Avirulent phenotype promotes Bordetella pertussis adaptation to the intramacrophage environment

0567327 - MBÚ 2024 RIV GB eng J - Journal Article
Farman, M.R. - Petráčková, Denisa - Kumar, Dilip - Držmíšek, Jakub - Saha, Argha - Čurnová, Lenka - Čapek, Jan - Hejnarová, Václava - Amman, F. - Hofacker, I. - Večerek, Branislav
Avirulent phenotype promotes Bordetella pertussis adaptation to the intramacrophage environment.
Emerging Microbes & Infections. Roč. 12, č. 1 (2023), č. článku e2146536. E-ISSN 2222-1751
R&D Projects: GA ČR(CZ) GA23-05634S; GA MŠMT(CZ) LX22NPO5103
Institutional support: RVO:61388971
Keywords : Bordetella pertussis * BvgAS * intramacrophage environment * adaptation to stress * cysteine toxicity * avirulent phase
OECD category: Microbiology
Impact factor: 13.2, year: 2022
Method of publishing: Open access
https://www.tandfonline.com/doi/full/10.1080/22221751.2022.2146536

Bordetella pertussis, the causative agent of whooping cough, is an extracellular, strictly human pathogen. However, it hasbeen shown thatB. pertussiscells can escape phagocytic killing and survive in macrophages upon internalization. Ourtime-resolved RNA-seq data suggest thatB. pertussisefficiently adapts to the intramacrophage environment andresponds to host bactericidal activities. We show that this adaptive response is multifaceted and, surprisingly, relatedto the BvgAS two-component system, a master regulator of virulence. Our results show that the expression of thisregulatory circuit is downregulated upon internalization. Moreover, we demonstrate that the switch to the avirulentBvg−phase augments a very complex process based on the adjustment of central and energy metabolism, cell wallreinforcement, maintenance of appropriate redox and metal homeostasis, and repair of damaged macromolecules.Nevertheless, not all observed effects could be simply attributed to the transition to Bvg−phase, suggesting thatadditional regulators are involved in the adaptation to the intramacrophage environment. Interestingly, a largenumber of genes required for the metabolism of sulphur were strongly modulated within macrophages. In particular,the mutant lacking two genes encoding cysteine dioxygenases displayed strongly attenuated cytotoxicity towardTHP-1 cells. Collectively, our results suggest that intracellularB. pertussiscells have adopted the Bvg−mode toacclimate to the intramacrophage environment and respond to antimicrobial activities elicited by THP-1 cells.Therefore, we hypothesize that the avirulent phase represents an authentic phenotype of internalizedB. pertussiscells.
Permanent Link: https://hdl.handle.net/11104/0338590