Staphylococcus aureus Toxins

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

Deadline for manuscript submissions: closed (30 April 2019) | Viewed by 85436

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editor


E-Mail Website
Guest Editor
Department of Microbiology, University of Wisconsin-La Crosse, 1725 State St., La Crosse, WI 54601, USA
Interests: drug discovery; anti-staphylococcal drugs; bacterial pathogenesis; two-component systems; uropathogenic Escherichia coli
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Staphylococcus aureus toxins have a significant role to play in S. aureus pathogenesis.  Toxins cause direct damage to the host and some toxins (e.g., enterotoxins and toxic shock syndrome toxin) and elicit a massive pro-inflammatory response that will contribute to indirect damage to the host. Although we know a lot about these S. aureus toxins, we still have a lot to learn about the molecular pathogenesis of them and how the genes that encode the toxins are regulated. This Special Issue will focus on how the toxins play a role in S. aureus pathogenesis, what regulatory mechanisms affect expression of the toxins, and current research tied to the development of toxoid-based vaccines to prevent S. aureus infections.

Prof. William R. Schwan
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 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 2700 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

  • Staphylococcus aureus
  • toxin
  • regulation
  • pathogenesis
  • mechanism of action

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue polices can be found here.

Published Papers (13 papers)

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

Editorial

Jump to: Research, Review

3 pages, 197 KiB  
Editorial
Staphylococcus aureus Toxins: Armaments for a Significant Pathogen
by William R. Schwan
Toxins 2019, 11(8), 457; https://doi.org/10.3390/toxins11080457 - 3 Aug 2019
Cited by 9 | Viewed by 4218
Abstract
Staphylococcus species are common inhabitants of humans and other animals [...] Full article
(This article belongs to the Special Issue Staphylococcus aureus Toxins)

Research

Jump to: Editorial, Review

15 pages, 1438 KiB  
Article
Regulation of the Staphylococcal Superantigen-Like Protein 1 Gene of Community-Associated Methicillin-Resistant Staphylococcus aureus in Murine Abscesses
by Daniel J. Bretl, Abdulaziz Elfessi, Hannah Watkins and William R. Schwan
Toxins 2019, 11(7), 391; https://doi.org/10.3390/toxins11070391 - 4 Jul 2019
Cited by 6 | Viewed by 3392
Abstract
Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) causes substantial skin and soft tissue infections annually in the United States and expresses numerous virulence factors, including a family of toxins known as the staphylococcal superantigen-like (SSL) proteins. Many of the SSL protein structures have been determined [...] Read more.
Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) causes substantial skin and soft tissue infections annually in the United States and expresses numerous virulence factors, including a family of toxins known as the staphylococcal superantigen-like (SSL) proteins. Many of the SSL protein structures have been determined and implicated in immune system avoidance, but the full scope that these proteins play in different infection contexts remains unknown and continues to warrant investigation. Analysis of ssl gene regulation may provide valuable information related to the function of these proteins. To determine the transcriptional regulation of the ssl1 gene of CA-MRSA strain MW2, an ssl1 promoter::lux fusion was constructed and transformed into S. aureus strains RN6390 and Newman. Resulting strains were grown in a defined minimal medium (DSM) broth and nutrient-rich brain-heart infusion (BHI) broth and expression was determined by luminescence. Transcription of ssl1 was up-regulated and occurred earlier during growth in DSM broth compared to BHI broth suggesting expression is regulated by nutrient availability. RN6390 and Newman strains containing the ssl1::lux fusion were also used to analyze regulation in vivo using a mouse abscess model of infection. A marked increase in ssl1 transcription occurred early during infection, suggesting SSL1 is important during early stages of infection, perhaps to avoid the immune system. Full article
(This article belongs to the Special Issue Staphylococcus aureus Toxins)
Show Figures

