title: RNA signatures allow rapid identification of pathogens and antibiotic susceptibilities.
abstract: With rising rates of drug-resistant infections, there is a need for diagnostic methods that rapidly can detect the presence of pathogens and reveal their susceptibility to antibiotics. Here we propose an approach to diagnosing the presence and drug-susceptibility of infectious diseases based on direct detection of RNA from clinical samples. We demonstrate that species-specific RNA signatures can be used to identify a broad spectrum of infectious agents, including bacteria, viruses, yeast, and parasites. Moreover, we show that the behavior of a small set of bacterial transcripts after a brief antibiotic pulse can rapidly differentiate drug-susceptible and -resistant organisms and that these measurements can be made directly from clinical materials. Thus, transcriptional signatures could form the basis of a uniform diagnostic platform applicable across a broad range of infectious agents.
authors.affiliation: The Broad Institute, Cambridge, MA 02142, USA.
authors.forename: Amy K
authors.initials: AK
authors.lastname: Barczak
authors.forename: James E
authors.initials: JE
authors.lastname: Gomez
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Kaufmann
authors.forename: Ella R
authors.initials: ER
authors.lastname: Hinson
authors.forename: Lisa
authors.initials: L
authors.lastname: Cosimi
authors.forename: Mark L
authors.initials: ML
authors.lastname: Borowsky
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Onderdonk
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Stanley
authors.forename: Devinder
authors.initials: D
authors.lastname: Kaur
authors.forename: Kevin F
authors.initials: KF
authors.lastname: Bryant
authors.forename: David M
authors.initials: DM
authors.lastname: Knipe
authors.forename: Alexander
authors.initials: A
authors.lastname: Sloutsky
authors.forename: Deborah T
authors.initials: DT
authors.lastname: Hung
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000145:classification / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D004912:Erythrocytes / Q000469:parasitology; D005658:Fungi / Q000145:classification / Q000187:drug effects / Q000235:genetics; D057809:HEK293 Cells; D006367:HeLa Cells; D018259:Herpesvirus 1, Human / Q000187:drug effects / Q000235:genetics; D018258:Herpesvirus 2, Human / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods*; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics; D012313:RNA / Q000235:genetics*; D015203:Reproducibility of Results; D013045:Species Specificity; D014556:Urine / Q000382:microbiology*
chemical_list: D000900:Anti-Bacterial Agents; D012313:RNA