Bordetella parapertussis
Classification
Domain: Bacteria
Phylum: Proteobacteria
Class: Betaproteobacteria
Order: Burkholderiales
Family: Alcaligenaceae
Genus and Species: Bordetella parapertussis [1]
Species
Bordetella parapertussis
Description and Significance
Describe the appearance, habitat, etc. of the organism, and why you think it is important.
‘’Bordetella parapertussis’’ is a Gram-negative β-proteobacteria coccobacillus, Additionally, It is an obligate aerobe, thriving in environments rich in oxygen. [6] This bacterium primarily inhabits the human respiratory mucosa, where it establishes infection and spreads through person-to-person transmission. It can also infect sheep, causing respiratory illness in these animals. B. parapertussis strains isolated from humans, B. parapertussis (hu), and those from sheep, B. parapertussis (ov), are genetically distinct, suggesting independent evolution from a common ancestor, B. bronchiseptica. [6]
B. parapertussis is a significant pathogen, causing upper respiratory tract infections characterized by pertussis, or whooping cough. Although typically producing a milder form of whooping cough compared to Bordetella pertussis, it can still lead to severe symptoms, especially in infants under six months of age. The bacterium contributes to outbreaks of whooping cough, accounting for 5-30% of cases, particularly in regions with acellular pertussis immunization programs. [12] Notably, the increase in ‘’B. parapertussis’’ cases may be attributed to its fitness under the pressure of acellular pertussis vaccines, as it does not express pertussis toxin (Ptx), a major virulence factor targeted by these vaccines. [9] Understanding ‘’B. parapertussis’’ is crucial for disease management and vaccination strategies, given its role in respiratory infections and its potential to evade existing vaccines, highlighting the importance of ongoing research and surveillance efforts.
Genome Structure
Describe the size and content of the genome. How many chromosomes? Circular or linear? Other interesting features? What is known about its sequence?
Bordetella parapertussis typically possesses a single circular chromosome, with a genome size of approximately 4.7 million base pairs (Mbp) and a G+C content of 65%. Comparative genomic analysis has identified 81 single nucleotide polymorphisms and 13 short insertions and deletions compared to the reference genome Bordetella parapertussis 12822, indicating ongoing evolutionary changes.
This bacterium has diverged into two distinct lineages: one causing whooping cough in infants and the other infecting sheep. It shares a common ancestor with B. pertussis, both having evolved independently from B. bronchiseptica ancestors.
Unlike B. pertussis, B. parapertussis is oxidase-negative, suggesting differences in respiratory mechanisms. It can utilize other oxidases in electron transport due to the absence of cytochrome c oxidase.
A specific genome sequence, IRBP134, isolated from a fully vaccinated infant in Iran, was sequenced using Nextseq technology. The assembly generated 72 scaffolds with a genome size of 4,720,964 base pairs, including 4,620 potential coding sequences and 55 RNA sequences. The presence of 63 tRNAs and one large and one small subunit of ribosomal RNA was also identified in the genome annotation. [9]
Cell Structure, Metabolism and Life Cycle
Interesting features of cell structure; how it gains energy; what important molecules it produces.
Ecology and Pathogenesis
Habitat; symbiosis; biogeochemical significance; contributions to environment.
If relevant, how does this organism cause disease? Human, animal, plant hosts? Virulence factors, as well as patient symptoms.
Bordetella parapertussis is transmitted through respiratory droplets and cannot survive in the outside environment. Upon entering the host, B. parapertussis encounters its optimal growth temperature (37°C), which activates the BvgA/S pathway. The BvgA/S pathway initiates the transcription of virulence-activating genes, which signals host colonization of the ciliated respiratory epithelial cells. B. parapertussis possesses many virulence factors that maintain its inhabitance in the upper respiratory tract and sustains growth and reproduction.