Figure 1

22 pages, 2308 KiB  
Article
Novel Regulation of Alpha-Toxin and the Phenol-Soluble Modulins by Peptidyl-Prolyl cis/trans Isomerase Enzymes in Staphylococcus aureus
by Rebecca A. Keogh, Rachel L. Zapf, Emily Trzeciak, Gillian G. Null, Richard E. Wiemels and Ronan K. Carroll
Toxins 2019, 11(6), 343; https://doi.org/10.3390/toxins11060343 - 16 Jun 2019
Cited by 11 | Viewed by 5995
Abstract
Peptidyl-prolyl cis/trans isomerases (PPIases) are enzymes that catalyze the cis-to-trans isomerization around proline bonds, allowing proteins to fold into their correct confirmation. Previously, we identified two PPIase enzymes in Staphylococcus aureus (PpiB and PrsA) that are involved in the regulation of [...] Read more.
Peptidyl-prolyl cis/trans isomerases (PPIases) are enzymes that catalyze the cis-to-trans isomerization around proline bonds, allowing proteins to fold into their correct confirmation. Previously, we identified two PPIase enzymes in Staphylococcus aureus (PpiB and PrsA) that are involved in the regulation of virulence determinants and have shown that PpiB contributes to S. aureus virulence in a murine abscess model of infection. Here, we further examine the role of these PPIases in S. aureus virulence and, in particular, their regulation of hemolytic toxins. Using murine abscess and systemic models of infection, we show that a ppiB mutant in a USA300 background is attenuated for virulence but that a prsA mutant is not. Deletion of the ppiB gene leads to decreased bacterial survival in macrophages and nasal epithelial cells, while there is no significant difference when prsA is deleted. Analysis of culture supernatants reveals that a ppiB mutant strain has reduced levels of the phenol-soluble modulins and that both ppiB and prsA mutants have reduced alpha-toxin activity. Finally, we perform immunoprecipitation to identify cellular targets of PpiB and PrsA. Results suggest a novel role for PpiB in S. aureus protein secretion. Collectively, our results demonstrate that PpiB and PrsA influence S. aureus toxins via distinct mechanisms, and that PpiB but not PrsA contributes to disease. Full article
(This article belongs to the Special Issue Staphylococcus aureus Toxins)
Show Figures

Graphical abstract

21 pages, 3599 KiB  
Article
Rational Design of Toxoid Vaccine Candidates for Staphylococcus aureus Leukocidin AB (LukAB)
by Shweta Kailasan, Thomas Kort, Ipsita Mukherjee, Grant C. Liao, Tulasikumari Kanipakala, Nils Williston, Nader Ganjbaksh, Arundhathi Venkatasubramaniam, Frederick W. Holtsberg, Hatice Karauzum, Rajan P. Adhikari and M. Javad Aman
Toxins 2019, 11(6), 339; https://doi.org/10.3390/toxins11060339 - 14 Jun 2019
Cited by 15 | Viewed by 5033
Abstract
Staphylococcus aureus (SA) infections cause high mortality and morbidity in humans. Being central to its pathogenesis, S. aureus thwarts the host defense by secreting a myriad of virulence factors, including bicomponent, pore-forming leukotoxins. While all vaccine development efforts that aimed at achieving opsonophagocytic [...] Read more.
Staphylococcus aureus (SA) infections cause high mortality and morbidity in humans. Being central to its pathogenesis, S. aureus thwarts the host defense by secreting a myriad of virulence factors, including bicomponent, pore-forming leukotoxins. While all vaccine development efforts that aimed at achieving opsonophagocytic killing have failed, targeting virulence by toxoid vaccines represents a novel approach to preventing mortality and morbidity that are caused by SA. The recently discovered leukotoxin LukAB kills human phagocytes and monocytes and it is present in all known S. aureus clinical isolates. While using a structure-guided approach, we generated a library of mutations that targeted functional domains within the LukAB heterodimer to identify attenuated toxoids as potential vaccine candidates. The mutants were evaluated based on expression, solubility, yield, biophysical properties, cytotoxicity, and immunogenicity, and several fully attenuated LukAB toxoids that were capable of eliciting high neutralizing antibody titers were identified. Rabbit polyclonal antibodies against the lead toxoid candidate provided potent neutralization of LukAB. While the neutralization of LukAB alone was not sufficient to fully suppress leukotoxicity in supernatants of S. aureus USA300 isolates, a combination of antibodies against LukAB, α-toxin, and Panton-Valentine leukocidin completely neutralized the cytotoxicity of these strains. These data strongly support the inclusion of LukAB toxoids in a multivalent toxoid vaccine for the prevention of S. aureus disease. Full article
(This article belongs to the Special Issue Staphylococcus aureus Toxins)
Show Figures

