Special Issue "Staphylococcus aureus Toxins: Promoter or Handicap during Infection"

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

Deadline for manuscript submissions: 30 June 2020.

Special Issue Editors

Dr. Lorena Tuchscherr
E-Mail Website
Guest Editor
Institute of Medical Microbiology, Jena University Hospital, Jena, Germany
Prof. Bettina Löffler
E-Mail Website
Guest Editor
Institute of Medical Microbiology, Jena University Hospital, Jena, Germany

Special Issue Information

Dear Colleagues,

S. aureus is an opportunistic and versatile pathogen that can cause several diseases ranging from acute and invasive to chronic and difficult-to-treat infections. S. aureus can colonize the nasopharynx of many individuals but also causes infections that vary from superficial mild skin infections to severe necrotizing diseases, such as bacteremia, infective endocarditis, osteomyelitis, and device-related infections. Many staphylococcal infections are associated with significant morbidity and mortality. The ability of S. aureus to trigger different types of infection is due to its wide repertoire of virulence factors and strategies that can evade the host immune system. To start the infection, S. aureus uses different surface-bound proteins that facilitate the pathogen to attach to host tissue and invade host cells. After internalization, S. aureus can express a multitude of molecules that destroy host cells in order to enter deep tissue structures and get the nutrition necessary for its growth or to defend against elements of the immune system, such as superantigens. However, for bacterial persistence, many of these toxins need to be downregulated. In this way, the bacteria can avoid clearance by the immune defense and can silently persist within host cells/tissue for long time periods.

Taken together, virulence factors, in particular toxins, need to be regulated precisely during the course of infection by global regulators which act as a feedback to the surrounding microenvironment. Even though staphylococcal toxins have been studied in depth, the question still remains as to whether a “virulent” strain which expresses a lot of secreted toxins or a “silent” persisting strain is the real danger for the host.

The purpose of this Special Issue is to publish original research work related to the role of toxins in immune escape and host–pathogen interaction, regulation of toxins during infection, relation between expression of virulence factors and clinical outcome, toxins as activators or inhibitors of host clearance machine, toxins as targets for vaccine development, and the impact of agr-negative strains in the clinic.

Dr. Lorena Tuchscherr
Prof. Bettina Löffler
Guest Editors

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

  • S. aureus
  • toxins
  • host–pathogen interaction
  • regulation
  • immune escape
  • host clearance evasion
  • persistence

Published Papers (3 papers)

