Special Issue "Toxin-Antitoxin Systems in Pathogenic Bacteria"

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Bacterial Toxins".

Deadline for manuscript submissions: 31 July 2020.

Special Issue Editor

Prof. Dr. Juan Carlos Alonso

Guest Editor
National Centre for Biotechnology (CNB-CSIC), Cantoblanco, 28048 Madrid, Spain
Interests: We investigated the functionalities, regulation of the type II toxin ζ derived from Streptococcus/Enterococcus genera, and the possible cross-talk between ζ and function involved in stress response. We used a combination of genetic, biochemical, structural studies, molecular docking, and mutational analysis to understand the mode of action and substrate recognition by toxin ζ

Special Issue Information

Dear Colleagues,

Bacterial toxin–antitoxin (TA) systems, which are ubiquitously present in bacterial genomes, are not essential for normal cell proliferation. The TAs regulate fundamental cellular processes, facilitate survival under stress conditions, have essential roles in persistence and virulence, and represent potential therapeutic targets. These genetic TA loci are also shown to be involved in the maintenance of successful multidrug-resistant mobile genetic elements. TA systems encode a labile antitoxin and its stable toxin; degradation of the antitoxin renders a free toxin, which is bacteriostatic by nature. A free toxin generates a reversible state with low metabolic activity (quiescence) by affecting important functions of bacterial cells such as transcription, translation, DNA replication, replication and cell–wall synthesis, biofilm formation, phage predation, the regulation of nucleotide pool, etc., whereas antitoxins are toxin inhibitors. Under stress conditions, the TA systems might form networks. Understanding the basis of the unique response of TAs to stress, the prime causes for the emergence of drug-resistant strains, and their contribution to therapy failure and development of chronic and recurrent infections are necessary to grasp how TAs contribute to the mechanisms of phenotypic heterogeneity and pathogenesis that will enable the development of rational development of new treatment for infections caused by pathogens.

Prof. Dr. Juan Carlos Alonso
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a double-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxins is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • stable toxin
  • labile antitoxin
  • bacteriostatic TA mechanism
  • bacterial persistence
  • multidrug-resistant hospital infections
  • antibacterial strategy

Published Papers (1 paper)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Open AccessArticle
Multi-Stress Induction of the Mycobacterium tuberculosis MbcTA Bactericidal Toxin-Antitoxin System
Toxins 2020, 12(5), 329; https://doi.org/10.3390/toxins12050329 - 16 May 2020
Abstract
MbcTA is a type II toxin/antitoxin (TA) system of Mycobacterium tuberculosis. The MbcT toxin triggers mycobacterial cell death in vitro and in vivo through the phosphorolysis of the essential metabolite NAD+ and its bactericidal activity is neutralized by physical interaction with [...] Read more.
MbcTA is a type II toxin/antitoxin (TA) system of Mycobacterium tuberculosis. The MbcT toxin triggers mycobacterial cell death in vitro and in vivo through the phosphorolysis of the essential metabolite NAD+ and its bactericidal activity is neutralized by physical interaction with its cognate antitoxin MbcA. Therefore, the MbcTA system appears as a promising target for the development of novel therapies against tuberculosis, through the identification of compounds able to antagonize or destabilize the MbcA antitoxin. Here, the expression of the mbcAT operon and its regulation were investigated. A dual fluorescent reporter system was developed, based on an integrative mycobacterial plasmid that encodes a constitutively expressed reporter, serving as an internal standard for monitoring mycobacterial gene expression, and an additional reporter, dependent on the promoter under investigation. This system was used both in M. tuberculosis and in the fast growing model species Mycobacterium smegmatis to: (i) assess the autoregulation of mbcAT; (ii) perform a genetic dissection of the mbcA promoter/operator region; and (iii) explore the regulation of mbcAT transcription from the mbcA promoter (PmbcA) in a variety of stress conditions, including in vivo in mice and in macrophages. Full article
(This article belongs to the Special Issue Toxin-Antitoxin Systems in Pathogenic Bacteria)
Show Figures

Figure 1

Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Type of Paper: Article
Title: Toxin zeta persisters are not epistatic to antibiotic persisters
Authors: María Moreno-del Alamo and Juan C. Alonso

Affliation: National Centre for Biotechnology (CNB-CSIC), Cantoblanco, 28048 Madrid, Spain

 

Type of Paper: Article
Title: Multi-stress induction of the MbcAT bactericidal toxin-antitoxin system of Mycobacterium tuberculosis
Authors: Claude Gutierrez, Olivier Neyrolles

Affiliation: Institute of Pharmacology and Structural Biology, Toulouse, France

Abstract: MbcAT is a type II toxin/antitoxin (TA) system of Mycobacterium tuberculosis. The MbcT toxin trigger mycobacterial cells death through the phosphorolysis of the essential metabolite NAD+ and interaction of MbcA with MbcT in a dodecameric complex results in toxin neutralization. Here, the expression of the mbcAT operon and its regulation were investigated. A dual fluorescent reporter system was developed, based on an integrative mycobacterial plasmid that encodes a constitutively expressed reporter, serving as an internal standard of mycobacterial gene expression, and a second reporter, dependent on the promoter under investigation. This system was used, either in M. tuberculosis or in the fast growing model species M. smegmatis to: i) characterize the autoregulation of mbcAT; ii) perform a genetic dissection of the mbcA promoter/operator region and iii) demonstrate the up-regulation of transcription from the mbcA promoter (PmbcA) in a variety of stress conditions, including infection of mice or human macrophages. Obtained results have documented bactericidal effect of MbcT during infection. Therefore, the MbcTA TA system appears to be a promising target for development of novel therapies against tuberculosis through the identification of compounds able to neutralize or destabilize the MbcA antitoxin.

Keywords: Tuberculosis; toxin-antitoxin systems; bacterial cell death; NAD+; stress-response

Key Contribution: A dual fluorescent reporter system, designed to monitor gene expression and regulation in mycobacteria was constructed and used to analyze the multi-stress regulation of the MbcAT bactericidal toxin/antitoxin system of Mycobacterium tuberculosis.

 

Type of Paper: Article
Title: Functional characterization of pemI-pemK toxin-antitoxin in pathogenic Agrobacterium tumefaciens
Authors: Jung-Ho Park and co-authors

Affliation: Korea Research Institute of Bioscience and Biotechnology(KRIBB), 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Cheongju-si, Chungbuk, 28116, South Korea

Back to TopTop