Question

Bordetella pertussis, the bacterial species that causes Whooping cough, has several virulence factors. They include: Filamentous Hemagglutinin (an adhesin), Fimbriae, Pertussis toxin, and Tracheal cytotoxin. Based on what you know about how infections work, what are the roles of these virulence factors? Which are defensive and which are offensive? (you do not have to identify exactly what each of these virulence factors do – but identify what kind of virulence factor they are).

Answer 1

Bordetella pertussis is a Gram-negative, aerobic, pathogenic, encapsulated coccobacillus of the genus Bordetella, and the causative agent of pertussis or whooping cough.

virulence factors include adhesins such as filamentous haemagglutinin, fimbriae and pertactin, which allow B. pertussis to bind to ciliated epithelial cells in the upper respiratory tract. Once attachment is initiated, toxins produced by the bacterium enable colonisation to proceed by interfering with host clearance mechanisms. B. pertussis co-ordinately regulates the expression of virulence factors via the Bordetella virulence gene (bvg) locus, which encodes a response regulator responsible for signal-mediated activation and repression. This strict regulation mechanism allows the bacterium to express different gene subsets in different environmental niches within the host, according to the stage of disease progression.

Pertussis toxin is a secreted protein exotoxin and an important virulence factor produced exclusively by B. Pertussis. PT is transported across the bacterial outer membrane by a type IV secretion system encoded by the ptl genes, which are located downstream from the ptx genes encoding the toxin. PT is a complex multisubunit toxin with an AB5 configuration (one active subunit plus five binding subunits). The B oligomer is a pentameric ring composed of subunits S2, S3, two S4, and S5, which bind to various (but mostly unidentified) glycoconjugate molecules on the surface of target cells. S2 and S3 each contain two different carbohydrate-binding domains, which most likely accounts for the capacity of PT to bind to and intoxicate virtually any mammalian cell (at least in culture). The enzymatic activity of PT resides in the A subunit, also known as S1. Once in the cell cytosol, S1 hydrolyzes cellular NAD and transfers the released ADP-ribose to a specific cysteine residue near the C-terminus of the α subunit of heterotrimeric G-proteins of the Gi family in mammalian cells.

Adenylate cyclase toxin is another important virulence factor secreted by B. pertussis (and also by other closely related Bordetella species). It is an immunogenic protein and can elicit a protective immune response.ACT is secreted from B. pertussis by a type I secretion ‘channel-tunnel’ mechanism formed by the CyaBDE proteins, and is then modified by fatty acylation on two specific lysine residues in the hemolysin domain mediated by the CyaC acyltransferase. Most of the secreted toxin appears to remain associated with the bacterial cell surface through an interaction with the bacterial adherence factor filamentous hemagglutinin, but this toxin is not active. Instead, newly synthesized and secreted ACT is the active form of the toxin.