Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Cytoskeletoxins: Bacterial and Viral Effector Proteins Targeting the Cytoskeleton

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Toxicology".

Deadline for manuscript submissions: closed (30 November 2020) | Viewed by 16483

Share This Special Issue

Special Issue Editor

Dr. Dmitri S. Kudryashov

E-Mail Website
Guest Editor

Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA
Interests: actin cytoskeleton; bacterial toxins; antimicrobial peptides
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The ability to disrupt, manipulate, or hijack the cytoskeleton is a common feature of numerous bacterial and viral pathogens. These abilities developed in response to several factors, one of which is the remarkable functional and structural versatility of the cytoskeleton. As an essential and multifaceted component of both innate and adaptive immunity, a compromised cytoskeleton implies a compromised defense, which opens a direct route to abundant resources—the bona fide goal of all pathogens. Furthermore, F-actin and microtubules are tracks for myosin and kinesin motors, respectively, but also potent motors on their own. As such, they are an attractive source of mechanical power for entry, locomotion, spread, and egress of pathogens. The third reason the cytoskeleton is a common and attractive target for bacterial pathogens is its exceptionally high level of evolutionary conservation of the key elements of the eukaryotic cytoskeleton that are not found in bacteria. These properties ensure that once developed, the pathogenicity factors can be universally and specifically applied for targeting a vast number of eukaryotic hosts while remaining benign for the pathogens that produce them.

Several effector proteins/toxins produced by pathogenic bacteria and viruses are reasonably well understood and have become indispensable tools for revealing secrets of the cytoskeleton organization and function. Many are understood superficially, while still others remain to be discovered. In this Special Issue of IJMS, we invite research publications and review articles in a broad area at the interface between pathogens and the cytoskeleton that reveal novel details of the toxin pathogenicity, contribute to the understanding of the host, or summarize the existing knowledge on either of the two topics.

The word “cytoskeletoxins” in the title of this Special Issue cannot be found in dictionaries. It is meant to intrigue and attract the attention of potential authors and readers, but also to emphasize that the number of effector proteins targeting the cytoskeleton is so large and their role in the pathogenesis of various infectious diseases is so important that this group of effectors deserves to be given a very special name.

Dr. Dmitri S. Kudryashov
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 submissions that pass pre-check are 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 single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

toxin
effector
cytoskeleton
actin
tubulin
microtubules
actin binding proteins
microtubule-binding proteins
pathogenesis
signaling
tools
immunity

Published Papers (4 papers)

Download All Papers

Research

Jump to: Review

19 pages, 3250 KiB

Open AccessArticle

Rounding Out the Understanding of ACD Toxicity with the Discovery of Cyclic Forms of Actin Oligomers

by Harper Smith, Nick Pinkerton, David B. Heisler, Elena Kudryashova, Aaron R. Hall, Kelly R. Karch, Andrew Norris, Vicki Wysocki, Marcos Sotomayor, Emil Reisler, Dimitrios Vavylonis and Dmitri S. Kudryashov

Int. J. Mol. Sci. 2021, 22(2), 718; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22020718 - 13 Jan 2021

Cited by 4 | Viewed by 2594

Abstract

Actin is an essential element of both innate and adaptive immune systems and can aid in motility and translocation of bacterial pathogens, making it an attractive target for bacterial toxins. Pathogenic Vibrio and Aeromonas genera deliver actin cross-linking domain (ACD) toxin into the cytoplasm of the host cell to poison actin regulation and promptly induce cell rounding. At early stages of toxicity, ACD covalently cross-links actin monomers into oligomers (AOs) that bind through multivalent interactions and potently inhibit several families of actin assembly proteins. At advanced toxicity stages, we found that the terminal protomers of linear AOs can get linked together by ACD to produce cyclic AOs. When tested against formins and Ena/VASP, linear and cyclic AOs exhibit similar inhibitory potential, which for the cyclic AOs is reduced in the presence of profilin. In coarse-grained molecular dynamics simulations, profilin and WH2-motif binding sites on actin subunits remain exposed in modeled AOs of both geometries. We speculate, therefore, that the reduced toxicity of cyclic AOs is due to their reduced configurational entropy. A characteristic feature of cyclic AOs is that, in contrast to the linear forms, they cannot be straightened to form filaments (e.g., through stabilization by cofilin), which makes them less susceptible to neutralization by the host cell. Full article

(This article belongs to the Special Issue Cytoskeletoxins: Bacterial and Viral Effector Proteins Targeting the Cytoskeleton)

► Show Figures

Graphical abstract

25 pages, 13306 KiB

Open AccessArticle

Beyond Microcystins: Cyanobacterial Extracts Induce Cytoskeletal Alterations in Rice Root Cells

by Dimitris Pappas, Manthos Panou, Ioannis-Dimosthenis S. Adamakis, Spyros Gkelis and Emmanuel Panteris

Int. J. Mol. Sci. 2020, 21(24), 9649; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21249649 - 17 Dec 2020

