This proposal will characterize the influence of tick gut microbiota on the ability of Borrelia burgdorferi, the Lyme disease agent, to be transmitted from ticks to the vertebrate host. Our recent work (Narasimhan et al, Cell Host Microbe 15:58-71, 2014) demonstrated that tick gut microbiota modulate B. burgdorferi colonization of Ixodes scapularis. Our preliminary data suggest that normal gut microbiota facilitate efficient B. burgdorferi transmission to the mammalian host. This is a critical event in the context of human Lyme disease and understanding how tick gut microbiota influence Borrelia transmission to the mammalian host will reveal new ways to prevent Lyme disease transmission.
In Aim 1 we will characterize and determine tick gut bacterial profiles that are associated with decreased B. burgdorferi transmission to the vertebrate host. Further, we will also begin to assess the microbial compositions of nymphal ticks obtained from endemic regions in Connecticut to co-relate our observations on lab-reared ticks. Application of this knowledge to field studies in future efforts might provide new predictors/biomarkers of transmission risk in specific geographic areas.
In Aim 2 we will perform a transcriptome analysis of the tick gut to describe the molecular pathways of the tick that are influenced by gut microbiota during B. burgdorferi transmission. With a focus on up to 10 genes that are significantly altered by gut microbiota we will determine their functional consequence on B. burgdorferi transmission. Potential vaccine targets to impair Borrelia transmission may be identified from this functional analysis. Finally, we will determine if dysbiosis might modulate the expression profiles of Borrelial virulence genes, and additionally influence spirochete transmission to the host. We will focus on the lipoprotein encoding virulence genes of B. burgdorferi and unravel a new understanding of how B. burgdorferi senses the tick gut environment to regulate the expression of virulence genes. This research effort will move the field beyond a descriptive understanding of tick gut microbiota, and unfold a mechanistic understanding of the influence of tick gut bacteria on tick-pathogen interactions in particular, and on vector-pathogen interactions in general. Tick gut microbiota provides a new vantage point to understand the biology of B. burgdorferi transmission to mice and to develop new paradigms to explore the factors that contribute to the spread of Lyme disease.

Public Health Relevance

The tick, Ixodes scapularis, is a major vector of the Lyme disease spirochete Borrelia burgdorferi. The proposal will examine the role of tick gut microbiota, an emerging player in modulating tick-spirochete interactions, in B. burgdorferi transmission to the mammalian host.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI126033-01A1
Application #
9307125
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Ilias, Maliha R
Project Start
2017-08-10
Project End
2021-07-31
Budget Start
2017-08-10
Budget End
2018-07-31
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Yale University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Shaw, Dana K; Tate, Ann T; Schneider, David S et al. (2018) Vector Immunity and Evolutionary Ecology: The Harmonious Dissonance. Trends Immunol 39:862-873
Abraham, Nabil M; Liu, Lei; Jutras, Brandon Lyon et al. (2017) Pathogen-mediated manipulation of arthropod microbiota to promote infection. Proc Natl Acad Sci U S A 114:E781-E790
Ansari, Juliana M; Abraham, Nabil M; Massaro, Jenna et al. (2017) Anti-Biofilm Activity of a Self-Aggregating Peptide against Streptococcus mutans. Front Microbiol 8:488
Abraham, Nabil M; Liu, Lei; Jutras, Brandon L et al. (2017) A Tick Antivirulence Protein Potentiates Antibiotics against Staphylococcus aureus. Antimicrob Agents Chemother 61: