Pertactin

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Pertactin
Pertactin1bad.png
Bordetella pertussis Virulence Factor P.69 Pertactin. PDB entry 1dab [1]
Identifiers
SymbolPRN
Pfam PF03212
InterPro IPR004899
PROSITE PDOC00271
SCOP2 1dab / SCOPe / SUPFAM
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary

In molecular biology, pertactin (PRN) is a highly immunogenic virulence factor of Bordetella pertussis , the bacterium that causes pertussis. Specifically, it is an outer membrane protein that promotes adhesion to tracheal epithelial cells. PRN is purified from Bordetella pertussis and is used for the vaccine production as one of the important components of acellular pertussis vaccine. [2]

A large part of the N-terminus of the pertactin protein is composed of beta helix repeats. [3] This region of the pertactin protein is secreted through the C-terminal autotransporter. The N-terminal signal sequences promotes the secretion of PRN into the periplasm through the bacterial secretion system (Sec) and consequently, the translocation into the outer membrane where it is proteolytically cleaved. [4] The loops in the right handed β-helix of the N-terminus that protrudes out of cell surface (region R1) contains sequence repeats Gly-Gly-Xaa-Xaa-Pro and the RGD domain Arg-Gly-Asp. [4] This RGD domain allows PRN to function as an adhesin and invasin, binding to integrins on the outer membrane of the cell. Another loop of the extending β-helix is region 2 (R2) which contains Pro-Gln-Pro (PQP) repeats towards the C-terminus. [4] This protein’s contribution to immunity is still premature. Reports suggest that R1 and R2 are immunogenic regions, however, recent studies regarding genetic variation of those regions prove otherwise.

In B.bronchiseptica

Pertactin adheres to only ciliated epithelial cells of B. bronchisepticain vivo. However, in vitro, PRN does not adhere to either. PRN does however help provide resistance towards a hyperinflammatory response of innate immunity for B. bronchiseptica. With respect to the adaptive immunity, studies show that PRN plays a role in combating neutrophil-mediated clearance of B. bronchiseptica. [4]

Related Research Articles

<span class="mw-page-title-main">Whooping cough</span> Human disease caused by the bacteria Bordetella pertussis

Whooping cough, also known as pertussis or the 100-day cough, is a highly contagious, vaccine-preventable bacterial disease. Initial symptoms are usually similar to those of the common cold with a runny nose, fever, and mild cough, but these are followed by two or three months of severe coughing fits. Following a fit of coughing, a high-pitched whoop sound or gasp may occur as the person breathes in. The violent coughing may last for 10 or more weeks, hence the phrase "100-day cough". The cough may be so hard that it causes vomiting, rib fractures, and fatigue. Children less than one year old may have little or no cough and instead have periods where they cannot breathe. The incubation period is usually seven to ten days. Disease may occur in those who have been vaccinated, but symptoms are typically milder.

<span class="mw-page-title-main">Exotoxin</span> Toxin from bacteria that destroys or disrupts cells

An exotoxin is a toxin secreted by bacteria. An exotoxin can cause damage to the host by destroying cells or disrupting normal cellular metabolism. They are highly potent and can cause major damage to the host. Exotoxins may be secreted, or, similar to endotoxins, may be released during lysis of the cell. Gram negative pathogens may secrete outer membrane vesicles containing lipopolysaccharide endotoxin and some virulence proteins in the bounding membrane along with some other toxins as intra-vesicular contents, thus adding a previously unforeseen dimension to the well-known eukaryote process of membrane vesicle trafficking, which is quite active at the host–pathogen interface.

<i>Bordetella bronchiseptica</i> Species of bacterium

Bordetella bronchiseptica is a small, gram-negative, rod-shaped bacterium of the genus Bordetella. It can cause infectious bronchitis in dogs and other animals, but rarely infects humans. Closely related to B. pertussis—the obligate human pathogen that causes pertussis ; B. bronchiseptica can persist in the environment for extended periods.

