The lipoprotein La7 contributes to Borrelia burgdorferi persistence in ticks and their transmission to naïve hosts

Yang, Xiuli; Hegde, Shylaja; Shroder, Deborah Y.; Smith, Alexis A.; Promnares, Kamoltip; Neelakanta, Girish; Anderson, John F.; Fikrig, Erol; Pal, Utpal

doi:10.1016/j.micinf.2013.06.001

Cited by 16 publications

(10 citation statements)

References 45 publications

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“…With regard to PPIs involved in vector–pathogen–mammalian host interphases, the Borrelia burgdorferi field (causative agent of Lyme disease) is setting the trend with interactions described for BB0323 and BB0323 as well as OspA and CD40 . Additional targets of interest include the tetratricopeptide repeat domain of BB0238 and La7 . Currently, interactomes of tick tissues of interest for vaccination as well as the tick–pathogen and tick–host interphases remain unexplored.…”

Section: Insight From Tick Protein Evolution: Targeting Of Binding Spmentioning

confidence: 99%

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Strategies for new and improved vaccines against ticks and tick‐borne diseases

Fuente

Kopáček

Lew-Tabor

et al. 2016

Parasite Immunology

115

105

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SUMMARYTicks infest a variety of animal species and transmit pathogens causing disease in both humans and animals worldwide. Tick-host-pathogen interactions have evolved through dynamic processes that accommodated the genetic traits of the hosts, pathogens transmitted and the vector tick species that mediate their development and survival. New approaches for tick control are dependent on defining molecular interactions between hosts, ticks and pathogens to allow for discovery of key molecules that could be tested in vaccines or new generation therapeutics for intervention of tick-pathogen cycles. Currently, tick vaccines constitute an effective and environmentally sound approach for the control of ticks and the transmission of the associated tick-borne diseases. New candidate protective antigens will most likely be identified by focusing on proteins with relevant biological function in the feeding, reproduction, development, immune response, subversion of host immunity of the tick vector and/ or molecules vital for pathogen infection and transmission. This review addresses different approaches and strategies used for the discovery of protective antigens, including focusing on relevant tick biological functions and proteins, reverse genetics, vaccinomics and tick protein evolution and interactomics. New and improved tick vaccines will most likely contain multiple antigens to control tick infestations and pathogen infection and transmission.

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Section: Insight From Tick Protein Evolution: Targeting Of Binding Spmentioning

confidence: 99%

“…BB0323 (158,159) as well as OspA and CD40 (160). Additional targets of interest include the tetratricopeptide repeat domain of BB0238 (161) and La7 (162). Currently, interactomes of tick tissues of interest for vaccination as well as the tick-pathogen and tick-host interphases remain unexplored.…”

Section: Protein-protein Interactions and Metabolic Pathwaysmentioning

confidence: 99%

Strategies for new and improved vaccines against ticks and tick‐borne diseases

Fuente

Kopáček

Lew-Tabor

et al. 2016

Parasite Immunology

115

105

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“…Immunoblotting assays were performed by standard procedures as detailed elsewhere (28). Briefly, wholecell lysates of B. burgdorferi grown in BSK-II medium at 34°C and 37°C were resolved by SDS-PAGE, transferred to a nitrocellulose membrane, and probed with anti-BB0323 (1:3,000), anti-BB0238 (1:3,000), anti-BB0365 (1:1,000), and anti-BbHtrA (1:3,000) antibodies (28,39). Immunoblot assays were developed by the addition of horseradish peroxidase (HRP)-conjugated secondary antibodies (1:5,000 to 10,000) and enhanced chemiluminescence as previously described (28).…”

Section: Methodsmentioning

confidence: 99%

HtrA, a Temperature- and Stationary Phase-Activated Protease Involved in Maturation of a Key Microbial Virulence Determinant, Facilitates Borrelia burgdorferi Infection in Mammalian Hosts

