The virulence factors ofBordetella pertussis: a matter of control

Abstract

Bordetella pertussis is the causative agent of whooping cough, a contagious childhood respiratory disease. Increasing public concern over the safety of whole-cell vaccines led to decreased immunisation rates and a subsequent increase in the incidence of the disease. Research into the development of safer, more efficacious, less reactogenic vaccine preparations was concentrated on the production and purification of detoxified B. pertussis virulence factors. These 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.

Comparative genomics of the classical Bordetella subspecies: the evolution and exchange of virulence-associated diversity amongst closely related pathogens

“…To examine the possible basis for differences in virulence phenotypes amongst strains/lineages, we compared the presence/absence of factors thought to be involved in interactions with the host, loosely referred to as “virulence factors”, including filamentous hemagglutinin (FHA), fimbriae (Fims), pertactin (PRN), tracheal colonization factor (TcfA), adenylate cyclase/hemolysin (ACT), dermonecrotic toxin (Dnt), pertussis toxin (Ptx), Bordetella resistance to killing (BrkA) protein [29], O-antigen [30], Type III secretion system (TTSS) [31], and Type VI secretion system (T6SS) [32]. Only genes encoding FHA, PRN, and TTSS locus are conserved in all strains (Figure 4).…”

“…Genes and the loci that encode the known virulence factors, filamentous haemagglutinin (FHA), fimbriae (Fims), pertactin (PRN), tracheal colonization factor (TcfA), invasive adenylate cyclase/haemolysin (ACT), dermonecrotic toxin (Dnt), pertussis toxin (Ptx), Bordetella resistance to killing (BrkA) [29], O-antigen [30], Type III secretion system (TTSS) [31], and Type VI secretion system (T6SS) [32], were compared among the eleven genomes via ACT [70]. Percent sequence similarity was calculated based on RB50 sequences with BLASTN [62], and genes that either contain a frame-shift mutation or an in-frame stop codon, or that are absent were highlighted with different colors in the heatmap that was generated by R [71].…”

Dynamics and Energy Contributions for Transport of Unfolded Pertactin through a Protein Nanopore

“…The translocation of the autotransporter passenger domain, which represents the mature virulence protein, across the bacterial outer membrane is mediated by its own cotranslated C-terminal transmembrane translocator domain and the folding properties of the passenger. ,, Pertactin is an extracellular integrin binding protein that mediates attachment of B. pertussis to the ciliated cells of the upper respiratory system . The pertactin passenger domain is 539 aa long and has a predicted net charge of −2.4 e at pH 7.5.…”

Pertussis Vaccines Scarcely Provide Protection against Bordetella parapertussis Infection in Children—A Systematic Review and Meta-Analysis

“…The acellular pertussis (aP) vaccines comprise major antigens such as PT and other components such as filamentous hemagglutinin (FHA), fimbrial antigens (FIM2, FIM3), and pertactin (PRN) [ 39 ]. Certain vaccines have shown protective efficacy against genetically related pathogens, as exemplified by BCG vaccination, which protects against Mycobacterium leprae and non-tuberculous mycobacteria [ 40 ]. The potential for pertussis vaccines to confer cross-protection against B. parapertussis remains debated.…”