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Molecular interactions that enable movement of the Lyme disease agent from the tick gut into the hemolymph.

Zhang L, Zhang Y, Adusumilli S, Liu L, Narasimhan S, Dai J, Zhao YO, Fikrig E - PLoS Pathog. (2011)

Bottom Line: The decreased hemolymph infection results in lower salivary glands infection, and consequently attenuates mouse infection by tick-transmitted B. burgdorferi.Silencing tre31 also decreased the B. burgdorferi burden in the tick hemolymph.Delineating the specific spirochete and arthropod ligands required for B. burgdorferi movement in the tick may lead to new strategies to interrupt the life cycle of the Lyme disease agent.

View Article: PubMed Central - PubMed

Affiliation: Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America.

ABSTRACT
Borrelia burgdorferi, the causative agent of Lyme disease, is transmitted to humans by bite of Ixodes scapularis ticks. The mechanisms by which the bacterium is transmitted from vector to host are poorly understood. In this study, we show that the F(ab)(2) fragments of BBE31, a B.burgdorferi outer-surface lipoprotein, interfere with the migration of the spirochete from tick gut into the hemolymph during tick feeding. The decreased hemolymph infection results in lower salivary glands infection, and consequently attenuates mouse infection by tick-transmitted B. burgdorferi. Using a yeast surface display approach, a tick gut protein named TRE31 was identified to interact with BBE31. Silencing tre31 also decreased the B. burgdorferi burden in the tick hemolymph. Delineating the specific spirochete and arthropod ligands required for B. burgdorferi movement in the tick may lead to new strategies to interrupt the life cycle of the Lyme disease agent.

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Influence of BBE31 antibodies on B.burgdorferi infectivity in mice.(A) BBE31 antibodies protect mouse from infection by tick-transmitted B. burgdorferi. Six of N40-infected nymphs were placed on 1 mouse, which has been injected with normal rabbit serum (NRS), BBE31 antiserum (E31) or BBI16 antiserum (I16), allowing to feed till exhausted. Twenty-one days later, the B. burgdorferi burden in mouse skin, bladder, heart and joints tissues were measured by q-PCR. Each dot represents 1 mouse. *: p<0.05, **: p<0.01. (B) BBE31 antibodies can't protect mice from infection by needle-inoculated B. burgdorferi. Mice were injected with rabbit normal serum (NRS) or BBE31 antiserum (E31). Twenty-four hours later, 102 of cultured B.burgdorferi N40 were intraperitoneally inoculated into the mice. B.burgdorferi burden in murine tissues were measured 21 days after Borrelia inoculation. Each dot represents 1 mouse. (C) Mice protection by BBE31 antiserum determined by in vitro culture of skin, bladder, heart and joints. Mice tissues used for culture were the same as those described above (4A and 4B). 102 Bb inoculation and 103 Bb inoculation: 102 or 103 of B.burgdorferi N40 in BSK medium were needle-inoculated into each C3H mouse. NA: not assayed.
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ppat-1002079-g004: Influence of BBE31 antibodies on B.burgdorferi infectivity in mice.(A) BBE31 antibodies protect mouse from infection by tick-transmitted B. burgdorferi. Six of N40-infected nymphs were placed on 1 mouse, which has been injected with normal rabbit serum (NRS), BBE31 antiserum (E31) or BBI16 antiserum (I16), allowing to feed till exhausted. Twenty-one days later, the B. burgdorferi burden in mouse skin, bladder, heart and joints tissues were measured by q-PCR. Each dot represents 1 mouse. *: p<0.05, **: p<0.01. (B) BBE31 antibodies can't protect mice from infection by needle-inoculated B. burgdorferi. Mice were injected with rabbit normal serum (NRS) or BBE31 antiserum (E31). Twenty-four hours later, 102 of cultured B.burgdorferi N40 were intraperitoneally inoculated into the mice. B.burgdorferi burden in murine tissues were measured 21 days after Borrelia inoculation. Each dot represents 1 mouse. (C) Mice protection by BBE31 antiserum determined by in vitro culture of skin, bladder, heart and joints. Mice tissues used for culture were the same as those described above (4A and 4B). 102 Bb inoculation and 103 Bb inoculation: 102 or 103 of B.burgdorferi N40 in BSK medium were needle-inoculated into each C3H mouse. NA: not assayed.

Mentions: We then investigated whether the lower salivary glands infection consequently resulted in decreased mouse infection. N40-infected nymphs were placed on C3H mice injected with normal rabbit serum, BBE31 or BBI16 antiserum 24 hours prior to tick feeding. Ticks were allowed to feed to replete. Twenty-one days after tick feeding, mice were sacrificed and tissues including skin, heart, bladder and joints were cultured for spirochete growth. All mice treated with normal rabbit serum or BBI16 antiserum were infected. In contrast, only 2 of 6 mice treated with BBE31 antiserum were infected (Figure 4C). Q-PCR results showed that the infection level of mice treated by BBE31 antiserum was significantly lower than in animals treated by NRS or BBI16 antiserum (Figure 4A). This result suggests that BBE31 antiserum can partially protect mice from infection by tick-transmitted B.burgdorferi.


