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Open AccessArticle

Common Host Responses in Murine Aerosol Models of Infection Caused by Highly Virulent Gram-Negative Bacteria from the Genera Burkholderia, Francisella and Yersinia

1
Chemical, Biological and Radiological Division, DSTL Porton Down, Salisbury SP4 0JQ, UK
2
Biosciences, University of Exeter, Geoffrey Pope Building, Stocker Road, Exeter EX4 4QD, UK
*
Author to whom correspondence should be addressed.
Pathogens 2019, 8(4), 159; https://doi.org/10.3390/pathogens8040159
Received: 21 June 2019 / Revised: 6 September 2019 / Accepted: 18 September 2019 / Published: 21 September 2019
Highly virulent bacterial pathogens cause acute infections which are exceptionally difficult to treat with conventional antibiotic therapies alone. Understanding the chain of events that are triggered during an infection of a host has the potential to lead to new therapeutic strategies. For the first time, the transcriptomic responses within the lungs of Balb/C mice have been compared during an acute infection with the intracellular pathogens Burkholderia pseudomallei, Francisella tularensis and Yersinia pestis. Temporal changes were determined using RNAseq and a bioinformatics pipeline; expression of protein was also studied from the same sample. Collectively it was found that early transcriptomic responses within the infected host were associated with the (a) slowing down of critical cellular functions, (b) production of circulatory system components, (c) lung tissue integrity, and (d) intracellular regulatory processes. One common molecule was identified, Errfi1 (ErbB receptor feedback inhibitor 1); upregulated in response to all three pathogens and a potential novel marker of acute infection. Based upon the pro-inflammatory responses observed, we sought to synchronise each infection and report that 24 h p.i. of B. pseudomallei infection closely aligned with 48 h p.i. of infection with F. tularensis and Y. pestis. Post-transcriptional modulation of RANTES expression occurred across all pathogens, suggesting that these infections directly or indirectly modulate cell trafficking through chemokine expression/detection. Collectively, this unbiased NGS approach has provided an in-depth characterisation of the host transcriptome following infection with these highly virulent pathogens ultimately aiding in the development of host-directed therapies as adjuncts or alternatives to antibiotic treatment. View Full-Text
Keywords: RNAseq; pulmonary; infection; melioidosis; tularemia; plague; respiratory RNAseq; pulmonary; infection; melioidosis; tularemia; plague; respiratory
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Clark, G.C.; Essex-Lopresti, A.; Moore, K.A.; Williamson, E.D.; Lukaszewski, R.; Paszkiewicz, K.; David, J. Common Host Responses in Murine Aerosol Models of Infection Caused by Highly Virulent Gram-Negative Bacteria from the Genera Burkholderia, Francisella and Yersinia. Pathogens 2019, 8, 159.

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