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      Ecological fitness and strategies of adaptation of Bartonella species to their hosts and vectors☆

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          Abstract

          Bartonella spp. are facultative intracellular bacteria that cause characteristic host-restricted hemotropic infections in mammals and are typically transmitted by blood-sucking arthropods. In the mammalian reservoir, these bacteria initially infect a yet unrecognized primary niche, which seeds organisms into the blood stream leading to the establishment of a long-lasting intra-erythrocytic bacteremia as the hall-mark of infection. Bacterial type IV secretion systems, which are supra-molecular transporters ancestrally related to bacterial conjugation systems, represent crucial pathogenicity factors that have contributed to a radial expansion of the Bartonella lineage in nature by facilitating adaptation to unique mammalian hosts. On the molecular level, the type IV secretion system VirB/VirD4 is known to translocate a cocktail of different effector proteins into host cells, which subvert multiple cellular functions to the benefit of the infecting pathogen. Furthermore, bacterial adhesins mediate a critical, early step in the pathogenesis of the bartonellae by binding to extracellular matrix components of host cells, which leads to firm bacterial adhesion to the cell surface as a prerequisite for the efficient translocation of type IV secretion effector proteins. The best-studied adhesins in bartonellae are the orthologous trimeric autotransporter adhesins, BadA in Bartonella henselae and the Vomp family in Bartonella quintana. Genetic diversity and strain variability also appear to enhance the ability of bartonellae to invade not only specific reservoir hosts, but also accidental hosts, as shown for B. henselae. Bartonellae have been identified in many different blood-sucking arthropods, in which they are typically found to cause extracellular infections of the mid-gut epithelium. Adaptation to specific vectors and reservoirs seems to be a common strategy of bartonellae for transmission and host diversity. However, knowledge regarding arthropod specificity/restriction, the mode of transmission, and the bacterial factors involved in arthropod infection and transmission is still limited.

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          The ecology of infectious disease: effects of host diversity and community composition on Lyme disease risk.

          The extent to which the biodiversity and community composition of ecosystems affect their functions is an issue that grows ever more compelling as human impacts on ecosystems increase. We present evidence that supports a novel function of vertebrate biodiversity, the buffering of human risk of exposure to Lyme-disease-bearing ticks. We tested the Dilution Effect model, which predicts that high species diversity in the community of tick hosts reduces vector infection prevalence by diluting the effects of the most competent disease reservoir, the ubiquitous white-footed mouse (Peromyscus leucopus). As habitats are degraded by fragmentation or other anthropogenic forces, some members of the host community disappear. Thus, species-poor communities tend to have mice, but few other hosts, whereas species-rich communities have mice, plus many other potential hosts. We demonstrate that the most common nonmouse hosts are relatively poor reservoirs for the Lyme spirochete and should reduce the prevalence of the disease by feeding, but rarely infecting, ticks. By accounting for nearly every host species' contribution to the number of larval ticks fed and infected, we show that as new host species are added to a depauperate community, the nymphal infection prevalence, a key risk factor, declines. We identify important "dilution hosts" (e.g., squirrels), characterized by high tick burdens, low reservoir competence, and high population density, as well as "rescue hosts" (e.g., shrews), which are capable of maintaining high disease risk when mouse density is low. Our study suggests that the preservation of vertebrate biodiversity and community composition can reduce the incidence of Lyme disease.
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            Stimulation of TLR2 and TLR4 differentially skews the balance of T cells in a mouse model of arthritis.