Molecular interactions that enable movement of the Lyme disease agent from the tick gut into the hemolymph.

Zhang L, Zhang Y, Adusumilli S, Liu L, Narasimhan S, Dai J, Zhao YO, Fikrig E - PLoS Pathog. (2011)

Influence of BBE31 antibodies on B.burgdorferi infectivity in mice.(A) BBE31 antibodies protect mouse from infection by tick-transmitted B. burgdorferi. Six of N40-infected nymphs were placed on 1 mouse, which has been injected with normal rabbit serum (NRS), BBE31 antiserum (E31) or BBI16 antiserum (I16), allowing to feed till exhausted. Twenty-one days later, the B. burgdorferi burden in mouse skin, bladder, heart and joints tissues were measured by q-PCR. Each dot represents 1 mouse. *: p<0.05, **: p<0.01. (B) BBE31 antibodies can't protect mice from infection by needle-inoculated B. burgdorferi. Mice were injected with rabbit normal serum (NRS) or BBE31 antiserum (E31). Twenty-four hours later, 102 of cultured B.burgdorferi N40 were intraperitoneally inoculated into the mice. B.burgdorferi burden in murine tissues were measured 21 days after Borrelia inoculation. Each dot represents 1 mouse. (C) Mice protection by BBE31 antiserum determined by in vitro culture of skin, bladder, heart and joints. Mice tissues used for culture were the same as those described above (4A and 4B). 102 Bb inoculation and 103 Bb inoculation: 102 or 103 of B.burgdorferi N40 in BSK medium were needle-inoculated into each C3H mouse. NA: not assayed.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3111543&req=5

ppat-1002079-g004: Influence of BBE31 antibodies on B.burgdorferi infectivity in mice.(A) BBE31 antibodies protect mouse from infection by tick-transmitted B. burgdorferi. Six of N40-infected nymphs were placed on 1 mouse, which has been injected with normal rabbit serum (NRS), BBE31 antiserum (E31) or BBI16 antiserum (I16), allowing to feed till exhausted. Twenty-one days later, the B. burgdorferi burden in mouse skin, bladder, heart and joints tissues were measured by q-PCR. Each dot represents 1 mouse. *: p<0.05, **: p<0.01. (B) BBE31 antibodies can't protect mice from infection by needle-inoculated B. burgdorferi. Mice were injected with rabbit normal serum (NRS) or BBE31 antiserum (E31). Twenty-four hours later, 102 of cultured B.burgdorferi N40 were intraperitoneally inoculated into the mice. B.burgdorferi burden in murine tissues were measured 21 days after Borrelia inoculation. Each dot represents 1 mouse. (C) Mice protection by BBE31 antiserum determined by in vitro culture of skin, bladder, heart and joints. Mice tissues used for culture were the same as those described above (4A and 4B). 102 Bb inoculation and 103 Bb inoculation: 102 or 103 of B.burgdorferi N40 in BSK medium were needle-inoculated into each C3H mouse. NA: not assayed.
Mentions: We then investigated whether the lower salivary glands infection consequently resulted in decreased mouse infection. N40-infected nymphs were placed on C3H mice injected with normal rabbit serum, BBE31 or BBI16 antiserum 24 hours prior to tick feeding. Ticks were allowed to feed to replete. Twenty-one days after tick feeding, mice were sacrificed and tissues including skin, heart, bladder and joints were cultured for spirochete growth. All mice treated with normal rabbit serum or BBI16 antiserum were infected. In contrast, only 2 of 6 mice treated with BBE31 antiserum were infected (Figure 4C). Q-PCR results showed that the infection level of mice treated by BBE31 antiserum was significantly lower than in animals treated by NRS or BBI16 antiserum (Figure 4A). This result suggests that BBE31 antiserum can partially protect mice from infection by tick-transmitted B.burgdorferi.

Bottom Line: The decreased hemolymph infection results in lower salivary glands infection, and consequently attenuates mouse infection by tick-transmitted B. burgdorferi.Silencing tre31 also decreased the B. burgdorferi burden in the tick hemolymph.Delineating the specific spirochete and arthropod ligands required for B. burgdorferi movement in the tick may lead to new strategies to interrupt the life cycle of the Lyme disease agent.

View Article: PubMed Central - PubMed

Affiliation: Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America.

ABSTRACT
Borrelia burgdorferi, the causative agent of Lyme disease, is transmitted to humans by bite of Ixodes scapularis ticks. The mechanisms by which the bacterium is transmitted from vector to host are poorly understood. In this study, we show that the F(ab)(2) fragments of BBE31, a B.burgdorferi outer-surface lipoprotein, interfere with the migration of the spirochete from tick gut into the hemolymph during tick feeding. The decreased hemolymph infection results in lower salivary glands infection, and consequently attenuates mouse infection by tick-transmitted B. burgdorferi. Using a yeast surface display approach, a tick gut protein named TRE31 was identified to interact with BBE31. Silencing tre31 also decreased the B. burgdorferi burden in the tick hemolymph. Delineating the specific spirochete and arthropod ligands required for B. burgdorferi movement in the tick may lead to new strategies to interrupt the life cycle of the Lyme disease agent.

Show MeSH
Related in: MedlinePlus