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Genome-wide screen identifies novel genes required for Borrelia burgdorferi survival in its Ixodes tick vector.
- Source :
-
PLoS pathogens [PLoS Pathog] 2019 May 14; Vol. 15 (5), pp. e1007644. Date of Electronic Publication: 2019 May 14 (Print Publication: 2019). - Publication Year :
- 2019
-
Abstract
- Borrelia burgdorferi, the causative agent of Lyme disease in humans, is maintained in a complex biphasic life cycle, which alternates between tick and vertebrate hosts. To successfully survive and complete its enzootic cycle, B. burgdorferi adapts to diverse hosts by regulating genes required for survival in specific environments. Here we describe the first ever use of transposon insertion sequencing (Tn-seq) to identify genes required for B. burgdorferi survival in its tick host. We found that insertions into 46 genes resulted in a complete loss of recovery of mutants from larval Ixodes ticks. Insertions in an additional 56 genes resulted in a >90% decrease in fitness. The screen identified both previously known and new genes important for larval tick survival. Almost half of the genes required for survival in the tick encode proteins of unknown function, while a significant portion (over 20%) encode membrane-associated proteins or lipoproteins. We validated the results of the screen for five Tn mutants by performing individual competition assays using mutant and complemented strains. To better understand the role of one of these genes in tick survival, we conducted mechanistic studies of bb0017, a gene previously shown to be required for resistance against oxidative stress. In this study we show that BB0017 affects the regulation of key borrelial virulence determinants. The application of Tn-seq to in vivo screening of B. burgdorferi in its natural vector is a powerful tool that can be used to address many different aspects of the host pathogen interaction.<br />Competing Interests: The authors have declared that no competing interests exist.
- Subjects :
- Animals
Bacterial Proteins metabolism
Borrelia burgdorferi genetics
Borrelia burgdorferi immunology
Disease Models, Animal
Disease Vectors
High-Throughput Nucleotide Sequencing
Host-Pathogen Interactions
Lyme Disease immunology
Mice
Ticks microbiology
Virulence Factors metabolism
Bacterial Proteins genetics
Borrelia burgdorferi growth & development
DNA Transposable Elements
Gene Expression Regulation, Bacterial
Lyme Disease microbiology
Ticks growth & development
Virulence Factors genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1553-7374
- Volume :
- 15
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- PLoS pathogens
- Publication Type :
- Academic Journal
- Accession number :
- 31086414
- Full Text :
- https://doi.org/10.1371/journal.ppat.1007644