Special Issue "Bacterial Toxins: Protein Folding and Membrane Interactions"
Deadline for manuscript submissions: 30 September 2021.
Bacterial toxins foster infection and disease by altering host tissues and by subverting the host immune response. They diffuse through compartments of various compositions, may cross several membranes to reach their target location, and finally have to properly fold into a functional state. Hence, large conformational changes occur between the sites of toxin biosynthesis and their target locations. Recent results illustrate how bacterial toxins are characterized by structural flexibility, which is essential at various steps, such as toxin secretion, folding, insertion into host membranes, transport across membranes into target cells, etc.
These structural transitions are finely tuned to the environmental conditions that bacterial toxins successively experience along their journey from bacterium cytoplasm to target location. For instance, they are able to unfold to go through narrow channels of bacterial secretion systems. Some bacterial toxins interact with host membranes due to the presence of particular lipids that confer properties modulating membrane fluidity, curvature, and charge; these properties switch these bacterial toxins from a resting to an active state. Some toxins are also sensitive to the presence of a membrane potential, a cell receptor, an electrochemical gradient, lipid asymmetry, etc. These environmental parameters trigger conformational changes of bacterial toxins required for host cell intoxication.
Finally, recent methodological advances and scientific results in bacterial toxins have opened new perspectives for basic sciences and toxin-based biotechnological applications. Taken together, the aim of this Special Issue of Toxins is to discuss these various aspects on folding and membrane interactions of bacterial toxins.
Dr. Alexandre Chenal
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 2400 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.
- bacterial toxins
- protein folding
- structural disorder
- membrane-induced conformational change
- toxin membrane interactions
- membrane insertion of toxins
- toxin translocation across membrane
- membrane-induced shape-shifting toxins
- Amphitropic toxins
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.
1.Title: Structural Basis and Functional Implications of the Pore-Forming Toxin: Membrane Interaction
Authors: Yajuan Li; Ying Huang; Yuanhong Xu*; Tengchuan Jin
Affiliation: Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Abstract: With the emerging of antibiotic-resistant bacteria, it is of urgent need to discovery targets for anti-bacterial therapy. Pore-forming toxin (PFTs) are the largest family of bacterial virulence factors produced by many pathogenic bacteria and constitute a major and best characterized class of pore-forming proteins (PFPs), which were found in all biological kingdom. Recent studies revealed structural mechanism of several PFTs in state of soluble inactive monomers and transmembrane oligomers. Upon interacting with host cells, soluble monomer of bacterial PFTs assemble into transmembrane oligomeric complexes with the capacity to insert into membranes and affect target cell-membrane permeability, which leading to diverse cellular responses and outcomes. In this review, we focus on the structural mechanisms of pore formation of PFTs at atomic level, and their interactions with host cells. We also discuss the functional implications of PFTs, eventually develop novel therapeutic strategies by targeting PFTs oligomerization or membrane receptor interactions. Keywords: Pore forming toxin; hemolysin; multi-drug resistance;
2. Title: Bacterial Type I Toxins: Folding and Membrane Interactions
Authors: Brice Felden1 *; Sylvie Nonin-Lecomte 2; Marie-Laure Pinel-Marie1 *
Affiliation: 1. Inserm, BRM (Bacterial Regulatory RNAs and Medicine) - UMR_S 1230, 35000 Rennes, France; 2. CNRS, CiTCoM – UMR_8038, 75270, Paris, France;
Abstract: Bacterial type I toxin-antitoxin systems are two-component genetic modules that encode a stable toxic protein whose ectopic overexpression can lead to growth arrest or cell death, and a unstable RNA antitoxin which inhibits the toxin’s translation during growth. Type I antitoxins are cis- or trans-encoded antisense small RNAs that interact with toxin-encoding mRNAs by pairing, thereby inhibiting toxin mRNA translation and/or inducing its degradation. Under environmental stress conditions, the up-regulation of the toxin and/or the antitoxin degradation by specific RNases induce toxin translation. Most type I toxins are small hydrophobic peptides with a predicted α-helical transmembrane domain that induce membrane depolarization by pore formation or by nucleoid condensation, leading to phage maintenance, growth adaptation to environmental stresses or persister cell formation. In this review, we describe the current state of the art on folding and membrane interactions of these membrane-associated type I toxins. We will also investigate by NMR and by dynamic simulation the structure of the SprG1- encoded membrane peptides that belongs to the sprG1/SprF1 type I TA system expressed in Staphylococcus aureus, and discuss the putative membrane interactions allowing the lysis of competing bacteria and of the host cells.