Cited by 10 | Viewed by 2525

Abstract

Microcystins (MCs) are cyanobacterial toxins and potent inhibitors of protein phosphatases 1 (PP1) and 2A (PP2A), which are involved in plant cytoskeleton (microtubules and F-actin) organization. Therefore, studies on the toxicity of cyanobacterial products on plant cells have so far been focused on MCs. In this study, we investigated the effects of extracts from 16 (4 MC-producing and 12 non-MC-producing) cyanobacterial strains from several habitats, on various enzymes (PP1, trypsin, elastase), on the plant cytoskeleton and H₂O₂ levels in Oryza sativa (rice) root cells. Seedling roots were treated for various time periods (1, 12, and 24 h) with aqueous cyanobacterial extracts and underwent either immunostaining for α-tubulin or staining of F-actin with fluorescent phalloidin. 2,7-dichlorofluorescein diacetate (DCF-DA) staining was performed for H₂O₂ imaging. The enzyme assays confirmed the bioactivity of the extracts of not only MC-rich (MC+), but also MC-devoid (MC−) extracts, which induced major time-dependent alterations on both components of the plant cytoskeleton. These findings suggest that a broad spectrum of bioactive cyanobacterial compounds, apart from MCs or other known cyanotoxins (such as cylindrospermopsin), can affect plants by disrupting the cytoskeleton. Full article

(This article belongs to the Special Issue Cytoskeletoxins: Bacterial and Viral Effector Proteins Targeting the Cytoskeleton)

► Show Figures

Figure 1

Review

Jump to: Research

48 pages, 2858 KiB

Open AccessReview

Manipulation of Focal Adhesion Signaling by Pathogenic Microbes

by Korinn N. Murphy and Amanda J. Brinkworth

Int. J. Mol. Sci. 2021, 22(3), 1358; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031358 - 29 Jan 2021

Cited by 10 | Viewed by 4786

Abstract

Focal adhesions (FAs) serve as dynamic signaling hubs within the cell. They connect intracellular actin to the extracellular matrix (ECM) and respond to environmental cues. In doing so, these structures facilitate important processes such as cell–ECM adhesion and migration. Pathogenic microbes often modify the host cell actin cytoskeleton in their pursuit of an ideal replicative niche or during invasion to facilitate uptake. As actin-interfacing structures, FA dynamics are also intimately tied to actin cytoskeletal organization. Indeed, exploitation of FAs is another avenue by which pathogenic microbes ensure their uptake, survival and dissemination. This is often achieved through the secretion of effector proteins which target specific protein components within the FA. Molecular mimicry of the leucine–aspartic acid (LD) motif or vinculin-binding domains (VBDs) commonly found within FA proteins is a common microbial strategy. Other effectors may induce post-translational modifications to FA proteins through the regulation of phosphorylation sites or proteolytic cleavage. In this review, we present an overview of the regulatory mechanisms governing host cell FAs, and provide examples of how pathogenic microbes have evolved to co-opt them to their own advantage. Recent technological advances pose exciting opportunities for delving deeper into the mechanistic details by which pathogenic microbes modify FAs. Full article

(This article belongs to the Special Issue Cytoskeletoxins: Bacterial and Viral Effector Proteins Targeting the Cytoskeleton)

► Show Figures

Figure 1

32 pages, 3123 KiB

Open AccessReview

Staying out or Going in? The Interplay between Type 3 and Type 5 Secretion Systems in Adhesion and Invasion of Enterobacterial Pathogens

by Rachel Whelan, Gareth McVicker and Jack C. Leo

Int. J. Mol. Sci. 2020, 21(11), 4102; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21114102 - 08 Jun 2020

Cited by 8 | Viewed by 6039

Abstract

Enteric pathogens rely on a variety of toxins, adhesins and other virulence factors to cause infections. Some of the best studied pathogens belong to the Enterobacterales order; these include enteropathogenic and enterohemorrhagic Escherichia coli, Shigella spp., and the enteropathogenic Yersiniae. The pathogenesis of these organisms involves two different secretion systems, a type 3 secretion system (T3SS) and type 5 secretion systems (T5SSs). The T3SS forms a syringe-like structure spanning both bacterial membranes and the host cell plasma membrane that translocates toxic effector proteins into the cytoplasm of the host cell. T5SSs are also known as autotransporters, and they export part of their own polypeptide to the bacterial cell surface where it exerts its function, such as adhesion to host cell receptors. During infection with these enteropathogens, the T3SS and T5SS act in concert to bring about rearrangements of the host cell cytoskeleton, either to invade the cell, confer intracellular motility, evade phagocytosis or produce novel structures to shelter the bacteria. Thus, in these bacteria, not only the T3SS effectors but also T5SS proteins could be considered “cytoskeletoxins” that bring about profound alterations in host cell cytoskeletal dynamics and lead to pathogenic outcomes. Full article

(This article belongs to the Special Issue Cytoskeletoxins: Bacterial and Viral Effector Proteins Targeting the Cytoskeleton)

► Show Figures