science... it tastes like nothing else... "Borrelia Pathogenicity Pathogenicity stricto sensu and virulence of Borrelia comprise at least 2 phenomenathat are not independent of each other. Borrelia Pathogenic Potential Seems to Be Linked to Taxonomic Position. Of course, since Borrelia are strict parasites, all species are able to invade a host. However, the host spectrum as well as the clinical expression differ greatly [20] . Whenconsidering, by medical pragmatism, human sensitivity to Borrelia , the complex of 15 species is divided into 3 groups: – 4 clearly pathogenic species: B. burgdorferi s.s., B. afzelii, B. garinii and B. spielmanii – 3 rarely, if at all, pathogenic species: B. bissettii, B. lusitaniae and B. valaisiana; – 6 species (and 2 genospecies) that have never been isolated in humans (until 2009) In the Borrelia Model, Virulence Is Not Associated with Taxonomic Position. In nature, an obvious permanent selective pressure eliminates such avirulent variants that are not able to colonize their natural host. Loss of some plasmids, such as lp25 and lp28-1, is involved in a decrease in virulence [21] . Similarly the plasmid (lp25)- encoded PncA gene (nicotinamidase) has been shown to be strongly associated with virulence in Borrelia [22] . Nevertheless, virulence is an artifact only observed during in vitro experimental conditions and has not been studied further. However, theoretically it is possible that in nature the ticks may be able to diffuse avirulent Borrelia isolates by cofeeding [23] . Genes or Products of Potentially Pathogenic Genes All the genes mentioned in this section, but 2 – P66 and BgP – are plasmid encoded. Several genes have been suggested to be involved in pathogenesis. Potential adhesins, able to attach to diverse mammalian cell surface components, promote the bacterial colonization of the mammalian host. Adhesins. BgP and P66 are able to bind to platelets and integrins [24] . BbK32 (encodedon lp36) is a fibronectin adhesin [25] . DbpA and B (lp49) are decorin-binding proteins [26] . Decorin-binding proteins and BBK32 (lp36) also bind to glycosaminoglycans [27] .Other Candidate Genes for Pathogenicity. VlsE could be involved in escape from immune response by antigenic variation [28] . Complement regulator-acquiring surface factors (CRASP) are able to inhibit complement activity by combining with factor H or other similar substances of the host [29] . CRASP-1 is located on lp54, CRASP-2 on lp28-3 and CRASP 3–5 are Erp proteins encoded by the cp32 gene family [29] . CRASP from different Borrelia species, by binding with factor H of a given host, confer a corresponding serum resistance. This phenomenon could explain the host spectrum of each Borrelia species [30] . OspA (lp54), an outer surface lipoprotein, is an adhesin only expressed in vector, and is responsible for attachment to Ixodes midgut mucosa [31] . However, exceptionally,in some cases of chronic arthritis due to Borrelia , antibodies to OspA have been detected. It has been shown that an OspA motif is quite similar to human leukocyte function-associated antigen-1, which suggests it could be responsible for resistance to treatment Lyme arthritis [32] . OspA has also been involved in plasmin fixation [33] . OspC, another outer surface lipoprotein, is only expressed after the blood meal in vectors and mainly in vertebrate hosts. The ospC gene is on cp26, a very stable plasmid comprising metabolic genes [34] . In pathogenicity, ospC is a highly variable gene and plays an important role. Its expression is necessary to initiate the host colonization [35] . It has been noticed that only a limited number of ospC alleles could allow Borrelia to reach deep organs in humans after blood dissemination [36] . It has also been shown that distinct alleles of OspC bind with different affinity to plasminogen [37] . This suggests that only particular ospC alleles allow corresponding Borrelia to cross the capillary membrane of a given host species to invade its deep organs using host plasminogen. Such isolates, whose ospC allelic type is able to bind human plasminogen, are called ‘invasive’. OspC has also another indirect role. It has been discovered that salp 15, a tick saliva component, was overexpressed during the blood meal. OspC is able to bind to this and block CD4 T cell activation, leading to an increase in the Spirochaete load due to immunosuppression [38] . OspA and OspC are immunodominant outer-membrane proteins and both elicitbactericidal antibodies in hosts that are quite challenging for the strictly parasitical behavior of Borrelia . However, OspA is expressed in ticks only, and OspC local diversity represents a ‘repertoire’ that allows recontamination of a given host by a new and unrecognized ospC variant [39] . In conclusion, most of the genes that up to now have been identified as involved inpathogenicity are plasmid encoded and upregulated within the host, except the ospA gene.Moreover, autoimmunity and the general interaction of B. burgdorferi s.l. with theimmune system has also been proposed as a mechanism of pathogenicity in human Lyme borreliosis [40, 41] . Baranton, Guy and de Martin, Silvie (2009) “Borrelia burgdorferi sensu lato Diversity and Its Influence on Pathogenicity in Humans” in Lipsek and Jaulhac (eds) “Lyme Borreliosis. Biological and clinical aspects”, Karger
Posted on: Wed, 12 Jun 2013 10:16:52 +0000
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