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      Exploring Virulence Factors and Alternative Therapies against Staphylococcus aureus Pneumonia

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          Abstract

          Pneumonia is an acute pulmonary infection associated with high mortality and an immense financial burden on healthcare systems. Staphylococcus aureus is an opportunistic pathogen capable of inducing S. aureus pneumonia (SAP), with some lineages also showing multidrug resistance. Given the high level of antibiotic resistance, much research has been focused on targeting S. aureus virulence factors, including toxins and biofilm-associated proteins, in an attempt to develop effective SAP therapeutics. Despite several promising leads, many hurdles still remain for S. aureus vaccine research. Here, we review the state-of-the-art SAP therapeutics, highlight their pitfalls, and discuss alternative approaches of potential significance and future perspectives.

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          Most cited references222

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          Microorganisms that invade a vertebrate host are initially recognized by the innate immune system through germline-encoded pattern-recognition receptors (PRRs). Several classes of PRRs, including Toll-like receptors and cytoplasmic receptors, recognize distinct microbial components and directly activate immune cells. Exposure of immune cells to the ligands of these receptors activates intracellular signaling cascades that rapidly induce the expression of a variety of overlapping and unique genes involved in the inflammatory and immune responses. New insights into innate immunity are changing the way we think about pathogenesis and the treatment of infectious diseases, allergy, and autoimmunity.
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            Bacterial biofilms: a common cause of persistent infections.

            Bacteria that attach to surfaces aggregate in a hydrated polymeric matrix of their own synthesis to form biofilms. Formation of these sessile communities and their inherent resistance to antimicrobial agents are at the root of many persistent and chronic bacterial infections. Studies of biofilms have revealed differentiated, structured groups of cells with community properties. Recent advances in our understanding of the genetic and molecular basis of bacterial community behavior point to therapeutic targets that may provide a means for the control of biofilm infections.
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              Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society.

              It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.These guidelines are intended for use by healthcare professionals who care for patients at risk for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), including specialists in infectious diseases, pulmonary diseases, critical care, and surgeons, anesthesiologists, hospitalists, and any clinicians and healthcare providers caring for hospitalized patients with nosocomial pneumonia. The panel's recommendations for the diagnosis and treatment of HAP and VAP are based upon evidence derived from topic-specific systematic literature reviews.
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                Author and article information

                Journal
                Toxins (Basel)
                Toxins (Basel)
                toxins
                Toxins
                MDPI
                2072-6651
                18 November 2020
                November 2020
                : 12
                : 11
                : 721
                Affiliations
                [1 ]Laboratory of Medical Microbiology, Vaccine and Infectious Diseases Institute, University of Antwerp, 2610 Antwerp, Belgium; Jelle.Vlaeminck@ 123456uantwerpen.be (J.V.); leen.timbermont@ 123456uantwerpen.be (L.T.)
                [2 ]Department of Immunology, Institute of Immunology and Transfusion Medicine, University Medicine Greifswald, 17475 Greifswald, Germany; dina.raafat@ 123456med.uni-greifswald.de (D.R.); Nicole.Normann@ 123456med.uni-greifswald.de (N.N.)
                [3 ]Department of Microbiology and Immunology, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt
                [4 ]Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, 17475 Greifswald, Germany; kristin.surmann@ 123456uni-greifswald.de
                [5 ]Microbiome Discovery, Microbial Sciences, BioPharmaceuticals R & D, AstraZeneca, Gaithersburg, MD 20878, USA; bret.sellman@ 123456astrazeneca.com
                [6 ]Department of Medical Microbiology and Infectious Diseases, Erasmus Medical Center Rotterdam, 3015 Rotterdam, The Netherlands; w.vanwamel@ 123456erasmusmc.nl
                Author notes
                [* ]Correspondence: surbhi.malhotra@ 123456uantwerpen.be ; Tel.: +32-3-265-27-52
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-3610-9863
                https://orcid.org/0000-0002-9543-9205
                https://orcid.org/0000-0001-6267-6450
                Article
                toxins-12-00721
                10.3390/toxins12110721
                7698915
                33218049
                b157150e-485d-4b90-b8cb-6af3d9d6b0a1
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 19 October 2020
                : 15 November 2020
                Categories
                Review

                Molecular medicine
                staphylococcus aureus,pneumonia,virulence,therapeutics
                Molecular medicine
                staphylococcus aureus, pneumonia, virulence, therapeutics

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