Regulated, sequential processing by multiple proteases is required for proper maturation and release of Bordetella filamentous hemagglutinin.

Abstract:

:Filamentous hemagglutinin (FHA) is a critically important virulence factor produced by Bordetella species that cause respiratory infections in humans and other animals. It is also a prototypical member of the widespread two partner secretion (TPS) pathway family of proteins. First synthesized as a ~370 kDa protein called FhaB, its C-terminal ~1,200 amino acid 'prodomain' is removed during translocation to the cell surface via the outer membrane channel FhaC. Here, we identify CtpA as a periplasmic protease that is responsible for the regulated degradation of the prodomain and for creation of an intermediate polypeptide that is cleaved by the autotransporter protease SphB1 to generate FHA. We show that the central prodomain region is required to initiate degradation of the prodomain and that CtpA degrades the prodomain after a third, unidentified protease (P3) first removes the extreme C-terminus of the prodomain. Stepwise proteolysis by P3, CtpA and SphB1 is required for maturation of FhaB, release of FHA into the extracellular milieu, and full function in vivo. These data support a substantially updated model for the mechanism of secretion, maturation and function of this model TPS protein.

journal_name

Mol Microbiol

journal_title

Molecular microbiology

authors

Nash ZM,Cotter PA

doi

10.1111/mmi.14318

subject

Has Abstract

pub_date

2019-09-01 00:00:00

pages

820-836

issue

3

eissn

0950-382X

issn

1365-2958

journal_volume

112

pub_type

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