<span class="mw-page-title-main">DPT vaccine</span> Combination vaccine

The DPT vaccine or DTP vaccine is a class of combination vaccines against three infectious diseases in humans: diphtheria, pertussis, and tetanus (lockjaw). The vaccine components include diphtheria and tetanus toxoids, and either killed whole cells of the bacterium that causes pertussis or pertussis antigens. The term toxoid refers to vaccines which use an inactivated toxin produced by the pathogen which they are targeted against to generate an immune response. In this way, the toxoid vaccine generates an immune response which is targeted against the toxin which is produced by the pathogen and causes disease, rather than a vaccine which is targeted against the pathogen itself. The whole cells or antigens will be depicted as either "DTwP" or "DTaP", where the lower-case "w" indicates whole-cell inactivated pertussis and the lower-case "a" stands for "acellular". In comparison to alternative vaccine types, such as live attenuated vaccines, the DTP vaccine does not contain any live pathogen, but rather uses inactivated toxoid to generate an immune response; therefore, there is not a risk of use in populations that are immune compromised since there is not any known risk of causing the disease itself. As a result, the DTP vaccine is considered a safe vaccine to use in anyone and it generates a much more targeted immune response specific for the pathogen of interest.

<i>Bordetella</i> Genus of bacteria

Bordetella is a genus of small, Gram-negative, coccobacilli bacteria of the phylum Pseudomonadota. Bordetella species, with the exception of B. petrii, are obligate aerobes, as well as highly fastidious, or difficult to culture. All species can infect humans. The first three species to be described ; are sometimes referred to as the 'classical species'. Two of these are also motile.

<span class="mw-page-title-main">Toxoid</span> Weakened form of a toxin, often used for vaccines

A toxoid is an inactivated toxin whose toxicity has been suppressed either by chemical (formalin) or heat treatment, while other properties, typically immunogenicity, are maintained. Toxins are secreted by bacteria, whereas toxoids are altered form of toxins; toxoids are not secreted by bacteria. Thus, when used during vaccination, an immune response is mounted and immunological memory is formed against the molecular markers of the toxoid without resulting in toxin-induced illness. Such a preparation is also known as an anatoxin. There are toxoids for prevention of diphtheria, tetanus and botulism.

Adhesins are cell-surface components or appendages of bacteria that facilitate adhesion or adherence to other cells or to surfaces, usually in the host they are infecting or living in. Adhesins are a type of virulence factor.

<span class="mw-page-title-main">Pertussis toxin</span> Group of toxins

Pertussis toxin (PT) is a protein-based AB5-type exotoxin produced by the bacterium Bordetella pertussis, which causes whooping cough. PT is involved in the colonization of the respiratory tract and the establishment of infection. Research suggests PT may have a therapeutic role in treating a number of common human ailments, including hypertension, viral infection, and autoimmunity.

<i>Bordetella pertussis</i> Species of bacterium causing pertussis or whooping cough

Bordetella pertussis is a Gram-negative, aerobic, pathogenic, encapsulated coccobacillus bacterium of the genus Bordetella, and the causative agent of pertussis or whooping cough. Its virulence factors include pertussis toxin, adenylate cyclase toxin, filamentous hæmagglutinin, pertactin, fimbria, and tracheal cytotoxin.

Virulence factors are cellular structures, molecules and regulatory systems that enable microbial pathogens to achieve the following:

Adenylate cyclase toxin is a virulence factor produced by some members of the genus Bordetella. Together with the pertussis toxin it is the most important virulence factor of the causative agent of whooping cough, Bordetella pertussis. Bordetella bronchiseptica and Bordetella parapertussis, also able to cause pertussis-like symptoms, also produce adenylate cyclase toxin. It is a toxin secreted by the bacteria to influence the host immune system.

<i>Bordetella parapertussis</i> Species of bacterium

Bordetella parapertussis is a small Gram-negative bacterium of the genus Bordetella that is adapted to colonise the mammalian respiratory tract. Pertussis caused by B. parapertussis manifests with similar symptoms to B. pertussis-derived disease, but in general tends to be less severe. Immunity derived from B. pertussis does not protect against infection by B. parapertussis, however, because the O-antigen is found only on B. parapertussis. This antigen protects B. parapertussis against antibodies specific to B. pertussis, so the bacteria are free to colonize the host's lungs without being subject to attack by previous antibodies. These findings suggest B. parapertussis evolved in a host population that had already developed immunity to B. pertussis, where being able to evade B. pertussis immunity was an advantage.

