title: Stage-specific global alterations in the transcriptomes of Lyme disease spirochetes during tick feeding and following mammalian host adaptation.
abstract: Borrelia burgdorferi, the agent of Lyme disease, is maintained in nature within an enzootic cycle involving a mammalian reservoir and an Ixodes sp. tick vector. The transmission, survival and pathogenic potential of B. burgdorferi depend on the bacterium's ability to modulate its transcriptome as it transits between vector and reservoir host. Herein, we employed an amplification-microarray approach to define the B. burgdorferi transcriptomes in fed larvae, fed nymphs and in mammalian host-adapted organisms cultivated in dialysis membrane chambers. The results show clearly that spirochetes exhibit unique expression profiles during each tick stage and during cultivation within the mammal; importantly, none of these profiles resembles that exhibited by in vitro grown organisms. Profound shifts in transcript levels were observed for genes encoding known or predicted lipoproteins as well as proteins involved in nutrient uptake, carbon utilization and lipid synthesis. Stage-specific expression patterns of chemotaxis-associated genes also were noted, suggesting that the composition and interactivities of the chemotaxis machinery components vary considerably in the feeding tick and mammal. The results as a whole make clear that environmental sensing by B. burgdorferi directly or indirectly drives an extensive and tightly integrated modulation of cell envelope constituents, chemotaxis/motility machinery, intermediary metabolism and cellular physiology. These findings provide the necessary transcriptional framework for delineating B. burgdorferi regulatory pathways throughout the enzootic cycle as well as defining the contribution(s) of individual genes to spirochete survival in nature and virulence in humans.
authors.affiliation: Department of Microbiology and Immunology, New York Medical College, Valhalla, NY, USA.
authors.forename: Radha
authors.initials: R
authors.lastname: Iyer
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Caimano
authors.forename: Amit
authors.initials: A
authors.lastname: Luthra
authors.forename: David
authors.initials: D
authors.lastname: Axline
authors.forename: Arianna
authors.initials: A
authors.lastname: Corona
authors.forename: Dumitru A
authors.initials: DA
authors.lastname: Iacobas
authors.forename: Justin D
authors.initials: JD
authors.lastname: Radolf
authors.forename: Ira
authors.initials: I
authors.lastname: Schwartz
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D025065:Borrelia burgdorferi / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity / Q000502:physiology; D050260:Carbohydrate Metabolism / Q000235:genetics; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D002473:Cell Wall / Q000378:metabolism; D002633:Chemotaxis / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D018884:Ixodes / Q000254:growth & development / Q000382:microbiology*; D007814:Larva / Q000382:microbiology; D008018:Life Cycle Stages / Q000235:genetics; D008193:Lyme Disease / Q000382:microbiology*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D008809:Mice, Inbred C3H; D009758:Nymph / Q000382:microbiology; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D012808:Sigma Factor / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome
chemical_list: D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; D012808:Sigma Factor; C069567:sigma factor KatF protein, Bacteria