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      Kaempferol Inhibits the Primary Attachment Phase of Biofilm Formation in Staphylococcus aureus

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          Abstract

          The ability to form biofilms on surfaces makes Staphylococcus aureus the main pathogenic factor in implanted medical device infections. The aim of this study was to discover a biofilm inhibitor distinct from the antibiotics used to prevent infections resulting from S. aureus biofilms. Here, we describe kaempferol, a small molecule with anti-biofilm activity that specifically inhibited the formation of S. aureus biofilms. Crystal violet (CV) staining and fluorescence microscopy clearly showed that 64 μg/ml kaempferol inhibited biofilm formation by 80%. Meanwhile, the minimum inhibitory concentration (MIC) and growth curve results indicated that kaempferol had no antibacterial activity against the tested bacterial strain. Kaempferol inhibited the primary attachment phase of biofilm formation, as determined by a fibrinogen-binding assay. Moreover, a fluorescence resonance energy transfer (FRET) assay and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) analyses revealed that kaempferol reduced the activity of S. aureus sortaseA (SrtA) and the expression of adhesion-related genes. Based on these results, kaempferol provides a starting point for the development of novel anti-biofilm drugs, which may decrease the risk of bacterial drug resistance, to prevent S. aureus biofilm-related infections.

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          Most cited references52

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          Biofilm infections, their resilience to therapy and innovative treatment strategies.

          Biofilm formation of microorganisms causes persistent tissue and foreign body infections resistant to treatment with antimicrobial agents. Up to 80% of human bacterial infections are biofilm associated; such infections are most frequently caused by Staphylococcus epidermidis, Pseudomonas aeruginosa, Staphylococcus aureus and Enterobacteria such as Escherichia coli. The accurate diagnosis of biofilm infections is often difficult, which prevents the appropriate choice of treatment. As biofilm infections significantly contribute to patient morbidity and substantial healthcare costs, novel strategies to treat these infections are urgently required. Nucleotide second messengers, c-di-GMP, (p)ppGpp and potentially c-di-AMP, are major regulators of biofilm formation and associated antibiotic tolerance. Consequently, different components of these signalling networks might be appropriate targets for antibiofilm therapy in combination with antibiotic treatment strategies. In addition, cyclic di-nucleotides are microbial-associated molecular patterns with an almost universal presence. Their conserved structures sensed by the eukaryotic host have a widespread effect on the immune system. Thus, cyclic di-nucleotides are also potential immunotherapeutic agents to treat antibiotic-resistant bacterial infections. © 2012 The Association for the Publication of the Journal of Internal Medicine.
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            Staphylococcal biofilms.

            M. Otto (2008)
            Staphylococcus epidermidis and Staphylococcus aureus are the most frequent causes of nosocomial infections and infections on indwelling medical devices, which characteristically involve biofilms. Recent advances in staphylococcal molecular biology have provided more detailed insight into the basis of biofilm formation in these opportunistic pathogens. A series of surface proteins mediate initial attachment to host matrix proteins, which is followed by the expression of a cationic glucosamine-based exopolysaccharide that aggregates the bacterial cells. In some cases, proteins may function as alternative aggregating substances. Furthermore, surfactant peptides have now been recognized as key factors involved in generating the three-dimensional structure of a staphylococcal biofilm by cell-cell disruptive forces, which eventually may lead to the detachment of entire cell clusters. Transcriptional profiling experiments have defined the specific physiology of staphylococcal biofilms and demonstrated that biofilm resistance to antimicrobials is due to gene-regulated processes. Finally, novel animal models of staphylococcal biofilm-associated infection have given us important information on which factors define biofilm formation in vivo. These recent advances constitute an important basis for the development of anti-staphylococcal drugs and vaccines.
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              MSCRAMM-mediated adherence of microorganisms to host tissues.

              Microbial adhesion to host tissue is the initial critical event in the pathogenesis of most infections and, as such, is an attractive target for the development of new antimicrobial therapeutics. Specific microbial components (adhesins) mediate adherence to host tissues by participating in amazingly sophisticated interactions with host molecules. This review focuses on a class of cell surface adhesins that specifically interact with extracellular matrix components and which we have designated MSCRAMMs (microbial surface components recognizing adhesive matrix molecules). MSCRAMMs recognizing fibronectin-, fibrinogen-, collagen-, and heparin-related polysaccharides are discussed in terms of structural organization, ligand-binding structures, importance in host tissue colonization and invasion, and role as virulence factors.
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                Author and article information

                Contributors
                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                15 November 2017
                2017
                : 8
                : 2263
                Affiliations
                [1] 1College of Animal Science, Jilin University , Changchun, China
                [2] 2College of Animal Science and Technology, Jilin Agricultural University , Changchun, China
                [3] 3Department of Pharmacology, College of Basic Medical Science, Jilin University , Changchun, China
                [4] 4Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University , Changchun, China
                Author notes

                Edited by: Yuji Morita, Aichi Gakuin University, Japan

                Reviewed by: Emily E. Weinert, Emory University, United States; Fabian Davamani Amalraj, International Medical University, Malaysia; Sarah Rowe-Conlon, University of North Carolina at Chapel Hill, United States

                *Correspondence: Lin Wang wanglin1020@ 123456jlu.edu.cn

                This article was submitted to Antimicrobials, Resistance and Chemotherapy, a section of the journal Frontiers in Microbiology

                †These authors have contributed equally to this work.

                Article
                10.3389/fmicb.2017.02263
                5694784
                29187848
                00e05aea-ce38-4155-80e7-c857b834e780
                Copyright © 2017 Ming, Wang, Cao, Xiang, Mu, Cao, Li, Zhong, Dong, Zhong, Wang and Wang.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 23 May 2017
                : 02 November 2017
                Page count
                Figures: 5, Tables: 1, Equations: 0, References: 71, Pages: 11, Words: 7058
                Funding
                Funded by: The National Key Technology R&D Program
                Award ID: No. 2016YFD05013
                Categories
                Microbiology
                Original Research

                Microbiology & Virology
                staphylococcus aureus,biofilm,kaempferol,inhibitor,primary,adhesion
                Microbiology & Virology
                staphylococcus aureus, biofilm, kaempferol, inhibitor, primary, adhesion

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