            TLRs may contribute to the progression of rheumatoid arthritis through recognition of microbial or host-derived ligands found in arthritic joints. Here, we show that TLR2 and TLR4, but not TLR9, are involved in the pathogenesis of autoimmune arthritis and play distinct roles in the regulation of T cells and cytokines. We investigated the involvement of TLR2, TLR4, and TLR9 in the progression of arthritis using IL-1 receptor antagonist-knockout (IL1rn-/-) mice, which spontaneously develop an autoimmune T cell-mediated arthritis. Spontaneous onset of arthritis was dependent on TLR activation by microbial flora, as germ-free mice did not develop arthritis. Clinical and histopathological evaluation of IL1rn-/-Tlr2-/- mice revealed more severe arthritis, characterized by reduced suppressive function of Tregs and substantially increased IFN-gamma production by T cells. IL1rn-/-Tlr4-/- mice were, in contrast, protected against severe arthritis and had markedly lower numbers of Th17 cells and a reduced capacity to produce IL-17. A lack of Tlr9 did not affect the progression of arthritis. While any therapeutic intervention targeting TLR2 still seems complicated, the strict position of TLR4 upstream of a number of pathogenic cytokines including IL-17 provides an interesting potential therapeutic target for rheumatoid arthritis.
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              Biogenesis, architecture, and function of bacterial type IV secretion systems.

              Type IV secretion (T4S) systems are ancestrally related to bacterial conjugation machines. These systems assemble as a translocation channel, and often also as a surface filament or protein adhesin, at the envelopes of Gram-negative and Gram-positive bacteria. These organelles mediate the transfer of DNA and protein substrates to phylogenetically diverse prokaryotic and eukaryotic target cells. Many basic features of T4S are known, including structures of machine subunits, steps of machine assembly, substrates and substrate recognition mechanisms, and cellular consequences of substrate translocation. A recent advancement also has enabled definition of the translocation route for a DNA substrate through a T4S system of a Gram-negative bacterium. This review emphasizes the dynamics of assembly and function of model conjugation systems and the Agrobacterium tumefaciens VirB/D4 T4S system. We also summarize salient features of the increasingly studied effector translocator systems of mammalian pathogens.
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                Author and article information

                Journal
                Vet Res
                vetres
                Veterinary Research
                EDP Sciences
                0928-4249
                1297-9716
                Mar-Apr 2009
                14 March 2009
                14 March 2009
                : 40
                : 2 , Adaptative strategies of vector-borne pathogens to vectorial transmission ( publisher-idID: vetres/2009/02 )
                : 29
                Affiliations
                [1 ]simpleDepartment of Population Health and Reproduction, School of Veterinary Medicine, University of California , Davis, CA 95616, USA
                [2 ]simpleUMR BIPAR ENVA/AFSSA/INRA/UPVM, École Nationale Vétérinaire d’Alfort , 7 avenue du Général de Gaulle, 94704 Maisons-Alfort, France
                [3 ]simpleCenter for Comparative Medicine and Transitional Research, College of Veterinary Medicine, North Carolina State University , 4700 Hillsborough St., Raleigh, NC 27606, USA
                [4 ]simpleDepartment of Veterinary Pathology, Faculty of Veterinary Science, University of Liverpool , Leahurst, CH64 7TE, United Kingdom
                [5 ]simpleDivision of Infectious Diseases, University of California, San Francisco , 513 Parnassus Avenue, Room S-380, San Francisco, CA, 94143-0654, USA
                [6 ]simpleFocal Area of Infection Biology Biozentrum, University of Basel, Klingelbergstrasse 50/70 , CH-4056 Basel, Switzerland
                Author notes
                [☆]

                This manuscript is dedicated to the memory of Professor Yves Piemont (1951–2009) from Strasbourg University (France) whose significant contribution to the field of Bartonella knowlegde expended the number of known species and its epidemiology.

                [* ]Corresponding author: bbchomel@ 123456ucdavis.edu
                Article
                10.1051/vetres/2009011 v09181
                10.1051/vetres/2009011
                2695021
                19284965
                964506bf-0f6d-4012-8a32-95b22c4692d4
                © INRA, EDP Sciences, 2009

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial License ( http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted use, distribution, and reproduction in any noncommercial medium, provided the original work is properly cited.

                History
                : 12 November 2008
                : 12 March 2009
                Page count
                Figures: 2, Tables: 0, Equations: 0, References: 141, Pages: 22
                Categories
                Review Article

                Veterinary medicine
                bartonella,ecological fitness,pathogenesis,vector,host adaptation
                Veterinary medicine
                bartonella, ecological fitness, pathogenesis, vector, host adaptation

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