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

Kraiczy, Peter

doi:10.3390/vetsci3020012

Cited by 27 publications

(30 citation statements)

References 107 publications

(187 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The two Borrelia species cycle in different classes of vertebrate hosts, rodents for B. afzelii and birds for B. garinii (33)(34)(35), and this host specificity is mediated by the vertebrate complement system (34,76). Previous work has shown that B. garinii is generally more susceptible to vertebrate complement than B. afzelii (77). We speculate that B. garinii is more susceptible to bird complement than B. afzelii is to rodent complement, which would require B. garinii to maintain a higher spirochete load in the nymphal tick than B. afzelii to achieve the same probability of infecting the vertebrate host.…”

Section: Discussionmentioning

confidence: 66%

Multistrain Infections with Lyme Borreliosis Pathogens in the Tick Vector

Durand

Herrmann

Genné

et al. 2017

Appl Environ Microbiol

View full text Add to dashboard Cite

Mixed or multiple-strain infections are common in vector-borne diseases and have important implications for the epidemiology of these pathogens. Previous studies have mainly focused on interactions between pathogen strains in the vertebrate host, but little is known about what happens in the arthropod vector. Borrelia afzelii and Borrelia garinii are two species of spirochete bacteria that cause Lyme borreliosis in Europe and that share a tick vector, Ixodes ricinus. Each of these two tick-borne pathogens consists of multiple strains that are often differentiated using the highly polymorphic ospC gene. For each Borrelia species, we studied the frequencies and abundances of the ospC strains in a wild population of I. ricinus ticks that had been sampled from the same field site over a period of 3 years. We used quantitative PCR (qPCR) and 454 sequencing to estimate the spirochete load and the strain diversity within each tick. For B. afzelii, there was a negative relationship between the two most common ospC strains, suggesting the presence of competitive interactions in the vertebrate host and possibly the tick vector. The flat relationship between total spirochete abundance and strain richness in the nymphal tick indicates that the mean abundance per strain decreases as the number of strains in the tick increases. Strains with the highest spirochete load in the nymphal tick were the most common strains in the tick population. The spirochete abundance in the nymphal tick appears to be an important life history trait that explains why some strains are more common than others in nature.IMPORTANCE Lyme borreliosis is the most common vector-borne disease in the Northern Hemisphere and is caused by spirochete bacteria that belong to the Borrelia burgdorferi sensu lato species complex. These tick-borne pathogens are transmitted among vertebrate hosts by hard ticks of the genus Ixodes. Each Borrelia species can be further subdivided into genetically distinct strains. Multiple-strain infections are common in both the vertebrate host and the tick vector and can result in competitive interactions. To date, few studies on multiple-strain vector-borne pathogens have investigated patterns of cooccurrence and abundance in the arthropod vector. We demonstrate that the abundance of a given strain in the tick vector is negatively affected by the presence of coinfecting strains. In addition, our study suggests that the spirochete abundance in the tick is an important life history trait that can explain why some strains are more common in nature than others.

show abstract

Section: Discussionmentioning

confidence: 66%

Multistrain Infections with Lyme Borreliosis Pathogens in the Tick Vector

Durand

Herrmann

Genné

et al. 2017

Appl Environ Microbiol

View full text Add to dashboard Cite

show abstract

“…This spirochete-host association has been correlated with the ability of B . burgdorferi to survive in the blood (or serum) from the corresponding hosts [ 7 , 54 – 56 ], but the mechanism that drives this association is still unclear. An attractive hypothesis is that the spirochetes exhibit host-specific immune evasion, which leads to the observed spirochete-host association.…”

Section: Discussionmentioning

confidence: 99%

“…Specific spirochete-host associations are thought to be caused by the selective ability of these spirochetes to evade innate immune responses of different hosts. One such immune response, complement, is the first-line defense mechanism in humans and other vertebrates [ 7 , 8 ].…”

Section: Introductionmentioning

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

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…Note that not every strain of Lyme borreliae species encodes CspZ (Kingry et al, ; Kraiczy, Skerka, Brade, & Zipfel, ; Rogers & Marconi, ) and allelic variations confer differential human FH/FHL‐1‐binding activity (Kraiczy et al, ; Kraiczy et al, ; Rogers et al, ). This raises the possibility that CspZ variants may determine host specificity of FH binding and determine the animals' competence to each strain (Bhide et al, ; Kraiczy, ; Kurtenbach et al, ). This could be further investigated using the quail and mouse as Lyme infection models established in this study.…”

Section: Discussionmentioning

confidence: 99%

Blood treatment of Lyme borreliae demonstrates the mechanism of CspZ ‐mediated complement evasion to promote systemic infection in vertebrate hosts

Marcinkiewicz

Dupuis

Zamba‐Campero

et al. 2019

Cellular Microbiology

Self Cite

View full text Add to dashboard Cite

Lyme disease, caused by the spirochete Borrelia burgdorferi, is the most common vector‐borne disease in the United States and Europe. The spirochetes are transmitted from mammalian and avian reservoir hosts to humans via ticks. Following tick bites, spirochetes colonize the host skin and then disseminate haematogenously to various organs, a process that requires this pathogen to evade host complement, an innate immune defence system. CspZ, a spirochete surface protein, facilitates resistance to complement‐mediated killing in vitro by binding to the complement regulator, factor H (FH). Low expression levels of CspZ in spirochetes cultivated in vitro or during initiation of infection in vivo have been a major hurdle in delineating the role of this protein in pathogenesis. Here, we show that treatment of B. burgdorferi with human blood induces CspZ production and enhances resistance to complement. By contrast, a cspZ‐deficient mutant and a strain that expressed an FH‐nonbinding CspZ variant were impaired in their ability to cause bacteraemia and colonize tissues of mice or quail; virulence of these mutants was however restored in complement C3‐deficient mice. These novel findings suggest that FH binding to CspZ facilitates B. burgdorferi complement evasion in vivo and promotes systemic infection in vertebrate hosts.

show abstract

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

Cited by 27 publications

References 107 publications

Multistrain Infections with Lyme Borreliosis Pathogens in the Tick Vector

Multistrain Infections with Lyme Borreliosis Pathogens in the Tick Vector

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

Blood treatment of Lyme borreliae demonstrates the mechanism of CspZ ‐mediated complement evasion to promote systemic infection in vertebrate hosts

Contact Info

Product

Resources

About