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Research

Open AccessArticle
Host–Receptor Post-Translational Modifications Refine Staphylococcal Leukocidin Cytotoxicity
Toxins 2020, 12(2), 106; https://doi.org/10.3390/toxins12020106 - 06 Feb 2020
Abstract
Staphylococcal bi-component pore-forming toxins, also known as leukocidins, target and lyse human phagocytes in a receptor-dependent manner. S-components of the leukocidins Panton-Valentine leukocidin (PVL), γ-haemolysin AB (HlgAB) and CB (HlgCB), and leukocidin ED (LukED) specifically employ receptors that belong to the class of [...] Read more.
Staphylococcal bi-component pore-forming toxins, also known as leukocidins, target and lyse human phagocytes in a receptor-dependent manner. S-components of the leukocidins Panton-Valentine leukocidin (PVL), γ-haemolysin AB (HlgAB) and CB (HlgCB), and leukocidin ED (LukED) specifically employ receptors that belong to the class of G-protein coupled receptors (GPCRs). Although these receptors share a common structural architecture, little is known about the conserved characteristics of the interaction between leukocidins and GPCRs. In this study, we investigated host cellular pathways contributing to susceptibility towards S. aureus leukocidin cytotoxicity. We performed a genome-wide CRISPR/Cas9 library screen for toxin-resistance in U937 cells sensitized to leukocidins by ectopic expression of different GPCRs. Our screen identifies post-translational modification (PTM) pathways involved in the sulfation and sialylation of the leukocidin-receptors. Subsequent validation experiments show differences in the impact of PTM moieties on leukocidin toxicity, highlighting an additional layer of refinement and divergence in the staphylococcal host-pathogen interface. Leukocidin receptors may serve as targets for anti-staphylococcal interventions and understanding toxin-receptor interactions will facilitate the development of innovative therapeutics. Variations in the genes encoding PTM pathways could provide insight into observed differences in susceptibility of humans to infections with S. aureus. Full article
(This article belongs to the Special Issue Staphylococcus aureus Toxins: Promoter or Handicap during Infection)
Open AccessArticle
Modeling of Effective Antimicrobials to Reduce Staphylococcus aureus Virulence Gene Expression Using a Two-Compartment Hollow Fiber Infection Model
Toxins 2020, 12(2), 69; https://doi.org/10.3390/toxins12020069 (registering DOI) - 22 Jan 2020
Abstract
Toxins produced by community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) contribute to virulence. We developed a statistical approach to determine an optimum sequence of antimicrobials to treat CA-MRSA infections based on an antimicrobial’s ability to reduce virulence. In an in vitro pharmacodynamic hollow fiber model, [...] Read more.
Toxins produced by community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) contribute to virulence. We developed a statistical approach to determine an optimum sequence of antimicrobials to treat CA-MRSA infections based on an antimicrobial’s ability to reduce virulence. In an in vitro pharmacodynamic hollow fiber model, expression of six virulence genes (lukSF-PV, sek, seq, ssl8, ear, and lpl10) in CA-MRSA USA300 was measured by RT-PCR at six time points with or without human-simulated, pharmacokinetic dosing of five antimicrobials (clindamycin, minocycline, vancomycin, linezolid, and trimethoprim/sulfamethoxazole (SXT)). Statistical modeling identified the antimicrobial causing the greatest decrease in virulence gene expression at each time-point. The optimum sequence was SXT at T0 and T4, linezolid at T8, and clindamycin at T24–T72 when lukSF-PV was weighted as the most important gene or when all six genes were weighted equally. This changed to SXT at T0–T24, linezolid at T48, and clindamycin at T72 when lukSF-PV was weighted as unimportant. The empirical p-value for each optimum sequence according to the different weights was 0.001, 0.0009, and 0.0018 with 10,000 permutations, respectively, indicating statistical significance. A statistical method integrating data on change in gene expression upon multiple antimicrobial exposures is a promising tool for identifying a sequence of antimicrobials that is effective in sustaining reduced CA-MRSA virulence. Full article
(This article belongs to the Special Issue Staphylococcus aureus Toxins: Promoter or Handicap during Infection)
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Open AccessArticle
Staphylococcus aureus Pneumonia: Preceding Influenza Infection Paves the Way for Low-Virulent Strains
Toxins 2019, 11(12), 734; https://doi.org/10.3390/toxins11120734 - 17 Dec 2019
Abstract
Staphylococcus aureus is a facultative pathogenic bacterium that colonizes the nasopharyngeal area of healthy individuals, but can also induce severe infection, such as pneumonia. Pneumonia caused by mono- or superinfected S. aureus leads to high mortality rates. To establish an infection, S. aureus [...] Read more.
Staphylococcus aureus is a facultative pathogenic bacterium that colonizes the nasopharyngeal area of healthy individuals, but can also induce severe infection, such as pneumonia. Pneumonia caused by mono- or superinfected S. aureus leads to high mortality rates. To establish an infection, S. aureus disposes of a wide variety of virulence factors, which can vary between clinical isolates. Our study aimed to characterize pneumonia isolates for their virulent capacity. For this, we analyzed isolates from colonization, pneumonia due to S. aureus, and pneumonia due to S. aureus/influenza virus co-infection. A total of 70 strains were analyzed for their virulence genes and the host–pathogen interaction was analyzed through functional assays in cell culture systems. Strains from pneumonia due to S. aureus mono-infection showed enhanced invasion and cytotoxicity against professional phagocytes than colonizing and co-infecting strains. This corresponded to the high presence of cytotoxic components in pneumonia strains. By contrast, strains obtained from co-infection did not exhibit these virulence characteristics and resembled strains from colonization, although they caused the highest mortality rate in patients. Taken together, our results underline the requirement of invasion and toxins to cause pneumonia due to S. aureus mono-infection, whereas in co-infection even low-virulent strains can severely aggravate pneumonia. Full article
(This article belongs to the Special Issue Staphylococcus aureus Toxins: Promoter or Handicap during Infection)
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