Figure 1

12 pages, 2734 KiB  
Article
A Derivative of Butyric Acid, the Fermentation Metabolite of Staphylococcus epidermidis, Inhibits the Growth of a Staphylococcus aureus Strain Isolated from Atopic Dermatitis Patients
by Supitchaya Traisaeng, Deron Raymond Herr, Hsin-Jou Kao, Tsung-Hsien Chuang and Chun-Ming Huang
Toxins 2019, 11(6), 311; https://doi.org/10.3390/toxins11060311 - 31 May 2019
Cited by 45 | Viewed by 6083
Abstract
The microbiome is a rich source of metabolites for the development of novel drugs. Butyric acid, for example, is a short-chain fatty acid fermentation metabolite of the skin probiotic bacterium Staphylococcus epidermidis (S. epidermidis). Glycerol fermentation of S. epidermidis resulted in [...] Read more.
The microbiome is a rich source of metabolites for the development of novel drugs. Butyric acid, for example, is a short-chain fatty acid fermentation metabolite of the skin probiotic bacterium Staphylococcus epidermidis (S. epidermidis). Glycerol fermentation of S. epidermidis resulted in the production of butyric acid and effectively hindered the growth of a Staphylococcus aureus (S. aureus) strain isolated from skin lesions of patients with atopic dermatitis (AD) in vitro and in vivo. This approach, however, is unlikely to be therapeutically useful since butyric acid is malodorous and requires a high concentration in the mM range for growth suppression of AD S. aureus. A derivative of butyric acid, BA–NH–NH–BA, was synthesized by conjugation of two butyric acids to both ends of an –NH–O–NH– linker. BA–NH–NH–BA significantly lowered the concentration of butyric acid required to inhibit the growth of AD S. aureus. Like butyric acid, BA–NH–NH–BA functioned as a histone deacetylase (HDAC) inhibitor by inducing the acetylation of Histone H3 lysine 9 (AcH3K9) in human keratinocytes. Furthermore, BA–NH–NH–BA ameliorated AD S. aureus-induced production of pro-inflammatory interleukin (IL)-6 and remarkably reduced the colonization of AD S. aureus in mouse skin. These results describe a novel derivative of a skin microbiome fermentation metabolite that exhibits anti-inflammatory and S. aureus bactericidal activity. Full article
(This article belongs to the Special Issue Staphylococcus aureus Toxins)
Show Figures

