Bordetella pertussis, a strictly human re-emerging pathogen and the causative agent of whooping cough, exploits a broad variety of virulence factors to establish efficient infection. Here, we used RNA sequencing to analyse the changes in gene expression profiles of human THP-1 macrophages resulting from B. pertussis infection. In parallel, we attempted to determine the changes in intracellular B. pertussis-specific transcriptomic profiles resulting from interaction with macrophages. Our analysis revealed that global gene expression profiles in THP-1 macrophages are extensively rewired 6 h post-infection. Among the highly expressed genes, we identified those encoding cytokines, chemokines, and transcription regulators involved in the induction of the M1 and M2 macrophage polarization programmes. Notably, several host genes involved in the control of apoptosis and inflammation which are known to be hijacked by intracellular bacterial pathogens were overexpressed upon infection. Furthermore, in silico analyses identified large temporal changes in expression of specific gene subsets involved in signalling and metabolic pathways. Despite limited numbers of the bacterial reads, we observed reduced expression of majority of virulence factors and upregulation of several transcriptional regulators during infection suggesting that intracellular B. pertussis cells switch from virulent to avirulent phase and actively adapt to intracellular environment, respectively.

Division of Cell and Developmental Biology Medical University of Vienna Vienna Austria

Facultad de Ciencias Exactas Universidad Nacional de La Plata CINDEFI La Plata Argentina

Faculty of Computer Science Research Group Bioinformatics and Computational Biology University of Vienna Vienna Austria

Institute for Theoretical Chemistry University of Vienna Vienna Austria

Institute of Microbiology of the Czech Academy of Sciences Laboratory of Molecular Biology of Bacterial Pathogens Prague Czech Republic

Institute of Microbiology of the Czech Academy of Sciences Laboratory of Post transcriptional Control of Gene Expression Prague Czech Republic

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RNA Biol. 2020 Oct;17(10):1520. doi: 10.1080/15476286.2020.1776981. PubMed

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An IS element-driven antisense RNA attenuates the expression of serotype 2 fimbriae and the cytotoxicity of Bordetella pertussis

T3SS chaperone of the CesT family is required for secretion of the anti-sigma factor BtrA in Bordetella pertussis

Avirulent phenotype promotes Bordetella pertussis adaptation to the intramacrophage environment

Omics Analysis of Blood-Responsive Regulon in Bordetella pertussis Identifies a Novel Essential T3SS Substrate

A Mutation Upstream of the rplN-rpsD Ribosomal Operon Downregulates Bordetella pertussis Virulence Factor Production without Compromising Bacterial Survival within Human Macrophages

Bordetella Type III Secretion Injectosome and Effector Proteins