Dataset Information

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.

SUBMITTER: Hammamieh R

PROVIDER: S-EPMC4803270 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Temporal Progression of Pneumonic Plague in Blood of Nonhuman Primate: A Transcriptomic Analysis.

Hammamieh Rasha R Muhie Seid S Borschel Richard R Gautam Aarti A Miller Stacy-Ann SA Chakraborty Nabarun N Jett Marti M

PloS one 20160322 3

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 ...[more]

PMID: 27003632

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Project description:transcriptomic analyses showed there was a very rapid proliferation of Y. pestis in assault on African green monkeys. The bacterial loads were enumerated in the blood at delayed time points supporting earlier observations (Layton et al., 2011). Interpretation of transcriptomic changes reveals that the host defense has been essentially shattered, and the process of multi-organ failure was initiated one day after inhalation exposure. At 24 h post-exposure, the diseased animals were possibly at the middle of their survival curves. Hence, such molecular indicators could have critical therapeutic values, particularly when therapies fail to intervene at the earliest opportunity. In the early phase of pathogenesis, systematic reprogramming of both adaptive and innate immunity programs is mediated, leading to sepsis. Results suggest the possibility of early molecular perturbations in the lungs and muscle tissues, and catabolic related activities, such as biosynthesis. Apoptosis ensued at the early stage, which potentially became rapid by recruiting an increasing number of apoptotic networks. Beyond 24 h, rapid apoptosis could have acted in concert with hypercytokinemia and hyperchemokinemia, resulting in failures of many peripheral organs. Following a published report (Layton et al., 2011), the present study was designed to expose the nonhuman primates with a target dose of 100 Â± 50 ED50 aerosolized Y. pestis strain CO92 under ABSL-3 conditions. Seventy-two hours prior to aerosol exposure, all animals were moved into the ABSL-3 for acclimatization. As described in Figure S1, initial blood draws were carried out 24 h before Y. pestis aerosol challenge. The animals were challenged via aerosol with 1 x 106 virulent organisms while under anesthesia with 4 mg/kg Telazol (Fort Dodge Animal Health, Fort Dodge, IA). Post-exposure clinical illness and disseminated infection were evaluated by direct clinical observations. All animals within each group were exposed on the same day at 30 minute intervals, and subsequent blood draws were conducted at 45 m, 6 h, 9 h, 12 h, 18 h, 24 h, 32 h and 42 h.

Dataset Information

Temporal Progression of Pneumonic Plague in Blood of Nonhuman Primate: A Transcriptomic Analysis.

Publications

Temporal Progression of Pneumonic Plague in Blood of Nonhuman Primate: A Transcriptomic Analysis.

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