The mazEF toxin–antitoxin system as an attractive target in clinical isolates of Enterococcus faecium and Enterococcus faecalis

Abstract

The toxin–antitoxin (TA) system is a regulatory system where two sets of genes encode the toxin and its corresponding antitoxin. In this study, the prevalence of TA systems in independently isolated clinical isolates of Enterococcus faecium and Enterococcus faecalis was determined, the dominant TA system was identified, different virulence genes in E. faecium and E. faecalis were surveyed, the level of expression of the virulence and TA genes in normal and stress conditions was determined, and finally their associations with the TA genes were defined. Remarkably, the analysis demonstrated higBA and mazEF in all clinical isolates, and their locations were on chromosomes and plasmids, respectively. On the other hand, a quantitative analysis of TA and virulence genes revealed that the expression level in both genes is different under normal and stress conditions. The results obtained by anti-mazF peptide nucleic acids demonstrated that the expression level of virulence genes had decreased. These findings demonstrate an association between TA systems and virulence factors. The mazEF on the plasmids and the higBA TA genes on the chromosomes of all E. faecium and E. faecalis strains were dominant. Additionally, there was a decrease in the expression of virulence genes in the presence of anti-mazF peptide nucleic acids. Therefore, it is suggested that mazEF TA systems are potent and sensitive targets in all E. faecium and E. faecalis strains.

Plasmids Shaped the Recent Emergence of the Major Nosocomial Pathogen Enterococcus faecium

“…The widespread occurrence of these selfish systems is indicative of their importance in plasmid maintenance and stabilization. Previous reports have shown a high prevalence of particular toxin-antitoxin systems, such as mazEF, in E. faecium clinical isolates (33). They could contribute to the stabilization of plasmid-mediated antibiotic resistance by the maintenance of a single plasmid structure and might thus provide an interesting alternative target for antibiotic therapy.…”

Mechanisms of Bacterial Tolerance and Persistence in the Gastrointestinal and Respiratory Environments

“…Several plasmids encode toxin-antitoxin systems in strains of Enterococcus spp., as follows: (i) the plasmid pAD1-encoded Fst toxin (type I toxin-antitoxin) in E. faecalis affects the permeability of the membrane, thus altering the cellular responses to antibiotics (378)(379)(380)(381)(382); and (ii) plasmids encoding vancomycin resistance and harboring genes for the --Par toxin-antitoxin and Axe-Txe toxin-antitoxin have been located, but their involvement in the presence of persister cells has not been analyzed (383)(384)(385)(386). Moreover, mazEF, mazEG, and higBA loci have often been found in E. faecalis and Enterococcus faecium clinical strains (387).…”

Toxin-Antitoxin Systems in Clinical Pathogens

“…The Tac systems HigBA Ef and MazEF Ef have been located in the chromosome of E. faecalis and E. faecium clinical strains and found to be associated with the expression of virulence factors [ 25 ].…”