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Avirulent phenotype promotes Bordetella pertussis adaptation to the intramacrophage environment
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SYSNO ASEP 0567327 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Avirulent phenotype promotes Bordetella pertussis adaptation to the intramacrophage environment Tvůrce(i) Farman, M.R. (AT)
Petráčková, Denisa (MBU-M) RID, ORCID
Kumar, Dilip (MBU-M) ORCID
Držmíšek, Jakub (MBU-M) ORCID
Saha, Argha (MBU-M)
Čurnová, Lenka (MBU-M)
Čapek, Jan (MBU-M) ORCID
Hejnarová, Václava (MBU-M)
Amman, F. (AT)
Hofacker, I. (AT)
Večerek, Branislav (MBU-M) RID, ORCIDČíslo článku e2146536 Zdroj.dok. Emerging Microbes & Infections . - : Nature Publishing Group
Roč. 12, č. 1 (2023)Poč.str. 16 s. Jazyk dok. eng - angličtina Země vyd. GB - Velká Británie Klíč. slova Bordetella pertussis ; BvgAS ; intramacrophage environment ; adaptation to stress ; cysteine toxicity ; avirulent phase Vědní obor RIV EE - Mikrobiologie, virologie Obor OECD Microbiology CEP GA23-05634S GA ČR - Grantová agentura ČR LX22NPO5103 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Způsob publikování Open access Institucionální podpora MBU-M - RVO:61388971 UT WOS 000915927900001 EID SCOPUS 85146652721 DOI 10.1080/22221751.2022.2146536 Anotace 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. Pracoviště Mikrobiologický ústav Kontakt Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231 Rok sběru 2024 Elektronická adresa https://www.tandfonline.com/doi/full/10.1080/22221751.2022.2146536
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