title: Temporal Progression of Pneumonic Plague in Blood of Nonhuman Primate: A Transcriptomic Analysis.
abstract: Early identification of impending illness during widespread exposure to a pathogenic agent offers a potential means to initiate treatment during a timeframe when it would be most likely to be effective and has the potential to identify novel therapeutic strategies. The latter could be critical, especially as antibiotic resistance is becoming widespread. In order to examine pre-symptomatic illness, African green monkeys were challenged intranasally with aerosolized Yersinia pestis strain CO92 and blood samples were collected in short intervals from 45 m till 42 h post-exposure. Presenting one of the first genomic investigations of a NHP model challenged by pneumonic plague, whole genome analysis was annotated in silico and validated by qPCR assay. Transcriptomic profiles of blood showed early perturbation with the number of differentially expressed genes increasing until 24 h. By then, Y. pestis had paralyzed the host defense, as suggested by the functional analyses. Early activation of the apoptotic networks possibly facilitated the pathogen to overwhelm the defense mechanisms, despite the activation of the pro-inflammatory mechanism, toll-like receptors and microtubules at the port-of-entry. The overexpressed transcripts encoding an early pro-inflammatory response particularly manifested in active lymphocytes and ubiquitin networks were a potential deviation from the rodent models, which needs further verification. In summary, the present study recognized a pattern of Y. pestis pathogenesis potentially more applicable to the human system. Independent validation using the complementary omics approach with comprehensive evaluation of the organs, such as lungs which showed early bacterial infection, is essential.
authors.affiliation: US Army Center for Environmental Health Research, Fort Detrick, Maryland, 21702-5010, United States of America.
authors.forename: Rasha
authors.initials: R
authors.lastname: Hammamieh
authors.affiliation: US Army Center for Environmental Health Research, Fort Detrick, Maryland, 21702-5010, United States of America.|Advanced Biomedical Center, Fredrick National Lab for Cancer Research, National Cancer Institute, Fredrick, Maryland, 21702, United States of America.
authors.forename: Seid
authors.initials: S
authors.lastname: Muhie
authors.affiliation: Walter Reed Army Medical Center, Silver Spring, Maryland, 20910, United States of America.
authors.forename: Richard
authors.initials: R
authors.lastname: Borschel
authors.affiliation: US Army Center for Environmental Health Research, Fort Detrick, Maryland, 21702-5010, United States of America.|The Geneva Foundation, Fort Detrick, Maryland, 21702-5010, United States of America.
authors.forename: Aarti
authors.initials: A
authors.lastname: Gautam
authors.affiliation: US Army Center for Environmental Health Research, Fort Detrick, Maryland, 21702-5010, United States of America.|The Geneva Foundation, Fort Detrick, Maryland, 21702-5010, United States of America.
authors.forename: Stacy-Ann
authors.initials: SA
authors.lastname: Miller
authors.affiliation: US Army Center for Environmental Health Research, Fort Detrick, Maryland, 21702-5010, United States of America.|The Geneva Foundation, Fort Detrick, Maryland, 21702-5010, United States of America.
authors.forename: Nabarun
authors.initials: N
authors.lastname: Chakraborty
authors.affiliation: US Army Center for Environmental Health Research, Fort Detrick, Maryland, 21702-5010, United States of America.
authors.forename: Marti
authors.initials: M
authors.lastname: Jett
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D000818:Animals; D002522:Chlorocebus aethiops; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D018450:Disease Progression; D020869:Gene Expression Profiling; D007113:Immunity, Innate / Q000276:immunology; D008168:Lung / Q000473:pathology; D008297:Male; D008992:Monkey Diseases / Q000276:immunology* / Q000382:microbiology; D010930:Plague / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction; D037521:Virulence Factors / Q000235:genetics; D015010:Yersinia pestis / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*
chemical_list: D016207:Cytokines; D037521:Virulence Factors