Figure 1

11 pages, 1262 KiB  
Communication
Study on the Growth and Enterotoxin Production by Staphylococcus aureus in Canned Meat before Retorting
by Luca Grispoldi, Paul Alexanderu Popescu, Musafiri Karama, Vito Gullo, Giusi Poerio, Elena Borgogni, Paolo Torlai, Giuseppina Chianese, Anna Giovanna Fermani, Paola Sechi and Beniamino Cenci-Goga
Toxins 2019, 11(5), 291; https://doi.org/10.3390/toxins11050291 - 23 May 2019
Cited by 24 | Viewed by 6190
Abstract
Possible contamination by Staphylococcus aureus of the production environment and of the meat of a canned meat production factory was analysed. A total of 108 samples were taken from nine critical control points, 13 of them were positive for S. aureus. [...] Read more.
Possible contamination by Staphylococcus aureus of the production environment and of the meat of a canned meat production factory was analysed. A total of 108 samples were taken from nine critical control points, 13 of them were positive for S. aureus. None of the isolates produced enterotoxins. To determine how much time can elapse between can seaming and sterilisation in the autoclave without any risk of enterotoxin production by S. aureus, the growth and enterotoxin production of three enterotoxin A producing strains of S. aureus (one ATCC strain and two field strains) in canned meat before sterilisation was investigated at three different temperatures (37, 20 and 10 °C). Two types of meat were used, one with and one without sodium nitrite. In the canned products, the spiked bacteria spread throughout the meat and reached high levels. Enterotoxin production was shown to start 10 hours after incubation at 37 °C and after 48 h after incubation at 20 °C; the production of enterotoxin was always detected in the transition between the exponential and the stationary growth phase. At 10 °C, the enterotoxin was never detected. The statistical analysis of the data showed that the difference between the two different types of meat was not statistically significant (p value > 0.05). Since it is well known that following heat treatment, staphylococcal enterotoxins, although still active (in in vivo assays), can be undetectable (loss of serological recognition) depending on the food matrix and pH, it is quite difficult to foresee the impact of heat treatment on enterotoxin activity. Therefore, although the bacteria are eliminated, the toxins may remain and cause food poisoning. The significance of the results of this study towards implementing good manufacturing practices and hazard analysis critical control points in a canned meat factory are discussed with reference to the management of pre-retorting steps after seaming. Full article
(This article belongs to the Special Issue Staphylococcus aureus Toxins)
Show Figures

Figure 1

13 pages, 2662 KiB  
Article
Staphylococcal Enterotoxin C Is an Important Virulence Factor for Mastitis
by Rendong Fang, Jingchun Cui, Tengteng Cui, Haiyong Guo, Hisaya K. Ono, Chun-Ho Park, Masashi Okamura, Akio Nakane and Dong-Liang Hu
Toxins 2019, 11(3), 141; https://doi.org/10.3390/toxins11030141 - 2 Mar 2019
Cited by 27 | Viewed by 5148
Abstract
Staphylococcus aureus is an important bacterial pathogen causing bovine mastitis, but little is known about the virulence factor and the inflammatory responses in the mammary infection. Staphylococcal enterotoxin C (SEC) is the most frequent toxin produced by S. aureus, isolated from bovine [...] Read more.
Staphylococcus aureus is an important bacterial pathogen causing bovine mastitis, but little is known about the virulence factor and the inflammatory responses in the mammary infection. Staphylococcal enterotoxin C (SEC) is the most frequent toxin produced by S. aureus, isolated from bovine mastitis. To investigate the pathogenic activity of SEC in the inflammation of the mammary gland and the immune responses in an animal model, mouse mammary glands were injected with SEC, and the clinical signs, inflammatory cell infiltration, and proinflammatory cytokine production in the mammary glands were assessed. SEC induced significant inflammatory reactions in the mammary gland, in a dose-dependent manner. SEC-injected mammary glands showed a severe inflammation with inflammatory cell infiltration and tissue damage. In addition, interleukin (IL)-1β and IL-6 production in the SEC-injected mammary glands were significantly higher than those in the PBS control glands. Furthermore, the SEC-induced inflammation and tissue damage in the mammary gland were specifically inhibited by anti-SEC antibody. These results indicated, for the first time, that SEC can directly cause inflammation, proinflammatory cytokine production, and tissue damage in mammary glands, suggesting that SEC might play an important role in the development of mastitis associated with S. aureus infection. This finding offers an opportunity to develop novel treatment strategies for reduction of mammary tissue damage in mastitis. Full article
(This article belongs to the Special Issue Staphylococcus aureus Toxins)
Show Figures

