging from none to too many, in diverse species. The present review deals with new developments which provide insights into the roles of these enzymes in other aspects of cellular function. In this review, emphasis is placed on novel hypotheses and various findings that have not yet been dealt with in a critical review. Emerging studies indicate their role in various cellular processes other than host defense, virulence, and even controlling the rate of evolution of the organism. We also discuss how R-M systems could have successfully evolved and be involved in additional cellular portfolios, thereby increasing the relative fitness of their hosts in the population.

show abstract

“…For the chromosomal ccd systems, these include the antiaddiction model (11), which states that the chromosomally encoded ccd system (ccd Ech ) protects the cell against postsegregational killing mediated by its F-plasmid ccd (ccd F ) homolog, whereas for the ccd O157 system, it has been suggested that this system is devoid of any biological role in the E. coli species (12). Models proposed for other chromosomal TA systems include the programmed cell death (PCD) model, the growth modulation model, the persistence model, and the development model (13). TA loci have been proposed as general stress response elements in prokaryotes (14)(15)(16)(17).…”

Section: Abstract Toxin-antitoxin Persistencementioning

confidence: 99%

Contribution of the Chromosomal ccdAB Operon to Bacterial Drug Tolerance

et al. 2017

View full text Add to dashboard Cite

One of the first identified and best-studied toxin-antitoxin (TA) systems in Escherichia coli is the F-plasmid-based CcdAB system. This system is involved in plasmid maintenance through postsegregational killing. More recently, ccdAB homologs have been found on the chromosome, including in pathogenic strains of E. coli and other bacteria. However, the functional role of chromosomal ccdAB genes, if any, has remained unclear. We show that both the native ccd operon of the E. coli O157 strain (ccd O157 ) and the ccd operon from the F plasmid (ccd F ), when inserted on the E. coli chromosome, lead to protection from cell death under multiple antibiotic stress conditions through formation of persisters, with the O157 operon showing higher protection. While the plasmid-encoded CcdB toxin is a potent gyrase inhibitor and leads to bacterial cell death even under fully repressed conditions, the chromosomally encoded toxin leads to growth inhibition, except at high expression levels, where some cell death is seen. This was further confirmed by transiently activating the chromosomal ccd operon through overexpression of an active-site inactive mutant of F-plasmid-encoded CcdB. Both the ccd F and ccd O157 operons may share common mechanisms for activation under stress conditions, eventually leading to multidrug-tolerant persister cells. This study clearly demonstrates an important role for chromosomal ccd systems in bacterial persistence.IMPORTANCE A large number of free-living and pathogenic bacteria are known to harbor multiple toxin-antitoxin systems, on plasmids as well as on chromosomes. The F-plasmid CcdAB system has been extensively studied and is known to be involved in plasmid maintenance. However, little is known about the function of its chromosomal counterpart, found in several pathogenic E. coli strains. We show that the native chromosomal ccd operon of the E. coli O157 strain is involved in drug tolerance and confers protection from cell death under multiple antibiotic stress conditions. This has implications for generation of potential therapeutics that target these TA systems and has clinical significance because the presence of persisters in an antibiotic-treated population can lead to resuscitation of chronic infection and may contribute to failure of antibiotic treatment.KEYWORDS toxin-antitoxin, persistence I n the early 1940s it was reported that a small fraction of staphylococcal cells, about one in a million, survived prolonged penicillin treatment (1). These cells were termed persisters. Later it was established that persisters are phenotypic variants in a given population that show antibiotic tolerance due to probable differences in their physiology under a given set of conditions. Upon subsequent culturing, they give rise to a population that retains antibiotic sensitivity. They are different from resistant cells in which resistance is genetically encoded and is passed on from one generation to the next. In contrast, persisters are transient and rare, ranging from 10 Ϫ2 to 10 Ϫ6 in frequenc...

show abstract

Bacterial Toxin–Antitoxin Systems: More Than Selfish Entities?

Cited by 437 publications

References 59 publications

Type II toxin–antitoxin systems are unevenly distributed among Escherichia coli phylogroups

Type II toxin–antitoxin systems are unevenly distributed among Escherichia coli phylogroups

Diverse Functions of Restriction-Modification Systems in Addition to Cellular Defense

Contribution of the Chromosomal ccdAB Operon to Bacterial Drug Tolerance

Contact Info

Product

Resources

About