Limits...
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.

Show MeSH

Related in: MedlinePlus

bbe31 expression profile throughout representative stages of the natural spirochete life cycle.bbe31 is preferentially expressed in fed tick. It is induced from the 2nd day, expressed in all the tested tissues including gut, hemolymph and salivary glands, and showed the highest expression level in the fed gut. Both mean and SD were calculated from 2 independent experiments, with 3 mRNA samples each experiment. In vitro, B.burgdorferi N40 grown in BSK medium with a concentration of 1×107/ml; Larva, I.scapularis larva fed on N40-infected mouse till engorged; day4, larva 4-day after feeding; day 21; larva 21-day after feeding; day1 Gut, day2 Gut and day3 Gut, guts of N40-nymphs feeding on C3H mice for 24, 48 and 72 hours; SG, salivary glands; HL, hemolymph; Injection, mouse inoculated with 1*106 B.burgdorferi N40; day1, day2 and day3, mouse localized skin 24, 48 or 72 hours after B.burgdorferi N40 infection through needle inoculation; skin, heart, bladder and joint, mouse tissues collected 21 days after N40-infected nymphs feeding on C3H mice.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3111543&req=5

ppat-1002079-g001: bbe31 expression profile throughout representative stages of the natural spirochete life cycle.bbe31 is preferentially expressed in fed tick. It is induced from the 2nd day, expressed in all the tested tissues including gut, hemolymph and salivary glands, and showed the highest expression level in the fed gut. Both mean and SD were calculated from 2 independent experiments, with 3 mRNA samples each experiment. In vitro, B.burgdorferi N40 grown in BSK medium with a concentration of 1×107/ml; Larva, I.scapularis larva fed on N40-infected mouse till engorged; day4, larva 4-day after feeding; day 21; larva 21-day after feeding; day1 Gut, day2 Gut and day3 Gut, guts of N40-nymphs feeding on C3H mice for 24, 48 and 72 hours; SG, salivary glands; HL, hemolymph; Injection, mouse inoculated with 1*106 B.burgdorferi N40; day1, day2 and day3, mouse localized skin 24, 48 or 72 hours after B.burgdorferi N40 infection through needle inoculation; skin, heart, bladder and joint, mouse tissues collected 21 days after N40-infected nymphs feeding on C3H mice.

Mentions: Detailed expression profiling is useful for investigations of the potential location for gene function. In this study, we measured bbe31 expression throughout representative stages of the natural spirochete life (Figure 1), including the spirochete acquisition by larva when feeding on B.burgdoferi infected-C3H mice (Acquisition), persistence through the molting period (Persistence), transmission from infected nymph to clean C3H mice during nymph feeding (Transmission), survival from the host innate immune system (Injection) and successful infection of several murine host tissues (Tick feeding). We found that bbe31 is not expressed during larva acquisition and the molting period. It is also not expressed in the murine host. The gene is expressed at very low level in vitro and in unfed nymph. Compare to the expression in unfed nymph, bbe31 is greatly induced during tick feeding. Although expression was induced in all the three tested tissues including tick gut, hemolymph and salivary glands from the 2nd day of feeding, the highest expression level was seen in tick gut. This suggests that BBE31 may play a role during B.burgdoferi transmission from tick to the murine host.


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)

bbe31 expression profile throughout representative stages of the natural spirochete life cycle.bbe31 is preferentially expressed in fed tick. It is induced from the 2nd day, expressed in all the tested tissues including gut, hemolymph and salivary glands, and showed the highest expression level in the fed gut. Both mean and SD were calculated from 2 independent experiments, with 3 mRNA samples each experiment. In vitro, B.burgdorferi N40 grown in BSK medium with a concentration of 1×107/ml; Larva, I.scapularis larva fed on N40-infected mouse till engorged; day4, larva 4-day after feeding; day 21; larva 21-day after feeding; day1 Gut, day2 Gut and day3 Gut, guts of N40-nymphs feeding on C3H mice for 24, 48 and 72 hours; SG, salivary glands; HL, hemolymph; Injection, mouse inoculated with 1*106 B.burgdorferi N40; day1, day2 and day3, mouse localized skin 24, 48 or 72 hours after B.burgdorferi N40 infection through needle inoculation; skin, heart, bladder and joint, mouse tissues collected 21 days after N40-infected nymphs feeding on C3H mice.
© Copyright Policy
Related In: Results  -  Collection

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

ppat-1002079-g001: bbe31 expression profile throughout representative stages of the natural spirochete life cycle.bbe31 is preferentially expressed in fed tick. It is induced from the 2nd day, expressed in all the tested tissues including gut, hemolymph and salivary glands, and showed the highest expression level in the fed gut. Both mean and SD were calculated from 2 independent experiments, with 3 mRNA samples each experiment. In vitro, B.burgdorferi N40 grown in BSK medium with a concentration of 1×107/ml; Larva, I.scapularis larva fed on N40-infected mouse till engorged; day4, larva 4-day after feeding; day 21; larva 21-day after feeding; day1 Gut, day2 Gut and day3 Gut, guts of N40-nymphs feeding on C3H mice for 24, 48 and 72 hours; SG, salivary glands; HL, hemolymph; Injection, mouse inoculated with 1*106 B.burgdorferi N40; day1, day2 and day3, mouse localized skin 24, 48 or 72 hours after B.burgdorferi N40 infection through needle inoculation; skin, heart, bladder and joint, mouse tissues collected 21 days after N40-infected nymphs feeding on C3H mice.
Mentions: Detailed expression profiling is useful for investigations of the potential location for gene function. In this study, we measured bbe31 expression throughout representative stages of the natural spirochete life (Figure 1), including the spirochete acquisition by larva when feeding on B.burgdoferi infected-C3H mice (Acquisition), persistence through the molting period (Persistence), transmission from infected nymph to clean C3H mice during nymph feeding (Transmission), survival from the host innate immune system (Injection) and successful infection of several murine host tissues (Tick feeding). We found that bbe31 is not expressed during larva acquisition and the molting period. It is also not expressed in the murine host. The gene is expressed at very low level in vitro and in unfed nymph. Compare to the expression in unfed nymph, bbe31 is greatly induced during tick feeding. Although expression was induced in all the three tested tissues including tick gut, hemolymph and salivary glands from the 2nd day of feeding, the highest expression level was seen in tick gut. This suggests that BBE31 may play a role during B.burgdoferi transmission from tick to the murine host.

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