Figure 1

15 pages, 2444 KiB  
Article
Clinical S. aureus Isolates Vary in Their Virulence to Promote Adaptation to the Host
by Lorena Tuchscherr, Christine Pöllath, Anke Siegmund, Stefanie Deinhardt-Emmer, Verena Hoerr, Carl-Magnus Svensson, Marc Thilo Figge, Stefan Monecke and Bettina Löffler
Toxins 2019, 11(3), 135; https://doi.org/10.3390/toxins11030135 - 1 Mar 2019
Cited by 36 | Viewed by 5377
Abstract
Staphylococcus aureus colonizes epithelial surfaces, but it can also cause severe infections. The aim of this work was to investigate whether bacterial virulence correlates with defined types of tissue infections. For this, we collected 10–12 clinical S. aureus strains each from nasal colonization, [...] Read more.
Staphylococcus aureus colonizes epithelial surfaces, but it can also cause severe infections. The aim of this work was to investigate whether bacterial virulence correlates with defined types of tissue infections. For this, we collected 10–12 clinical S. aureus strains each from nasal colonization, and from patients with endoprosthesis infection, hematogenous osteomyelitis, and sepsis. All strains were characterized by genotypic analysis, and by the expression of virulence factors. The host–pathogen interaction was studied through several functional assays in osteoblast cultures. Additionally, selected strains were tested in a murine sepsis/osteomyelitis model. We did not find characteristic bacterial features for the defined infection types; rather, a wide range in all strain collections regarding cytotoxicity and invasiveness was observed. Interestingly, all strains were able to persist and to form small colony variants (SCVs). However, the low-cytotoxicity strains survived in higher numbers, and were less efficiently cleared by the host than the highly cytotoxic strains. In summary, our results indicate that not only destructive, but also low-cytotoxicity strains are able to induce infections. The low-cytotoxicity strains can successfully survive, and are less efficiently cleared from the host than the highly cytotoxic strains, which represent a source for chronic infections. The understanding of this interplay/evolution between the host and the pathogen during infection, with specific attention towards low-cytotoxicity isolates, will help to optimize treatment strategies for invasive and therapy-refractory infection courses. Full article
(This article belongs to the Special Issue Staphylococcus aureus Toxins)
Show Figures

Figure 1

13 pages, 10387 KiB  
Article
Sphingomyelin Depletion from Plasma Membranes of Human Airway Epithelial Cells Completely Abrogates the Deleterious Actions of S. aureus Alpha-Toxin
by Sabine Ziesemer, Nils Möller, Andreas Nitsch, Christian Müller, Achim G. Beule and Jan-Peter Hildebrandt
Toxins 2019, 11(2), 126; https://doi.org/10.3390/toxins11020126 - 20 Feb 2019
Cited by 11 | Viewed by 3919
Abstract
Interaction of Staphylococcus aureus alpha-toxin (hemolysin A, Hla) with eukaryotic cell membranes is mediated by proteinaceous receptors and certain lipid domains in host cell plasma membranes. Hla is secreted as a 33 kDa monomer that forms heptameric transmembrane pores whose action compromises maintenance [...] Read more.
Interaction of Staphylococcus aureus alpha-toxin (hemolysin A, Hla) with eukaryotic cell membranes is mediated by proteinaceous receptors and certain lipid domains in host cell plasma membranes. Hla is secreted as a 33 kDa monomer that forms heptameric transmembrane pores whose action compromises maintenance of cell shape and epithelial tightness. It is not exactly known whether certain membrane lipid domains of host cells facilitate adhesion of Ha monomers, oligomerization, or pore formation. We used sphingomyelinase (hemolysin B, Hlb) expressed by some strains of staphylococci to pre-treat airway epithelial model cells in order to specifically decrease the sphingomyelin (SM) abundance in their plasma membranes. Such a pre-incubation exclusively removed SM from the plasma membrane lipid fraction. It abrogated the formation of heptamers and prevented the formation of functional transmembrane pores. Hla exposure of rHlb pre-treated cells did not result in increases in [Ca2+]i, did not induce any microscopically visible changes in cell shape or formation of paracellular gaps, and did not induce hypo-phosphorylation of the actin depolymerizing factor cofilin as usual. Removal of sphingomyelin from the plasma membranes of human airway epithelial cells completely abrogates the deleterious actions of Staphylococcus aureus alpha-toxin. Full article
(This article belongs to the Special Issue Staphylococcus aureus Toxins)
Show Figures

