title: Dermacentor andersoni transmission of Francisella tularensis subsp. novicida reflects bacterial colonization, dissemination, and replication coordinated with tick feeding.
abstract: Ticks serve as biological vectors for a wide variety of bacterial pathogens which must be able to efficiently colonize specific tick tissues prior to transmission. The bacterial determinants of tick colonization are largely unknown, a knowledge gap attributed in large part to the paucity of tools to genetically manipulate these pathogens. In this study, we demonstrated that Francisella tularensis subsp. novicida, for which a complete two-allele transposon mutant library has been constructed, initially infects the midguts of 100% of acquisition-fed Dermacentor andersoni nymphs, with stable colonization and replication during a subsequent molt. Increased dissemination to and marked replication within the salivary gland was closely linked to a second (transmission) feed and culminated in secretion of bacteria into the saliva and successful transmission. Simultaneous testing of multiple mutants resulted in total bacterial levels similar to those observed for single mutants. However, there was evidence of a bottleneck during colonization, resulting in a founder effect in which the most successful mutant varied when comparing individual ticks. Thus, it is essential to assess mutant success at the level of the tick population rather than in individual ticks. The ability of F. tularensis subsp. novicida to recapitulate the key physiological events by which bacteria colonize and are transmitted by ixodid ticks provides a new genome-wide approach to identify the required pathogen molecules and pathways. The identification of specific genes and, more importantly, conserved pathways that function at the tick-pathogen interface will accelerate the development of new methods to block transmission.
authors.affiliation: Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164-7040, USA. kreif@vetmed.wsu.edu
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Reif
authors.forename: Guy H
authors.initials: GH
authors.lastname: Palmer
authors.forename: Massaro W
authors.initials: MW
authors.lastname: Ueti
authors.forename: Glen A
authors.initials: GA
authors.lastname: Scoles
authors.forename: J J
authors.initials: JJ
authors.lastname: Margolis
authors.forename: D M
authors.initials: DM
authors.lastname: Monack
authors.forename: Susan M
authors.initials: SM
authors.lastname: Noh
mesh_terms: D000818:Animals; D001096:Arachnid Vectors / Q000382:microbiology* / Q000502:physiology; D002688:Chitinases / Q000235:genetics; D003870:Dermacentor / Q000382:microbiology* / Q000502:physiology; D005247:Feeding Behavior / Q000502:physiology; D005260:Female; D005604:Francisella tularensis / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009758:Nymph / Q000382:microbiology / Q000502:physiology; D011817:Rabbits; D014406:Tularemia / Q000382:microbiology / Q000635:transmission*
chemical_list: D002688:Chitinases