3. Title: Phylogenetic analysis of Filifactor alocis strains isolated from several oral infections identified a novel RTX toxin, FtxA
Authors: Jan Oscarsson; Rolf Claesson; Kai Bao; Malin Brundin; Georgios N. Belibasakis
Affiliation: Division of Oral Microbiology, Department of Odontology, Umeå University, Umeå
Abstract: Filifactor alocis is a Gram-positive asaccharolytic, obligate anaerobic rod of the phylum Firmicutes, and is considered an emerging pathogen in various oral infections, including periodontitis. We here aimed to perform phylogenetic analysis of a genome-sequenced F. alocis type strain (ATCC 35896; CCUG 47790), as well as nine clinical oral strains that we have independently isolated and sequenced, for identification and deeper characterization of novel genomic elements of virulence in this species. We identified that 60% of the strains carried a gene encoding a hitherto unrecognized member of the large repeats-in-toxins (RTX) family, which we have designated as FtxA. The clinical infection origin of the ftxA-positive isolates largely varied. However, a clear monophylogeny was reveled for all ftxA-positive strains, along with a high co-occurrence of lactate dehydrogenase (ldh)-positivity. Cloning and purification of the ftxA gene product yielded a protein of the predicted molecular size of approximately 250 kDa. The protein sequence was found to contain serralysin-like metallo-protease conserved domains, and proteolytic activity of purified FtxA was detected using a specific enzymatic assay. Additional experimental work involving genomic and proteomic analyses may reveal a possible role and mechanism(s) of FtxA in the virulence properties of F. alocis, and whether the gene might be a candidate diagnostic marker for more virulent strains.
4. Title: Pathogenic pore forming proteins of Plasmodium triggers the necrosis of Endothelial Cells attributed to malaria severity
Authors: Abhishek Shivappagowdar; Swati Garg; Akriti Srivastava; Rahul S. Hada; Lalit C. Garg; Soumya Pati; Shailja Singh
Affiliation: Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India
Abstract: Severe malaria caused by Plasmodium falciparum poses a major global health problem with high morbidity and mortality. The P. falciparum harbours a family of pore-forming proteins (PFPs), known as perforin like proteins (PLPs), which are structurally equivalent to prokaryotic PFPs. These PLPs are secreted from the parasites and by interacting with host cells they contribute to disease pathogenesis. The severe malaria pathogenesis is associated with the dysfunction of various barrier cells including endothelial cells. Several factors, including PLPs, secreted by parasites contribute to the host cell dysfunction. Herein, we tested the hypothesis that the PLPs mediate dysfunction of barrier cells and might have a role in disease pathogenesis. We analysed various dysfunction in barrier cells following rPLP2 exposure and demonstrate that it causes an increase in intracellular Ca2+ levels. Additionally, rPLP2 exposed barrier cells displayed features of cell death including Annexin/PI positivity, depolarized the mitochondrial membrane potential and ROS generation. We further performed the time-lapse video microscopy of barrier cells and found the treatment of rPLP2 triggers their membrane blebbing. The cytoplasmic localization of HMGB1, a marker of necrosis, further confirmed the necrotic type of cell death. This study highlights the role of parasite factor PLP in endothelial dysfunction and provides a rationale for the design of adjunct therapies against severe malaria.
5. Authors: Alexandre Chenal
Affiliation: Unité de Biochimie des Interactions Moléculaires, Institut Pasteur, CNRS, UMR 3528, 75015, Paris, France
6. Authors: William A. Cramer
Affiliation: Department of Biological Sciences, Hockmeyer Hall of Structural Biology, Purdue University, West Lafayette, IN 47907, USA
7. Authors: Nathalie Dautin
Affiliation: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ. Paris‐Sud, Université Paris‐Saclay, 91198, Gif‐sur‐Yvette cedex, France
8. Title: Structure and Folding of the Diphtheria Toxin Translocation Domain at Neutral and Acidic pH
Authors: Alexey Ladokhin
Affiliation: Department of Biochemistry and Molecular Biology; The University of Kansas Medical Center; 3901 Rainbow Blvd. 1073 HLSIC; Mailstop 3030; Kansas City; KS 66160-7421; USA
9. Authors: Rene Koeffel
Affiliation: Institute of Anatomy, University of Bern, Switzerlan
10. Title: Two-component bacterial toxin membrane translocation and their practical applications
Authors: Oksana Sergeeva
Affiliation: Group of Gisou van der Goot; Global Health Institute - School of Life Sciences; EPFL - Lausanne, Switzerland
11. Authors: Sebastien Brier
Affiliation: Institut Pasteur, UMR CNRS 3528, Chemistry and Structural Biology Department, 75724 PARIS cedex 15, France
12. Authors: Gregor Anderluh
Affiliation: Laboratory for Molecular Biology and Nanobiotechnology, National Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana, Slovenia