Sweet life: what the antibiotic rifampicin and sugars have in common

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F24%3A00599273" target="_blank" >RIV/61388971:_____/24:00599273 - isvavai.cz</a>

Result on the web

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DOI - Digital Object Identifier

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Result language

angličtina

Original language name

Sweet life: what the antibiotic rifampicin and sugars have in common

Original language description

Filamentous hemagglutinin (FHA), a major virulence factor of classical Bordetellae, is a rod-shaped molecule that nplays an important role in the adherence of bacteria to ciliated epithelial cells of the upper respiratory tract and suppresses nthe host innate and adaptive immune response. FHA is translated as a 360-kDa FhaB precursor that is exported nacross the outer bacterial membrane by a two-partner secretion mechanism involving the outer membrane protein nFhaC and shed into external environment as an N-terminal ‘mature’ 220-kDa FHA protein after processing by surface exposed SphB1 protease. The remaining C-terminal 130-kDa FhaB prodomain is thought to regulate maturation process and nrapidly degraded in the periplasm. We show here that both the extreme C terminus (ECT) of the FhaB prodomain and the nmature FHA play the pivotal roles in the virulence of B. pertussis. The NMR-based structural analysis of ECT, na highly-conserved the C-terminal 100 residues of the FhaB precursor, revealed that the ECT polypeptide adopts a rigid nstructure with a ‘pilin-like’ protein fold. Deletion of the sequence encoding ECT (ΔECT) resulted in a significant ndecrease in bacterial colonization within the nasal cavity of infected mice, comparable to B. pertussis strain lacking the nFhaB precursor (ΔFhaB). Intriguingly, the ΔECT strain exhibited a complete loss of its ability to bind cilia on human nnasal epithelial cells grown at the air-liquid interface, emphasizing the indispensable role of ECT in the adherence nof Bordetella cells to ciliated epithelial cells. Furthermore, we demonstrate the mature FHA confers resistance of nB. pertussis to complement-mediated killing, highlighting its involvement in protection of bacterial cells against the host’s ninnate immune response. Collectively, these results provide novel insights into FHA biology, unraveling its multifaceted nrole in the virulence of pathogenic Bordetellae.

Czech name

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Czech description

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Type

O - Miscellaneous

CEP classification

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OECD FORD branch

10606 - Microbiology

Project

<a href="/en/project/LX22NPO5103" target="_blank" >LX22NPO5103: National Institute of Virology and Bacteriology</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2024

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů