Variable regions in the sushi domains 6–7 and 19–20 of factor H in animals and human lead to change in the affinity to factor H binding protein of Borrelia

Bhide, Mangesh; Bhide, Katarína; Pulzová, Lucia; Maďar, Marián; Mlynárčik, Patrik; Bencúrová, Elena; Hresko, Stanislav; Mucha, Rastislav

doi:10.1016/j.jprot.2012.04.013

Cited by 9 publications

(8 citation statements)

References 48 publications

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“…As wild-type B. garinii G1 did not bind FH molecules at all (Figure 1), the signals obtained are attributed to the CRASP produced in the transformed strains (see Supplementary Figure 2 for direct comparison of the FH binding pattern of wild-type and CRASP-producing strains). In this study, we observed that spirochetes producing CspA B31 and CspA Pko acquired FH and FHL-1 from human serum and FH from mouse serum, which is consistent with previous studies (59). Similarly, we found that CspA PKo was able to interact with FH from horse serum (Figure 2 and Table 2).…”

Section: Discussionsupporting

confidence: 93%

Further Insights Into the Interaction of Human and Animal Complement Regulator Factor H With Viable Lyme Disease Spirochetes

2019

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Spirochetes belonging to the Borrelia (B.) burgdorferi sensu lato (s.l.) complex differ in their ability to establish infection and to survive in diverse vertebrate hosts. Association with and adaption to various hosts most likely correlates with the spirochetes' ability to acquire complement regulator factor H (FH) to overcome the host's innate immune response. Here we assessed binding of serum FH from human and various animals including bovine, cat, chicken, dog, horse, mouse, rabbit, and rat to viable B. burgdorferi sensu stricto (s.s.), B. afzelii, B. garinii, B. spielmanii, B. valaisiana, and B. lusitaniae. Spirochetes ectopically producing CspA orthologs of B. burgdorferi s.s., B. afzelii, and B. spielmanii, CspZ, ErpC, and ErpP, respectively, were also investigated. Our comparative analysis using viable bacterial cells revealed a striking heterogeneity among Lyme disease spirochetes regarding their FH-binding patterns that almost mirrors the serum susceptibility of the respective borrelial genospecies. Moreover, native CspA from B. burgdorferi s.s., B. afzelii, and B. spielmanii as well as CspZ were identified as key ligands of FH from human, horse, and rat origin while ErpP appears to bind dog and mouse FH and to a lesser extent human FH. By contrast, ErpC did not bind FH from human as well as from animal origin. These findings indicate a strong restriction of distinct borrelial proteins toward binding of polymorphic FH of various vertebrate hosts.

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Section: Discussionsupporting

confidence: 93%

Further Insights Into the Interaction of Human and Animal Complement Regulator Factor H With Viable Lyme Disease Spirochetes

2019

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“…burgdorferi strain B31 is incapable of binding to any other vertebrate animals’ FH, when the FH has been subjected to SDS-PAGE followed by a far-western blot [ 57 ]. In contrast, FH from the serum of multiple animals including human and mouse recognizes CspA variants run on a similar blot [ 58 , 59 ]. This discrepancy may be due to structural alternations of animals’ FH on SDS-PAGE and the following far-western blot [ 8 , 22 , 23 ].…”

Section: Discussionmentioning

confidence: 99%

Polymorphic factor H-binding activity of CspA protects Lyme borreliae from the host complement in feeding ticks to facilitate tick-to-host transmission

et al. 2018

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Borrelia burgdorferi sensu lato (Bbsl), the causative agent of Lyme disease, establishes an initial infection in the host’s skin following a tick bite, and then disseminates to distant organs, leading to multisystem manifestations. Tick-to-vertebrate host transmission requires that Bbsl survives during blood feeding. Complement is an important innate host defense in blood and interstitial fluid. Bbsl produces a polymorphic surface protein, CspA, that binds to a complement regulator, Factor H (FH) to block complement activation in vitro. However, the role that CspA plays in the Bbsl enzootic cycle remains unclear. In this study, we demonstrated that different CspA variants promote spirochete binding to FH to inactivate complement and promote serum resistance in a host-specific manner. Utilizing a tick-to-mouse transmission model, we observed that a cspA-knockout B. burgdorferi is eliminated from nymphal ticks in the first 24 hours of feeding and is unable to be transmitted to naïve mice. Conversely, ectopically producing CspA derived from B. burgdorferi or B. afzelii, but not B. garinii in a cspA-knockout strain restored spirochete survival in fed nymphs and tick-to-mouse transmission. Furthermore, a CspA point mutant, CspA-L246D that was defective in FH-binding, failed to survive in fed nymphs and at the inoculation site or bloodstream in mice. We also allowed those spirochete-infected nymphs to feed on C3-/- mice that lacked functional complement. The cspA-knockout B. burgdorferi or this mutant strain complemented with cspA variants or cspA-L246D was found at similar levels as wild type B. burgdorferi in the fed nymphs and mouse tissues. These novel findings suggest that the FH-binding activity of CspA protects spirochetes from complement-mediated killing in fed nymphal ticks, which ultimately allows Bbsl transmission to mammalian hosts.

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“…A series of studies clearly demonstrated that purified, as well as surface-exposed, CspA of B. burgdorferi s.s. and B. afzelii bind to human Factor H [ 75 , 82 , 87 , 88 , 89 ] while contradictory data have been reported for the binding of mouse Factor H to CspA, perhaps owing to the different approaches used to assess the protein-protein interactions [ 75 , 89 ]. Furthermore, binding of Factor H from other competent hosts (dog, rat, rabbit, cat, sheep, horse, cow) has not been observed, leading to the conclusion that CspA might not play a prominent role in immune evasion in these potential reservoirs [ 75 ].…”

Section: The Role Of Factor H-binding Complement-acquiring Surfacementioning

confidence: 99%

“… Symbols in parenthesis indicate controversial results of Factor H binding to the respective CRASP protein. Further studies are required to unambiguously determine whether the respective proteins interact with factor H; a binding of human and animal factor H to purified proteins was assessed by different Western blotting approaches [ 70 , 72 , 75 , 77 , 78 , 88 , 89 , 95 ]; ND, no data available; Bb, B. burgdorferi s.s.; Ba, B. afzelii ; Csp, complement regulator-acquiring surface protein; Erp, OspE/F-related protein; synonyms of protein names are indicated in brackets. …”

Section: Figurementioning

confidence: 99%

Travelling between Two Worlds: Complement as a Gatekeeper for an Expanded Host Range of Lyme Disease Spirochetes

Kraiczy

2016

Veterinary Sciences

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Evading innate immunity is a prerequisite for pathogenic microorganisms in order to survive in their respective hosts. Concerning Lyme disease spirochetes belonging to the Borrelia (B.) burgdorferi sensu lato group, a broad range of diverse vertebrates serve as reservoir or even as incidental hosts, including humans. The capability to infect multiple hosts implies that spirochetes have developed sophisticated means to counter the destructive effects of complement of humans and various animals. While the means by which spirochetes overcome the hosts immune defense are far from being completely understood, there is a growing body of evidence suggesting that binding of the key regulator of the alternative pathway, Factor H, plays a pivotal role for immune evasion and that Factor H is an important determinant of host specificity. This review covers (i) the contribution of complement in host-specificity and transmissibility of Lyme disease spirochetes; (ii) the involvement of borrelial-derived determinants to host specificity; (iii) the interplay of human and animal Factor H with complement-acquiring surface proteins of diverse borrelial species; and (iv) the potential role of additional animal complement proteins in the immune evasion of spirochetes.

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Variable regions in the sushi domains 6–7 and 19–20 of factor H in animals and human lead to change in the affinity to factor H binding protein of Borrelia

Cited by 9 publications

References 48 publications

Further Insights Into the Interaction of Human and Animal Complement Regulator Factor H With Viable Lyme Disease Spirochetes

Further Insights Into the Interaction of Human and Animal Complement Regulator Factor H With Viable Lyme Disease Spirochetes

Polymorphic factor H-binding activity of CspA protects Lyme borreliae from the host complement in feeding ticks to facilitate tick-to-host transmission

Travelling between Two Worlds: Complement as a Gatekeeper for an Expanded Host Range of Lyme Disease Spirochetes

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