Figure 1

23 pages, 8876 KiB  
Communication
Bioinformatics and Functional Assessment of Toxin-Antitoxin Systems in Staphylococcus aureus
by Gul Habib, Qing Zhu and Baolin Sun
Toxins 2018, 10(11), 473; https://doi.org/10.3390/toxins10110473 - 14 Nov 2018
Cited by 19 | Viewed by 6665
Abstract
Staphylococcus aureus is a nosocomial pathogen that can cause chronic to persistent infections. Among different mediators of pathogenesis, toxin-antitoxin (TA) systems are emerging as the most prominent. These systems are frequently studied in Escherichia coli and Mycobacterial species but rarely explored in S. [...] Read more.
Staphylococcus aureus is a nosocomial pathogen that can cause chronic to persistent infections. Among different mediators of pathogenesis, toxin-antitoxin (TA) systems are emerging as the most prominent. These systems are frequently studied in Escherichia coli and Mycobacterial species but rarely explored in S. aureus. In the present study, we thoroughly analyzed the S. aureus genome and screened all possible TA systems using the Rasta bacteria and toxin-antitoxin database. We further searched E. coli and Mycobacterial TA homologs and selected 67 TA loci as putative TA systems in S. aureus. The host inhibition of growth (HigBA) TA family was predominantly detected in S. aureus. In addition, we detected seven pathogenicity islands in the S. aureus genome that are enriched with virulence genes and contain 26 out of 67 TA systems. We ectopically expressed multiple TA genes in E. coli and S. aureus that exhibited bacteriostatic and bactericidal effects on cell growth. The type I Fst toxin created holes in the cell wall while the TxpA toxin reduced cell size and induced cell wall septation. Besides, we identified a new TA system whose antitoxin functions as a transcriptional autoregulator while the toxin functions as an inhibitor of autoregulation. Altogether, this study provides a plethora of new as well as previously known TA systems that will revitalize the research on S. aureus TA systems. Full article
(This article belongs to the Special Issue Staphylococcus aureus Toxins)
Show Figures

Figure 1

14 pages, 2901 KiB  
Article
Erianin against Staphylococcus aureus Infection via Inhibiting Sortase A
by Ping Ouyang, Xuewen He, Zhong-Wei Yuan, Zhong-Qiong Yin, Hualin Fu, Juchun Lin, Changliang He, Xiaoxia Liang, Cheng Lv, Gang Shu, Zhi-Xiang Yuan, Xu Song, Lixia Li and Lizi Yin
Toxins 2018, 10(10), 385; https://doi.org/10.3390/toxins10100385 - 23 Sep 2018
Cited by 51 | Viewed by 6073
Abstract
With continuous emergence and widespread of multidrug-resistant Staphylococcus aureus infections, common antibiotics have become ineffective in treating these infections in the clinical setting. Anti-virulence strategies could be novel, effective therapeutic strategies against drug-resistant bacterial infections. Sortase A (srtA), a transpeptidase in gram-positive bacteria, [...] Read more.
With continuous emergence and widespread of multidrug-resistant Staphylococcus aureus infections, common antibiotics have become ineffective in treating these infections in the clinical setting. Anti-virulence strategies could be novel, effective therapeutic strategies against drug-resistant bacterial infections. Sortase A (srtA), a transpeptidase in gram-positive bacteria, can anchor surface proteins that play a vital role in pathogenesis of these bacteria. SrtA is known as a potential antivirulent drug target to treat bacterial infections. In this study, we found that erianin, a natural bibenzyl compound, could inhibit the activity of srtA in vitro (half maximal inhibitory concentration—IC50 = 20.91 ± 2.31 μg/mL, 65.7 ± 7.2 μM) at subminimum inhibitory concentrations (minimum inhibitory concentrations—MIC = 512 μg/mL against S. aureus). The molecular mechanism underlying the inhibition of srtA by erianin was identified using molecular dynamics simulation: erianin binds to srtA residues Ile182, Val193, Trp194, Arg197, and Ile199, forming a stable bond via hydrophobic interactions. In addition, the activities of S. aureus binding to fibronectin and biofilm formation were inhibited by erianin, when co-culture with S. aureus. In vivo, erianin could improve the survival in mice that infected with S. aureus by tail vein injection. Experimental results showed that erianin is a potential novel therapeutic compound against S. aureus infections via affecting srtA. Full article
(This article belongs to the Special Issue Staphylococcus aureus Toxins)
Show Figures

