Live imaging reveals a biphasic mode of dissemination of Borrelia burgdorferi within ticks

Star M. Dunham-Ems, Melissa J. Caimano, Utpal Pal, Charles William Wolgemuth, Christian H. Eggers, Anamaria Balic, Justin D. Radolf

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

Lyme disease is caused by transmission of the spirochete Borrelia burgdorferi from ticks to humans. Although much is known about B. burgdorferi replication, the routes and mechanisms by which it disseminates within the tick remain unclear. To better understand this process, we imaged live, infectious B. burgdorferi expressing a stably integrated, constitutively expressed GFP reporter. Using isolated tick midguts and salivary glands, we observed B. burgdorferi progress through the feeding tick via what we believe to be a novel, biphasic mode of dissemination. In the first phase, replicating spirochetes, positioned at varying depths throughout the midgut at the onset of feeding, formed networks of nonmotile organisms that advanced toward the basolateral surface of the epithelium while adhering to differentiating, hypertrophying, and detaching epithelial cells. In the second phase of dissemination, the nonmotile spirochetes transitioned into motile organisms that penetrated the basement membrane and entered the hemocoel, then migrated to and entered the salivary glands. We designated the first phase of dissemination "adherence-mediated migration" and provided evidence that it involves the inhibition of spirochete motility by one or more diffusible factors elaborated by the feeding tick midgut. Our studies, which we believe are the first to relate the transmission dynamics of spirochetes to the complex morphological and developmental changes that the midgut and salivary glands undergo during engorgement, challenge the conventional viewpoint that dissemination of Lyme disease-causing spirochetes within ticks is exclusively motility driven.

Original languageEnglish (US)
Pages (from-to)3652-3665
Number of pages14
JournalJournal of Clinical Investigation
Volume119
Issue number12
DOIs
StatePublished - Dec 1 2009
Externally publishedYes

Fingerprint

Borrelia burgdorferi
Ticks
Spirochaetales
Salivary Glands
Lyme Disease
Basement Membrane
Epithelium
Epithelial Cells

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Dunham-Ems, S. M., Caimano, M. J., Pal, U., Wolgemuth, C. W., Eggers, C. H., Balic, A., & Radolf, J. D. (2009). Live imaging reveals a biphasic mode of dissemination of Borrelia burgdorferi within ticks. Journal of Clinical Investigation, 119(12), 3652-3665. https://doi.org/10.1172/JCI39401

Live imaging reveals a biphasic mode of dissemination of Borrelia burgdorferi within ticks. / Dunham-Ems, Star M.; Caimano, Melissa J.; Pal, Utpal; Wolgemuth, Charles William; Eggers, Christian H.; Balic, Anamaria; Radolf, Justin D.

In: Journal of Clinical Investigation, Vol. 119, No. 12, 01.12.2009, p. 3652-3665.

Research output: Contribution to journalArticle

Dunham-Ems, SM, Caimano, MJ, Pal, U, Wolgemuth, CW, Eggers, CH, Balic, A & Radolf, JD 2009, 'Live imaging reveals a biphasic mode of dissemination of Borrelia burgdorferi within ticks', Journal of Clinical Investigation, vol. 119, no. 12, pp. 3652-3665. https://doi.org/10.1172/JCI39401
Dunham-Ems, Star M. ; Caimano, Melissa J. ; Pal, Utpal ; Wolgemuth, Charles William ; Eggers, Christian H. ; Balic, Anamaria ; Radolf, Justin D. / Live imaging reveals a biphasic mode of dissemination of Borrelia burgdorferi within ticks. In: Journal of Clinical Investigation. 2009 ; Vol. 119, No. 12. pp. 3652-3665.
@article{59198b4baa7a482b87754fdd2f1f8fe9,
title = "Live imaging reveals a biphasic mode of dissemination of Borrelia burgdorferi within ticks",
abstract = "Lyme disease is caused by transmission of the spirochete Borrelia burgdorferi from ticks to humans. Although much is known about B. burgdorferi replication, the routes and mechanisms by which it disseminates within the tick remain unclear. To better understand this process, we imaged live, infectious B. burgdorferi expressing a stably integrated, constitutively expressed GFP reporter. Using isolated tick midguts and salivary glands, we observed B. burgdorferi progress through the feeding tick via what we believe to be a novel, biphasic mode of dissemination. In the first phase, replicating spirochetes, positioned at varying depths throughout the midgut at the onset of feeding, formed networks of nonmotile organisms that advanced toward the basolateral surface of the epithelium while adhering to differentiating, hypertrophying, and detaching epithelial cells. In the second phase of dissemination, the nonmotile spirochetes transitioned into motile organisms that penetrated the basement membrane and entered the hemocoel, then migrated to and entered the salivary glands. We designated the first phase of dissemination {"}adherence-mediated migration{"} and provided evidence that it involves the inhibition of spirochete motility by one or more diffusible factors elaborated by the feeding tick midgut. Our studies, which we believe are the first to relate the transmission dynamics of spirochetes to the complex morphological and developmental changes that the midgut and salivary glands undergo during engorgement, challenge the conventional viewpoint that dissemination of Lyme disease-causing spirochetes within ticks is exclusively motility driven.",
author = "Dunham-Ems, {Star M.} and Caimano, {Melissa J.} and Utpal Pal and Wolgemuth, {Charles William} and Eggers, {Christian H.} and Anamaria Balic and Radolf, {Justin D.}",
year = "2009",
month = "12",
day = "1",
doi = "10.1172/JCI39401",
language = "English (US)",
volume = "119",
pages = "3652--3665",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "12",