The AB5 toxins are six-component protein complexes secreted by certain pathogenic bacteria known to cause human diseases such as cholera, dysentery, and hemolytic–uremic syndrome. One component is known as the A subunit, and the remaining five components are B subunits. All of these toxins share a similar structure and mechanism for entering targeted host cells. The B subunit is responsible for binding to receptors to open up a pathway for the A subunit to enter the cell. The A subunit is then able to use its catalytic machinery to take over the host cell's regular functions.

<span class="mw-page-title-main">Pertussis vaccine</span> Vaccine protecting against whooping cough

Pertussis vaccine is a vaccine that protects against whooping cough (pertussis). There are two main types: whole-cell vaccines and acellular vaccines. The whole-cell vaccine is about 78% effective while the acellular vaccine is 71–85% effective. The effectiveness of the vaccines appears to decrease by between 2 and 10% per year after vaccination with a more rapid decrease with the acellular vaccines. The vaccine is only available in combination with tetanus and diphtheria vaccines. Pertussis vaccine is estimated to have saved over 500,000 lives in 2002.

The RTX toxin superfamily is a group of cytolysins and cytotoxins produced by bacteria. There are over 1000 known members with a variety of functions. The RTX family is defined by two common features: characteristic repeats in the toxin protein sequences, and extracellular secretion by the type I secretion systems (T1SS). The name RTX refers to the glycine and aspartate-rich repeats located at the C-terminus of the toxin proteins, which facilitate export by a dedicated T1SS encoded within the rtx operon.

Adenylate cyclase toxin (CyaA) is released from bacterium Bordetella pertussis by the T1SS and released in the host’s respiratory tract in order to suppress its early innate and subsequent adaptive immune defense.

<span class="mw-page-title-main">Haemagglutination activity domain</span>

In molecular biology, the haemagglutination activity domain is a conserved protein domain found near the N terminus of a number of large, repetitive bacterial proteins, including many proteins of over 2500 amino acids. A number of the members of this family have been designated adhesins, filamentous haemagglutinins, haem/haemopexin-binding protein, etc. Members generally have a signal sequence, then an intervening region, then the region described in this entry. Following this region, proteins typically have regions rich in repeats but may show no homology between the repeats of one member and the repeats of another. This domain is suggested to be a carbohydrate-dependent haemagglutination activity site.

<span class="mw-page-title-main">Tracheal cytotoxin</span> Chemical compound

Tracheal cytotoxin (TCT) is a 921 dalton glycopeptide released by Bordetella pertussis, Vibrio fischeri, and Neisseria gonorrhoeae. It is a soluble piece of peptidoglycan (PGN) found in the cell wall of all gram-negative bacteria, but only some bacteria species release TCT due to inability to recycle this piece of anhydromuropeptide.

Vaccine resistance is the evolutionary adaptation of pathogens to infect and spread through vaccinated individuals, analogous to antimicrobial resistance. It concerns both human and animal vaccines. Although the emergence of a number of vaccine resistant pathogens has been well documented, this phenomenon is nevertheless much more rare and less of a concern than antimicrobial resistance.

Whole-cell vaccines are a type of vaccine that has been prepared in the laboratory from entire cells. Such vaccines simultaneously contain multiple antigens to activate the immune system. They induce antigen-specific T-cell responses.

References

  1. Emsley, P.; Charles, I. G.; Fairweather, N. F.; Isaacs, N. W. (1996). "Structure of Bordetella pertussis virulence factor P.69 pertactin". Nature. 381 (6577): 90–92. Bibcode:1996Natur.381...90E. doi:10.1038/381090a0. PMID   8609998.
  2. Poolman JT, Hallander HO (February 2007). "Acellular pertussis vaccines and the role of pertactin and fimbriae". Expert Rev Vaccines. 6 (1): 47–56. doi:10.1586/14760584.6.1.47. PMID   17280478.
  3. Emsley P, Charles IG, Fairweather NF, Isaacs NW (May 1996). "Structure of Bordetella pertussis virulence factor P.69 pertactin". Nature. 381 (6577): 90–2. Bibcode:1996Natur.381...90E. doi:10.1038/381090a0. PMID   8609998.
  4. 1 2 3 4 Inatsuka CS, Xu Q, Vujkovic-Cvijin I, Wong S, Stibitz S, Miller JF, Cotter PA (July 2010). "Pertactin is required for Bordetella species to resist neutrophil-mediated clearance". Infection and Immunity. 78 (7): 2901–9. doi:10.1128/IAI.00188-10. PMC   2897405 . PMID   20421378.