Figure 1

Review

Jump to: Editorial, Research

18 pages, 1461 KiB  
Review
An Eye on Staphylococcus aureus Toxins: Roles in Ocular Damage and Inflammation
by Roger Astley, Frederick C. Miller, Md Huzzatul Mursalin, Phillip S. Coburn and Michelle C. Callegan
Toxins 2019, 11(6), 356; https://doi.org/10.3390/toxins11060356 - 19 Jun 2019
Cited by 49 | Viewed by 15100
Abstract
Staphylococcus aureus (S. aureus) is a common pathogen of the eye, capable of infecting external tissues such as the tear duct, conjunctiva, and the cornea, as well the inner and more delicate anterior and posterior chambers. S. aureus produces numerous toxins and enzymes [...] Read more.
Staphylococcus aureus (S. aureus) is a common pathogen of the eye, capable of infecting external tissues such as the tear duct, conjunctiva, and the cornea, as well the inner and more delicate anterior and posterior chambers. S. aureus produces numerous toxins and enzymes capable of causing profound damage to tissues and organs, as well as modulating the immune response to these infections. Unfortunately, in the context of ocular infections, this can mean blindness for the patient. The role of α-toxin in corneal infection (keratitis) and infection of the interior of the eye (endophthalmitis) has been well established by comparing virulence in animal models and α-toxin-deficient isogenic mutants with their wild-type parental strains. The importance of other toxins, such as β-toxin, γ-toxin, and Panton–Valentine leukocidin (PVL), have been analyzed to a lesser degree and their roles in eye infections are less clear. Other toxins such as the phenol-soluble modulins have yet to be examined in any animal models for their contributions to virulence in eye infections. This review discusses the state of current knowledge of the roles of S. aureus toxins in eye infections and the controversies existing as a result of the use of different infection models. The strengths and limitations of these ocular infection models are discussed, as well as the need for physiological relevance in the study of staphylococcal toxins in these models. Full article
(This article belongs to the Special Issue Staphylococcus aureus Toxins)
Show Figures

Figure 1

13 pages, 857 KiB  
Review
Exploring the Role of Staphylococcus Aureus Toxins in Atopic Dermatitis
by Fabio Seiti Yamada Yoshikawa, Josenilson Feitosa de Lima, Maria Notomi Sato, Yasmin Álefe Leuzzi Ramos, Valeria Aoki and Raquel Leao Orfali
Toxins 2019, 11(6), 321; https://doi.org/10.3390/toxins11060321 - 5 Jun 2019
Cited by 46 | Viewed by 10953
Abstract
Atopic dermatitis (AD) is a chronic and inflammatory skin disease with intense pruritus and xerosis. AD pathogenesis is multifactorial, involving genetic, environmental, and immunological factors, including the participation of Staphylococcus aureus. This bacterium colonizes up to 30–100% of AD skin and its [...] Read more.
Atopic dermatitis (AD) is a chronic and inflammatory skin disease with intense pruritus and xerosis. AD pathogenesis is multifactorial, involving genetic, environmental, and immunological factors, including the participation of Staphylococcus aureus. This bacterium colonizes up to 30–100% of AD skin and its virulence factors are responsible for its pathogenicity and antimicrobial survival. This is a concise review of S. aureus superantigen-activated signaling pathways, highlighting their involvement in AD pathogenesis, with an emphasis on skin barrier disruption, innate and adaptive immunity dysfunction, and microbiome alterations. A better understanding of the combined mechanisms of AD pathogenesis may enhance the development of future targeted therapies for this complex disease. Full article
(This article belongs to the Special Issue Staphylococcus aureus Toxins)
Show Figures

Figure 1

Back to TopTop