}

TY - JOUR

T1 - Live imaging reveals a biphasic mode of dissemination of Borrelia burgdorferi within ticks

AU - Dunham-Ems, Star M.

AU - Caimano, Melissa J.

AU - Pal, Utpal

AU - Wolgemuth, Charles William

AU - Eggers, Christian H.

AU - Balic, Anamaria

AU - Radolf, Justin D.

PY - 2009/12/1

Y1 - 2009/12/1

N2 - Lyme disease is caused by transmission of the spirochete Borrelia burgdorferi from ticks to humans. Although much is known about B. burgdorferi replication, the routes and mechanisms by which it disseminates within the tick remain unclear. To better understand this process, we imaged live, infectious B. burgdorferi expressing a stably integrated, constitutively expressed GFP reporter. Using isolated tick midguts and salivary glands, we observed B. burgdorferi progress through the feeding tick via what we believe to be a novel, biphasic mode of dissemination. In the first phase, replicating spirochetes, positioned at varying depths throughout the midgut at the onset of feeding, formed networks of nonmotile organisms that advanced toward the basolateral surface of the epithelium while adhering to differentiating, hypertrophying, and detaching epithelial cells. In the second phase of dissemination, the nonmotile spirochetes transitioned into motile organisms that penetrated the basement membrane and entered the hemocoel, then migrated to and entered the salivary glands. We designated the first phase of dissemination "adherence-mediated migration" and provided evidence that it involves the inhibition of spirochete motility by one or more diffusible factors elaborated by the feeding tick midgut. Our studies, which we believe are the first to relate the transmission dynamics of spirochetes to the complex morphological and developmental changes that the midgut and salivary glands undergo during engorgement, challenge the conventional viewpoint that dissemination of Lyme disease-causing spirochetes within ticks is exclusively motility driven.

AB - Lyme disease is caused by transmission of the spirochete Borrelia burgdorferi from ticks to humans. Although much is known about B. burgdorferi replication, the routes and mechanisms by which it disseminates within the tick remain unclear. To better understand this process, we imaged live, infectious B. burgdorferi expressing a stably integrated, constitutively expressed GFP reporter. Using isolated tick midguts and salivary glands, we observed B. burgdorferi progress through the feeding tick via what we believe to be a novel, biphasic mode of dissemination. In the first phase, replicating spirochetes, positioned at varying depths throughout the midgut at the onset of feeding, formed networks of nonmotile organisms that advanced toward the basolateral surface of the epithelium while adhering to differentiating, hypertrophying, and detaching epithelial cells. In the second phase of dissemination, the nonmotile spirochetes transitioned into motile organisms that penetrated the basement membrane and entered the hemocoel, then migrated to and entered the salivary glands. We designated the first phase of dissemination "adherence-mediated migration" and provided evidence that it involves the inhibition of spirochete motility by one or more diffusible factors elaborated by the feeding tick midgut. Our studies, which we believe are the first to relate the transmission dynamics of spirochetes to the complex morphological and developmental changes that the midgut and salivary glands undergo during engorgement, challenge the conventional viewpoint that dissemination of Lyme disease-causing spirochetes within ticks is exclusively motility driven.

UR - http://www.scopus.com/inward/record.url?scp=72849134856&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=72849134856&partnerID=8YFLogxK

U2 - 10.1172/JCI39401

DO - 10.1172/JCI39401

M3 - Article

C2 - 19920352

AN - SCOPUS:72849134856

VL - 119

SP - 3652

EP - 3665

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 12

ER -