BORDETELLA PERTUSSIS Flashcards
- What are possible reasons for the recent increase in the incidence of B.pertussis infections ?
- Strain evolution in circulating B. pertussis strains. In some strains, antigens included in acellular vaccines are lost or changed its Aa sequence and thus probably immunogenicity, or expressed at very low levels. It seems that strains adapt to vaccines to avoid the expression of these vaccines components.
- Waning immunity after vaccination with acellular vaccines, more booster vaccinations will be then needed to be protected again.
- Acellular vaccines prevent from symptoms but not from colonization, thus, there may exist a large reservoir of resident bacteria in the population.
- Low immunization rates among adolescents and adults (the infected adults are a reservoir).
- Also improvement in diagnostics and surveillance may play a very important role
- The rise of new Bordetella species causing whooping cough like symptoms
Thing to remember: acellular vaccines were developed based on purified protective antigens and introduced for general use in the past two decades
- Which are the major antigens used in modern acellular vaccines against whooping cough?
Filamentous Hemagglutinin (FHA), fimbriae (FIM), pertactin (PRN) and Pertusiss toxin (PTX).
- Why is whooping cough frequently not diagnosed early enough for antibiotics therapy?
The symptoms for whooping cough appear after several days (10-14 days) but bacteria can only be detected within 2weeks of infection. this makes early diagnosis difficult. Early symptoms are nonspecific.
- Please describe the major properties of the adenylate cyclase toxin of B.pertussis.
It belongs to the family of RTX family. It is a family of toxins which have common structures and features. It is secreted by the type I secretion system. It is also chemically modified by acylation of lysine residues (palmitoylation. It also increases the cAMP levels in the cell. It can also form pores in the target cell. Therefore it is haemolytic on agar plates. CYA is a protective antigen.
It has two functional domains. It has a C-terminal domain with repeats mediating receptor binding and pore formation in cell membrane and a N-terminal domain with a calmodulin-dependent adenylate cyclase invades eukaryotic cells leading to cAMP formation.
CYA blocks complement-dependent phagocytosis by macrophages and suppresses activation and chemotaxis of T-cells, however, the in vivo relevance of these data is unclear. It binds mainly to neutrophils, dendritic cells and macrophages
Slide 18.
- Please describe the chemical composition of the tracheal cytotoxin of B.pertussis and its presumed role in virulence!
It is a muramyl peptide is generated during normal cell wall remodelling and usually is recylced by transport into the cytosol via the AmpG transport protein.
In B. pertussis the expression of the ampG gene is very low and TCT accumulates in the periplasm and is released in the medium. TCT is the only known dedicated virulence factor of B. pertussis that is not regulated by the BvgAS system.
In hamster tracheal rings it was shown that TCT synergistically with lipooligosaccharide (LOS) stimulates production of proinflammatory cytokines (TNFa, IL-1a, IL-1b, IL-6) and induces nitric oxide synthase (iNOS).
Production of NO results in tissue destruction and extrusion of ciliated cells from the epithelial surface (hamster tracheal rings); see image on the right. The contribution of TCT to pertussis pathogenesis is unclear.
They colonize epithelial cells, cause cell blebbing and release of epithelial cells.
- Which cell type is the major target for adhesion and colonization by B.pertussis?
Cilliated epithelial cells in the upper respiratory tract (trachea).
- Please describe briefly how expression of most virulence genes is regulated in B.pertussis
A transmembrane protein with a periplasmic sensory or input domain and a cytoplasmic histidine kinase domain perceives a stimulus. This signal is transferred to the cytoplasmic portion of the protein via conformational changes and leads to autophosphorylation at a histidine residue. The phosphate is then transferred to the second protein, a response regulator, which is phosphorylated at an aspartate in its so-called receiver domain. This leads to a conformational change activating the second domain, the output or effector domain. This domain most frequently harbours a DNA-binding motif enabling the protein to act as a positive or negative transcription factor. The output domain may also harbour alternative activities including enzymatic activities which are regulated by phosphorylation of the protein.
- Which groups of genes can be classified according to their BvgAS-mediated expression pattern and provide examples for each group?
- Class 4 these genes comprise the vrg genes
- Class 1 these genes are expressed late after Removing modulating conditions
- Class2 these genes are tuned on quickly after Removing modulating conditions
- Class 3: these genes are tuned on quickly after
Removing modulating conditions but are turned off when Class 1 genes start to be expressed - Class 1 late PTX and CYA (immune modulation…)
- Class 2 early FHA, FIM adherence
- Class 3 intermediate BipA transmission
- Class 4 vrg genes required for survival outside of the host?
Since B pertussis can not survive outside Of the human host they may be an evolutionary relic of an ancestor
The amount of phosphorylated BvgA response regulator is decisive which class of genes is expressed
- Compare briefly some important genomic properties of the classical Bordetellae.
Classical bordetellae B.bronchiseptica, B.parapertussis and B.pertussis.
The species B.pertussis and B.parapertussis which independently have evolved rom a B.bronchiseptica–like ancestors how interesting features which clearly indicate that they are still under selective evolutionary pressure. Both have much smaller genomes than B.bronchiseptica and, accordingly, a smaller number of genes. Both have a very high number of pseudogenes and both have a high number of transposable genetic elements. Thus, both species have probably started to specialize to a single host species relatively recently and still are in an ongoing state of genome erosion in which they get rid of genes not necessary anymor e or even disturbing. Mobile genetic elements may help in this process of genome reduction by causing genomic rearrangements and deletions.
- Please denominate three Bordetella species pathogenic for animals and which animals are infected by them
B. bronchiseptica: pigs, dogs, cats, seals, rabbits, horses, mice, sheep, humans
B. parapertussis: human, sheep
B. pertussis: humans
