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      Staphylococcal Biofilms: Challenges and Novel Therapeutic Perspectives

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          Abstract

          Staphylococci, like Staphylococcus aureus and S. epidermidis, are common colonizers of the human microbiota. While being harmless in many cases, many virulence factors result in them being opportunistic pathogens and one of the major causes of hospital-acquired infections worldwide. One of these virulence factors is the ability to form biofilms—three-dimensional communities of microorganisms embedded in an extracellular polymeric matrix (EPS). The EPS is composed of polysaccharides, proteins and extracellular DNA, and is finely regulated in response to environmental conditions. This structured environment protects the embedded bacteria from the human immune system and decreases their susceptibility to antimicrobials, making infections caused by staphylococci particularly difficult to treat. With the rise of antibiotic-resistant staphylococci, together with difficulty in removing biofilms, there is a great need for new treatment strategies. The purpose of this review is to provide an overview of our current knowledge of the stages of biofilm development and what difficulties may arise when trying to eradicate staphylococcal biofilms. Furthermore, we look into promising targets and therapeutic methods, including bacteriocins and phage-derived antibiofilm approaches.

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          Quorum sensing: cell-to-cell communication in bacteria.

          Bacteria communicate with one another using chemical signal molecules. As in higher organisms, the information supplied by these molecules is critical for synchronizing the activities of large groups of cells. In bacteria, chemical communication involves producing, releasing, detecting, and responding to small hormone-like molecules termed autoinducers . This process, termed quorum sensing, allows bacteria to monitor the environment for other bacteria and to alter behavior on a population-wide scale in response to changes in the number and/or species present in a community. Most quorum-sensing-controlled processes are unproductive when undertaken by an individual bacterium acting alone but become beneficial when carried out simultaneously by a large number of cells. Thus, quorum sensing confuses the distinction between prokaryotes and eukaryotes because it enables bacteria to act as multicellular organisms. This review focuses on the architectures of bacterial chemical communication networks; how chemical information is integrated, processed, and transduced to control gene expression; how intra- and interspecies cell-cell communication is accomplished; and the intriguing possibility of prokaryote-eukaryote cross-communication.
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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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              Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European Economic Area in 2015: a population-level modelling analysis

              Summary Background Infections due to antibiotic-resistant bacteria are threatening modern health care. However, estimating their incidence, complications, and attributable mortality is challenging. We aimed to estimate the burden of infections caused by antibiotic-resistant bacteria of public health concern in countries of the EU and European Economic Area (EEA) in 2015, measured in number of cases, attributable deaths, and disability-adjusted life-years (DALYs). Methods We estimated the incidence of infections with 16 antibiotic resistance–bacterium combinations from European Antimicrobial Resistance Surveillance Network (EARS-Net) 2015 data that was country-corrected for population coverage. We multiplied the number of bloodstream infections (BSIs) by a conversion factor derived from the European Centre for Disease Prevention and Control point prevalence survey of health-care-associated infections in European acute care hospitals in 2011–12 to estimate the number of non-BSIs. We developed disease outcome models for five types of infection on the basis of systematic reviews of the literature. Findings From EARS-Net data collected between Jan 1, 2015, and Dec 31, 2015, we estimated 671 689 (95% uncertainty interval [UI] 583 148–763 966) infections with antibiotic-resistant bacteria, of which 63·5% (426 277 of 671 689) were associated with health care. These infections accounted for an estimated 33 110 (28 480–38 430) attributable deaths and 874 541 (768 837–989 068) DALYs. The burden for the EU and EEA was highest in infants (aged <1 year) and people aged 65 years or older, had increased since 2007, and was highest in Italy and Greece. Interpretation Our results present the health burden of five types of infection with antibiotic-resistant bacteria expressed, for the first time, in DALYs. The estimated burden of infections with antibiotic-resistant bacteria in the EU and EEA is substantial compared with that of other infectious diseases, and has increased since 2007. Our burden estimates provide useful information for public health decision-makers prioritising interventions for infectious diseases. Funding European Centre for Disease Prevention and Control.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Antibiotics (Basel)
                Antibiotics (Basel)
                antibiotics
                Antibiotics
                MDPI
                2079-6382
                29 January 2021
                February 2021
                : 10
                : 2
                : 131
                Affiliations
                [1 ]Faculty of Chemistry, Biotechnology and Food Science, The Norwegian University of Life Sciences, 1432 Ås, Norway; christian.kranjec@ 123456nmbu.no (C.K.); danae.morales.angeles@ 123456nmbu.no (D.M.A.); marita.torrissen.marli@ 123456nmbu.no (M.T.M.)
                [2 ]Department of Technology and Biotechnology of Dairy Products, Dairy Research Institute of Asturias (IPLA-CSIC), 33300 Villaviciosa, Spain; lucia.fernandez@ 123456ipla.csic.es (L.F.); pgarcia@ 123456ipla.csic.es (P.G.)
                [3 ]DairySafe Group, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain
                Author notes
                [* ]Correspondence: morten.kjos@ 123456nmbu.no (M.K.); dzung.diep@ 123456nmbu.no (D.B.D.)
                [†]

                These authors contributed equally.

                Author information
                https://orcid.org/0000-0001-9713-7406
                https://orcid.org/0000-0003-3749-1387
                https://orcid.org/0000-0003-1213-8165
                https://orcid.org/0000-0003-4448-9082
                Article
                antibiotics-10-00131
                10.3390/antibiotics10020131
                7911828
                33573022
                f3334ce6-e971-4465-a1e1-cabf9c50ae17
                © 2021 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
                : 05 January 2021
                : 27 January 2021
                Categories
                Review

                s. aureus,coagulase-negative staphylococci,biofilm,bacteriocins,bacteriophages,antibiotics

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