Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P36980 (CFHR2)
 30 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Borrelia burgdorferi, the etiological agent of Lyme disease, exploits an array of strategies to establish infection and to overcome host innate and adaptive immune responses. One key borrelial immune escape mechanism involves the inactivation of host complement attack through acquisition of human immune regulators factor H (CFH), factor H-like protein 1 (FHL1), factor H-related protein 1 (CFHR1), CFHR2, and/or CFHR5. Binding of these host proteins is primarily mediated by bacterial surface-exposed proteins that have been collectively referred to as complement regulator-acquiring surface proteins, or CRASPs. Different strains of B. burgdorferi produce as many as 5 different CRASP molecules that comprise 3 distinct, genetically unrelated groups. Depending on bacterial genetic composition, different combinations of these proteins can be found on the borrelial outer surface. The 3 groups differ in their gene location, gene regulatory mechanisms, expression patterns during the tick-mammal infection cycle, protein sequence and structure as well as binding affinity for complement regulators and other serum proteins. These attributes influence the proteins' abilities to contribute to complement resistance of this emerging human pathogen. In this review, we focus on the current knowledge on structure, function, and gene regulation of these B. burgdorferi infection-associated proteins.
 ...
PMID:Complement regulator-acquiring surface proteins of Borrelia burgdorferi: Structure, function and regulation of gene expression. 2321 63

Overcoming the first line of the innate immune system is a general hallmark of pathogenic microbes to avoid recognition and to enter the human host. In particular, spirochetes belonging to the Borrelia burgdorferi sensu lato complex have developed various means to counter the immune response and to successfully survive in diverse host environments for a prolonged period of time. In regard to complement resistance, Borrelia utilize a plethora of immune evasion strategies involves capturing of host-derived complement regulators, terminating complement activation as well as shedding of cell-destroying complement complexes to manipulate and to expeditiously inhibit human complement. Owing to their mode of action, the interacting surface-exposed proteins identified among B. burgdorferi sensu stricto (s.s.), Borrelia afzelii, Borrelia spielmanii, and Borrelia bavariensis can be classified into at least two major categories, namely, molecules that directly interfere with distinct complement components including BBK32, CspA, BGA66, BGA71, and a CD59-like protein or molecules, which indirectly counteract complement activation by binding various complement regulators such as Factor H, Factor H-like protein 1 (FHL-1), Factor H-related proteins FHR-1, FHR-2, or C4Bp. The latter group of genetically and structurally unrelated proteins has been collectively referred to as "complement regulator-acquiring surface proteins" and consists of CspA, CspZ, ErpA, ErpC, ErpP, and the as yet unidentified protein p43. This review focuses on the current knowledge of immune evasion mechanisms exhibited by Lyme disease spirochetes and highlights the role of complement-interfering, infection-associated molecules playing an important part in these processes. Deciphering the immune evasion strategies may provide novel avenues for improved diagnostic approaches and therapeutic interventions.
 ...
PMID:Hide and Seek: How Lyme Disease Spirochetes Overcome Complement Attack. 2772 20