One of the most notable virulence factors is Filamentous Hemagglutinin (FHA). FHA is a long, rod-shaped protein that is both a surface antigen and a secreted protein. As a surface antigen, it binds to ciliated respiratory epithelial cells and allows tracheal colonization. FHA promotes Interleukin 10, a cytokine with anti-inflammatory properties, [18] and reduces Interleukin 12, which promotes both the innate and adaptive immune response. [19] When FHA is secreted it binds to monocytes where it inhibits antigen-dependent CD4+ T cell proliferation and generates apoptosis. [16] CD4+ T cells rely on antigen presenting monocytes to activate. CD4+ T cells are responsible for producing cytokines, which help activate the specific immune response, and recruit Macrophages, cytotoxic T cells, and B cells. Suppression of the specific immune response limits destruction of the pathogen by macrophages and cytotoxic T cells and the production of neutralizing antibodies by B cells. [17]
Another important virulence factor is Pertactin (PRN). It is an autotransporter responsible for adhesion to the ciliated respiratory cells. PRN is comprised of 16 right-handed parallel β-helixes. It is the largest β-helix structure ever recorded. The ACV vaccine targets PRN for phagocytosis through a cascade of immunological responses mediated by C1q. When antibodies bind to the PRN antigen, they arrange on the bacterial surface in a conformation favorable for C1q binding. C1q binding activates a cascade of synergistic activities: the formation of a Membrane Attack Complex (MAC) which forms pores in the bacterial surface leading to osmolysis, the depositing of C3b factors which act as opsonins (or tags for immune system recognition), and the binding of FcR (fragment crystallizable region) to PRNs to activate phagocytosis. PRN is an important target for the ACV vaccine. However, PRN-negative B. parapertussis is becoming increasing common worldwide, likely due to the selective pressures of the ACV vaccine. PRN-negative B. parapertussis were shown to have either one or both nonsense mutations: either a deletion of an adenine in region I or a guanine deletion in region II of the PRN gene.
The secreted neurotoxin, Dermonecrotic Toxin (DNT), causes encephalopathy, which is a fatal complication that effects 1% of patients. DNT targets T-type voltage-gated calcium channel, CaV3, on the central nervous system. Mice injected with DNT showed bleeding of the cerebellum and around the olfactory bulb. [22] The mice injected with DNT showed increased myelin basic protein, a myelination protein, and interleukin-6 protein, a protein produced in response to infections, [23] in the cerebrospinal fluid, indicating inflammation and demyelination in the central nervous system. [22]
Tracheal Cytotoxin:
The tracheal cytotoxin is a cell wall peptidoglycan fragment that kills ciliated respiratory epithelial cells through the production of nitric oxide. It also mediates the production of interleukin 1, a pyrogen. [24]
Adenylate Cyclase Toxin (CyaA):
CyaA is a secreted antigen that is released during early respirator colonization and binds to neutrophils and macrophages. Once it invades the host's immune cells, it is activated by calmodulin and causes a massive increase in cAMP production. CyaA removes two phosphates from ATP to produce cAMP. Because cAMP is a signal for many processes in the cell, its overproduction disrupts many cellular functions. CyaA intoxication leads to apoptosis, weakening the host’s immune response and supporting bacterial colonization. [21]
References
[1] [Schoch CL, et al. NCBI Taxonomy: a comprehensive update on curation, resources and tools. Database (Oxford). 2020: baaa062. PubMed: 32761142 PMC: PMC7408187]
[6] Parkhill, J., Sebaihia, M., Preston, A. et al. Comparative analysis of the genome sequences of Bordetella pertussis, Bordetella parapertussis and Bordetella bronchiseptica. Nat Genet 35, 32–40 (2003). https://doi-org.proxyiub.uits.iu.edu/10.1038/ng1227
[9] Safarchi, A., Saedi, S., Tay, C. Y., Lamichhane, B., Nakhost Lotfi, M., & Shahcheraghi, F. (2022). Genome Characteristic of Bordetella parapertussis Isolated from Iran. Current microbiology, 79(10), 314. https://doi.org/10.1007/s00284-022-03009-x
[12] Brinig, M. M., Register, K. B., Ackermann, M. R., & Relman, D. A. (2006). Genomic features of Bordetella parapertussis clades with distinct host species specificity. Genome biology, 7(9), R81. https://doi.org/10.1186/gb-2006-7-9-r81
Author
Page authored by Sachin Gupta and Erin Goertzen, students of Prof. Jay Lennon at Indiana University.
