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      The search for novel treatment strategies for Streptococcus pneumoniae infections

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          ABSTRACT

          This review provides an overview of the most important novel treatment strategies against Streptococcus pneumoniae infections published over the past 10 years. The pneumococcus causes the majority of community-acquired bacterial pneumonia cases, and it is one of the prime pathogens in bacterial meningitis. Over the last 10 years, extensive research has been conducted to prevent severe pneumococcal infections, with a major focus on (i) boosting the host immune system and (ii) discovering novel antibacterials. Boosting the immune system can be done in two ways, either by actively modulating host immunity, mostly through administration of selective antibodies, or by interfering with pneumococcal virulence factors, thereby supporting the host immune system to effectively overcome an infection. While several of such experimental therapies are promising, few have evolved to clinical trials. The discovery of novel antibacterials is hampered by the high research and development costs versus the relatively low revenues for the pharmaceutical industry. Nevertheless, novel enzymatic assays and target-based drug design, allow the identification of targets and the development of novel molecules to effectively treat this life-threatening pathogen.

          Abstract

          This review discusses recent progress in anti-pneumococcal treatment strategies, with a focus on novel drug targets.

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          Most cited references273

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          Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America

          Background: This document provides evidence-based clinical practice guidelines on the management of adult patients with community-acquired pneumonia. Methods: A multidisciplinary panel conducted pragmatic systematic reviews of the relevant research and applied Grading of Recommendations, Assessment, Development, and Evaluation methodology for clinical recommendations. Results: The panel addressed 16 specific areas for recommendations spanning questions of diagnostic testing, determination of site of care, selection of initial empiric antibiotic therapy, and subsequent management decisions. Although some recommendations remain unchanged from the 2007 guideline, the availability of results from new therapeutic trials and epidemiological investigations led to revised recommendations for empiric treatment strategies and additional management decisions. Conclusions: The panel formulated and provided the rationale for recommendations on selected diagnostic and treatment strategies for adult patients with community-acquired pneumonia.
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            Peptidoglycan structure and architecture.

            The peptidoglycan (murein) sacculus is a unique and essential structural element in the cell wall of most bacteria. Made of glycan strands cross-linked by short peptides, the sacculus forms a closed, bag-shaped structure surrounding the cytoplasmic membrane. There is a high diversity in the composition and sequence of the peptides in the peptidoglycan from different species. Furthermore, in several species examined, the fine structure of the peptidoglycan significantly varies with the growth conditions. Limited number of biophysical data on the thickness, elasticity and porosity of peptidoglycan are available. The different models for the architecture of peptidoglycan are discussed with respect to structural and physical parameters.
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              Polyvalent Interactions in Biological Systems: Implications for Design and Use of Multivalent Ligands and Inhibitors

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                Author and article information

                Contributors
                Journal
                FEMS Microbiol Rev
                FEMS Microbiol Rev
                femsre
                FEMS Microbiology Reviews
                Oxford University Press
                0168-6445
                1574-6976
                July 2021
                05 January 2021
                05 January 2021
                : 45
                : 4
                : fuaa072
                Affiliations
                Laboratory for Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp , Universiteitsplein 1, 2610 Wilrijk, Belgium
                Laboratory for Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp , Universiteitsplein 1, 2610 Wilrijk, Belgium
                Laboratory for Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp , Universiteitsplein 1, 2610 Wilrijk, Belgium
                Author notes
                Corresponding author: Laboratory for Microbiology, Parasitology and Hygiene, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium. Tel: +32 3 265 26 28; E-mail: paul.cos@ 123456uantwerpen.be
                Author information
                https://orcid.org/0000-0003-4361-8911
                Article
                fuaa072
                10.1093/femsre/fuaa072
                8371276
                33399826
                9a164d66-6a76-4733-a0e5-8b820902e45d
                © The Author(s) 2021. Published by Oxford University Press on behalf of FEMS.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 30 June 2020
                : 01 January 2021
                Page count
                Pages: 23
                Categories
                Review Article
                AcademicSubjects/SCI01150

                Microbiology & Virology
                streptococcus pneumoniae,virulence,drug development,novel drug targets,immunotherapy,antibiotics

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