title: Transit through the flea vector induces a pretransmission innate immunity resistance phenotype in Yersinia pestis.
abstract: Yersinia pestis, the agent of plague, is transmitted to mammals by infected fleas. Y. pestis exhibits a distinct life stage in the flea, where it grows in the form of a cohesive biofilm that promotes transmission. After transmission, the temperature shift to 37 degrees C induces many known virulence factors of Y. pestis that confer resistance to innate immunity. These factors are not produced in the low-temperature environment of the flea, however, suggesting that Y. pestis is vulnerable to the initial encounter with innate immune cells at the flea bite site. In this study, we used whole-genome microarrays to compare the Y. pestis in vivo transcriptome in infective fleas to in vitro transcriptomes in temperature-matched biofilm and planktonic cultures, and to the previously characterized in vivo gene expression profile in the rat bubo. In addition to genes involved in metabolic adaptation to the flea gut and biofilm formation, several genes with known or predicted roles in resistance to innate immunity and pathogenicity in the mammal were upregulated in the flea. Y. pestis from infected fleas were more resistant to phagocytosis by macrophages than in vitro-grown bacteria, in part attributable to a cluster of insecticidal-like toxin genes that were highly expressed only in the flea. Our results suggest that transit through the flea vector induces a phenotype that enhances survival and dissemination of Y. pestis after transmission to the mammalian host.
authors.affiliation: Laboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.
authors.forename: Viveka
authors.initials: V
authors.lastname: Vadyvaloo
authors.forename: Clayton
authors.initials: C
authors.lastname: Jarrett
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Sturdevant
authors.forename: Florent
authors.initials: F
authors.lastname: Sebbane
authors.forename: B Joseph
authors.initials: BJ
authors.lastname: Hinnebusch
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D018441:Biofilms; D015870:Gene Expression; D020869:Gene Expression Profiling; D005798:Genes, Bacterial; D007113:Immunity, Innate / Q000235:genetics*; D007303:Insect Vectors / Q000235:genetics* / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D005423:Siphonaptera / Q000469:parasitology*; D015010:Yersinia pestis / Q000472:pathogenicity* / Q000502:physiology*