GAGs are long, unbranched polysaccharide molecules consisting of disaccharide repeats of modified sugars and uronic acids . Based on the degree of sulfation and the composition of the disaccharides, they are classified into heparin, heparan sulfate, chondroitin sulfate A, dermatan sulfate, chondroitin sulfate C, and keratan sulfate . GAGs are usually covalently linked to protein cores to form proteoglycans. A previous study has shown that Lyme spirochetes do not recognize JSH-23 ic50 keratan sulfate . In B. burgdorferi, several adhesins recognize GAGs and proteoglycans. We previously identified Borrelia glycosaminoglycan-NCT-501 clinical trial binding protein (Bgp), an outer membrane protein
that binds heparin and dermatan sulfate, and facilitates binding of B. burgdorferi to epithelial cells and glial cells . In addition, the B. burgdorferi surface lipoproteins TSA HDAC cost decorin-binding proteins A and B (DbpA and DbpB) recognize both decorin and dermatan sulfate [43, 51, 52]. An additional adhesin, BBK32 (fibronectin binding protein) is a surface lipoprotein that can bind both fibronectin and GAGs to promote binding of B. burgdorferi to various mammalian cells [41, 53]. P66 recognizes the integral membrane integrin receptor and was first identified as
an adhesin in the N40D10/E9 strain [54, 55] and was also shown to express in the B31 strain [56, 57]. Hence, multiple adherence mechanisms are present in B. burgdorferi emphasizing its importance in causing multisystemic Lyme disease. To evaluate the molecular mechanisms involved in B. burgdorferi
tissue colonization and multisystemic disease during mammalian infection, many different types of host cell lines can be employed to investigate Rucaparib manufacturer adherence [58–64]. For example, Vero cells, which were derived from monkey kidney epithelium , can be used as a representative of epithelial cells for studying GAGs-mediated adherence. The EA.hy926 cell line was derived from human umbilical vein endothelial cells, and it has been shown to express differentiated functions that are characteristics of human vascular endothelium [66, 67]. C6 glioma cells were derived from rat central nervous system and were previously shown to display glycosaminoglycans, heparan sulfate and chondroitin sulfates, on their surface [43, 61, 68]. The T/C-28a2 cell line was developed from human chondrocyte cells , which were shown to express fibronectin, decorin and dermatan sulfate [70, 71]. We have used these cell lines to compare the differential adherence abilities of N40D10/E9 and B31 strains. The mouse is the natural host for B. burgdorferi and the laboratory mouse model has been used to study infectivity and pathogenicity of Lyme spirochetes. Different strains of immunocompetent mice develop different degrees of pathology upon infection with B. burgdorferi. For example, C57BL/6 mice develop mild carditis and arthritis even though colonization of the tissues is relatively similar to that of disease-susceptible C3H mice [72, 73].