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.

Airborne bioaerosols and their impact on human health

“…Pneumonic plague is another deadly infectious and transmittable disease when fine infective droplets are inhaled (Hammamieh et al, 2016). A total of 21,725 cases of human plague were reported globally during 2000 to 2009 including 1612 deaths (Butler, 2013).…”

Quantification of Viable Bioaerosol Emanation from an ACMV System and its Impact on Indoor Bioaerosol Pollution

“…Bioaerosol, especially airborne bacteria and fungi, is an important concern for indoor environments (Lal et al, 2017). Human exposure to airborne bacteria and fungi can lead to serious infectious diseases (Cole and Cook, 1998;Daniels et al, 2016;Fan et al, 2017;Kim et al, 2017) such as Legionnaires' disease (Berrington and Hawn, 2013), tuberculosis (TB) (Pedersen et al, 2016) and pneumonic plague (Hammamieh et al, 2016). In addition, some allergens such as spores and hyphae (Jutel et al, 2016), which can cause serious respiratory diseases (Hargreaves et al, 2003;Vesper et al, 2008;Beck et al, 2012 ;Du et al, 2018), are found in indoor bioaerosols.…”

iMarmot: an integrative platform for comparative and functional genomics of marmots

“…Meanwhile, our group has assembled and published the genome sequence of the Himalayan marmot (Marmota himalayana) and resequenced the whole genomes of another four marmots, including Mongolia marmot (Marmota sibirica), Gray marmot (Marmota baibacina), Long-tailed marmot (Marmota caudata) and Yellow-bellied marmot in 2019 [10]. Particularly, RNA-seq or microarray data from a broad range of mammal hibernators and plague hosts provide novel insight into understanding the special biological features of marmots, especially the molecular mechanism of hibernation [10][11][12][13][14][15][16]. However, there is no available database to save, exploit, analyze and distribute these largescale datasets.…”