Sharma

Thakur

et al. 2016

Infect Immun

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d High-temperature requirement protease A (HtrA) represents a family of serine proteases that play important roles in microbial biology. Unlike the genomes of most organisms, that of Borrelia burgdorferi notably encodes a single HtrA gene product, termed BbHtrA. Previous studies identified a few substrates of BbHtrA; however, their physiological relevance could not be ascertained, as targeted deletion of the gene has not been successful. Here we show that BbhtrA transcripts are induced during spirochete growth either in the stationary phase or at elevated temperature. Successful generation of a BbhtrA deletion mutant and restoration by genetic complementation suggest a nonessential role for this protease in microbial viability; however, its remarkable growth, morphological, and structural defects during cultivation at 37°C confirm a high-temperature requirement for protease activation and function. The BbhtrA-deficient spirochetes were unable to establish infection of mice, as evidenced by assessment of culture, PCR, and serology. We show that transcript abundance as well as proteolytic processing of a borrelial protein required for cell fission and infectivity, BB0323, is impaired in BbhtrA mutants grown at 37°C, which likely contributed to their inability to survive in a mammalian host. Together, these results demonstrate the physiological relevance of a unique temperature-regulated borrelial protease, BbHtrA, which further enlightens our knowledge of intriguing aspects of spirochete biology and infectivity. L yme disease is a common vector-borne infectious disease in the Northern Hemisphere, posing a serious health threat to humans and animals (1-3). Newly revised estimates from the Centers for Disease Control and Prevention suggest that there are likely to be over 300,000 new cases per year in the United States alone, and a vaccine to prevent human infection is currently unavailable. The disease can be transmitted via the bite of the infected arthropod vector, the Ixodes scapularis tick, harboring the spirochete pathogen Borrelia burgdorferi, often resulting in serious illness in susceptible hosts (2, 3). While most Lyme disease cases can be treated with an antibiotic, a minority of patients will have persistent or relapsing nonobjective symptoms that vary in intensity, are nonresponsive to further antibiotic therapy, and are collectively termed chronic Lyme disease or posttreatment Lyme disease syndrome, the underlying mechanism and pathogenesis of which remain highly controversial (4). Detection of early Lyme disease, when antibiotic treatment is most effective, also remains challenging, as the infection reflects many nonspecific symptoms that are shared by many other febrile or influenza-like diseases (5, 6). Thus, the development of efficient diagnostics, vaccines, or new effective drugs is a high-priority goal that requires a thorough understanding of the unusual biology and infection process of this pathogen.The pathogen of Lyme disease exhibits evolutionary divergence from other bacteria, even related...

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“…bb0405 encodes a surface-exposed transmembrane protein and mutants were unable to transmit from ticks to mice (Kung et al, 2016). The subsurface membrane protein LA7 (p22), encoded by bb0365 , supports survival in the tick (Pal et al, 2008); LA7-deficient B. burgdorferi were severely impaired in their ability to persist in feeding and quiescent ticks during transmission and intermolt (Yang et al, 2013a). Dps/NapA/BicA (BB0690) is an ortholog of bacterioferritin that is uniquely fused to a copper-binding metallothionein-like domain (Wang et al, 2012).…”

Section: Gene Products Required In the Tickmentioning

confidence: 99%

Interaction of the Lyme disease spirochete with its tick vector

Caimano

Drecktrah

Kung

et al. 2016

Cellular Microbiology

121

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Summary Borrelia burgdorferi , the causative agent of Lyme disease (along with closely related genospecies), is in the deeply branching spirochete phylum. The bacterium is maintained in nature in an enzootic cycle that involves transmission from a tick vector to a vertebrate host and acquisition from a vertebrate host to a tick vector. During its arthropod sojourn, B. burgdorferi faces a variety of stresses, including nutrient deprivation. Here, we review some of the spirochetal factors that promote persistence, maintenance and dissemination of B. burgdorferi in the tick, and then focus on the utilization of available carbohydrates as well as the exquisite regulatory systems invoked to adapt to the austere environment between blood meals and to signal species transitions as the bacteria traverse their enzootic cycle. The spirochetes shift their source of carbon and energy from glucose in the vertebrate to glycerol in the tick. Regulation of survival under limiting nutrients requires the classic stringent response in which RelBbu controls the levels of the alarmones guanosine tetraphosphate and guanosine pentaphosphate (collectively termed (p)ppGpp), while regulation at the tick–vertebrate interface as well as regulation of protective responses to the blood meal require the two-component system Hk1/Rrp1 to activate production of the second messenger cyclic-dimeric-GMP (c-di-GMP).

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The lipoprotein La7 contributes to Borrelia burgdorferi persistence in ticks and their transmission to naïve hosts

Cited by 16 publications

References 45 publications

Strategies for new and improved vaccines against ticks and tick‐borne diseases

Strategies for new and improved vaccines against ticks and tick‐borne diseases

HtrA, a Temperature- and Stationary Phase-Activated Protease Involved in Maturation of a Key Microbial Virulence Determinant, Facilitates Borrelia burgdorferi Infection in Mammalian Hosts

Interaction of the Lyme disease spirochete with its tick vector

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