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      Brucella – Virulence Factors, Pathogenesis and Treatment

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          Abstract

          Brucellae are Gram-negative, small rods infecting mammals and capable of causing disease called brucellosis. The infection results in abortion and sterility in domestic animals (sheeps, pigs, rams etc). Especially dangerous for humans are: Brucella melitensis, Brucella suis, Brucella abortus, and Brucella canis that trigger unspecific symptoms (flu-like manifestation). Brucella rods are introduced via host cells, by inhalation, skin abrasions, ingestion or mucosal membranes. The most important feature of Brucella is the ability to survive and multiply within both phagocytic and non-phagocytic cells. Brucella does not produce classical virulence factors: exotoxin, cytolisins, exoenzymes, plasmids, fimbria, and drug resistant forms. Major virulence factors are: lipopolysaccharide (LPS), T4SS secretion system and BvrR/BvrS system, which allow interaction with host cell surface, formation of an early, late BCV ( Brucella Containing Vacuole) and interaction with endoplasmic reticulum (ER) when the bacteria multiply. The treatment of brucellosis is based on two-drug therapy, the most common combinations of antibiotics are: doxycycline with rifampicin or fluoroquinolones with rifampicin. Currently, also other methods are used to disrupt Brucella intracellular replication (tauroursodeoxycholic acid or ginseng saponin fraction A).

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          Most cited references88

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          Human brucellosis.

          Human brucellosis still presents scientists and clinicians with several challenges, such as the understanding of pathogenic mechanisms of Brucella spp, the identification of markers for disease severity, progression, and treatment response, and the development of improved treatment regimens. Molecular studies have shed new light on the pathogenesis of Brucella spp, and new technologies have permitted the development of diagnostic tools that will be useful in developing countries, where brucellosis is still a very common but often neglected disease. However, further studies are needed to establish optimum treatment regimens and local and international control programmes. This Review summarises current knowledge of the pathogenic mechanisms, new diagnostic advances, therapeutic options, and the situation of developing countries in regard to human brucellosis.
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            Brucellosis: an overview.

            M Corbel (1997)
            Brucellosis remains a major zoonosis worldwide. Although many countries have eradicated Brucella abortus from cattle, in some areas Brucella melitensis has emerged as a cause of infection in this species as well as in sheep and goats. Despite vaccination campaigns with the Rev 1 strain, B. melitensis remains the principal cause of human brucellosis. Brucella suis is also emerging as an agent of infection in cattle, thus extending its opportunities to infect humans. The recent isolation of distinctive strains of Brucella from marine mammals has extended its ecologic range. Molecular genetic studies have demonstrated phylogenetic affiliation to Agrobacterium, Phyllobacterium, Ochrobactrum, and Rhizobium. Polymerase chain reaction and gene probe development may provide more effective typing methods. Pathogenicity is related to production of lipopolysaccharides containing a poly N-formyl perosamine O chain, CuZn superoxide dismutase, erythrlose phosphate dehydrogenase, stress-induced proteins related to intracellular survival, and adenine and guanine monophosphate inhibitors of phagocyte functions. Protective immunity is conferred by antibody to lipopolysaccharide and T-cell-mediated macrophage activation triggered by protein antigens. Diagnosis still centers on isolation of the organism and serologic test results, especially enzyme immunoassay, which is replacing other methods. Polymerase chain reaction is also under evaluation. Therapy is based on tetracyclines with or without rifampicin, aminoglycosides, or quinolones. No satisfactory vaccines against human brucellosis are available, although attenuated purE mutants appear promising.
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              The versatile bacterial type IV secretion systems.

              Bacteria use type IV secretion systems for two fundamental objectives related to pathogenesis--genetic exchange and the delivery of effector molecules to eukaryotic target cells. Whereas gene acquisition is an important adaptive mechanism that enables pathogens to cope with a changing environment during invasion of the host, interactions between effector and host molecules can suppress defence mechanisms, facilitate intracellular growth and even induce the synthesis of nutrients that are beneficial to bacterial colonization. Rapid progress has been made towards defining the structures and functions of type IV secretion machines, identifying the effector molecules, and elucidating the mechanisms by which the translocated effectors subvert eukaryotic cellular processes during infection.
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                Author and article information

                Journal
                Pol J Microbiol
                Pol. J. Microbiol
                PJM
                Polish Journal of Microbiology
                Exeley Inc.
                1733-1331
                2544-4646
                June 2018
                30 June 2018
                : 67
                : 2
                : 151-161
                Affiliations
                [1 ]Biological Threats Identification and Countermeasure Center of the General Karol Kaczkowski Military Institute of Hygiene and Epidemiology , Puławy, Poland
                [2 ]Lublin Medical University , Department of Didactics and Medical Simulation , Lublin, Poland
                Author notes
                * Corresponding author: P. Głowacka, Biological Threats Identification and Countermeasure Center of the General Karol Kaczkowski Military Institute of Hygiene and Epidemiology, Puławy, Poland; e-mail: ppaczka@ 123456wihe.pulawy.pl
                Article
                exeley
                10.21307/pjm-2018-029
                7256693
                30015453
                e5e9528a-f4fc-4c8d-b0ca-fcb75c46b822

                This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License ( https://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 17 October 2017
                : 21 December 2017
                : 28 February 2018
                Categories
                Microbiology

                brucella,endoplasmic reticulum,macrophage,replication,virulence factors

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