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      Metamorphoses of Lyme disease spirochetes: phenomenon of Borrelia persisters

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          Abstract

          The survival of spirochetes from the Borrelia burgdorferi ( sensu lato) complex in a hostile environment is achieved by the regulation of differential gene expression in response to changes in temperature, salts, nutrient content, acidity fluctuation, multiple host or vector dependent factors, and leads to the formation of dormant subpopulations of cells. From the other side, alterations in the level of gene expression in response to antibiotic pressure leads to the establishment of a persisters subpopulation. Both subpopulations represent the cells in different physiological states. “Dormancy” and “persistence” do share some similarities, e.g. both represent cells with low metabolic activity that can exist for extended periods without replication, both constitute populations with different gene expression profiles and both differ significantly from replicating forms of spirochetes. Persisters are elusive, present in low numbers, morphologically heterogeneous, multi-drug-tolerant cells that can change with the environment. The definition of “persisters” substituted the originally-used term “survivors”, referring to the small bacterial population of Staphylococcus that survived killing by penicillin. The phenomenon of persisters is present in almost all bacterial species; however, the reasons why Borrelia persisters form are poorly understood. Persisters can adopt varying sizes and shapes, changing from well-known forms to altered morphologies. They are capable of forming round bodies, L-form bacteria, microcolonies or biofilms-like aggregates, which remarkably change the response of Borrelia to hostile environments. Persisters remain viable despite aggressive antibiotic challenge and are able to reversibly convert into motile forms in a favorable growth environment. Persisters are present in significant numbers in biofilms, which has led to the explanation of biofilm tolerance to antibiotics. Considering that biofilms are associated with numerous chronic diseases through their resilient presence in the human body, it is not surprising that interest in persisting cells has consequently accelerated. Certain diseases caused by pathogenic bacteria (e.g. tuberculosis, syphilis or leprosy) are commonly chronic in nature and often recur despite antibiotic treatment. Three decades of basic and clinical research have not yet provided a definite answer to the question: is there a connection between persisting spirochetes and recurrence of Lyme disease in patients?

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          Most cited references144

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          Microbial biofilms.

          Direct observations have clearly shown that biofilm bacteria predominate, numerically and metabolically, in virtually all nutrient-sufficient ecosystems. Therefore, these sessile organisms predominate in most of the environmental, industrial, and medical problems and processes of interest to microbiologists. If biofilm bacteria were simply planktonic cells that had adhered to a surface, this revelation would be unimportant, but they are demonstrably and profoundly different. We first noted that biofilm cells are at least 500 times more resistant to antibacterial agents. Now we have discovered that adhesion triggers the expression of a sigma factor that derepresses a large number of genes so that biofilm cells are clearly phenotypically distinct from their planktonic counterparts. Each biofilm bacterium lives in a customized microniche in a complex microbial community that has primitive homeostasis, a primitive circulatory system, and metabolic cooperativity, and each of these sessile cells reacts to its special environment so that it differs fundamentally from a planktonic cell of the same species.
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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

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                Author and article information

                Contributors
                natasha@paru.cas.cz
                marina@paru.cas.cz
                katerina.kybicova@szu.cz
                vancova@paru.cas.cz
                Journal
                Parasit Vectors
                Parasit Vectors
                Parasites & Vectors
                BioMed Central (London )
                1756-3305
                16 May 2019
                16 May 2019
                2019
                : 12
                : 237
                Affiliations
                [1 ]GRID grid.448361.c, Biology Centre CAS, Institute of Parasitology, ; Branisovska 31, 37005 Ceske Budejovice, Czech Republic
                [2 ]ISNI 0000 0001 2184 1595, GRID grid.425485.a, National Institute of Public Health, ; Srobarova 48, 100 42 Prague 10, Czech Republic
                Article
                3495
                10.1186/s13071-019-3495-7
                6521364
                31097026
                b82d7a20-db5f-4877-a202-3f417762f6a9
                © The Author(s) 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 14 February 2019
                : 9 May 2019
                Funding
                Funded by: Ministry of Education, Youth and Sport of the Czech Republic
                Award ID: CZ.02.1.01/0.0/0.0/16_013/0001775
                Award ID: LM2015062 Czech-BioImaging
                Funded by: Ministry of Health of the Czech Republic
                Award ID: NV19-05-00191
                Categories
                Review
                Custom metadata
                © The Author(s) 2019

                Parasitology
                borrelia burgdorferi,persisters,dormant forms,round bodies,biofilm,lyme disease,persistent infection,antibiotic treatment

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