Бордетелла пертуссис: Құрамы, қасиеттері және ауру тудыру механизмі

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. The bacteria are spread by airborne droplets and the disease's incubation period is 7–10 days on average (range 6–20 days). Humans are the only known reservoir for B. pertussis. The complete B. pertussis genome of 4,086,186 base pairs was published in 2003. Compared to its closest relative B. bronchiseptica, the genome size is greatly reduced. This is mainly due to the adaptation to one host species (human) and the loss of capability of survival outside a host body. Like B. bronchiseptica, B. pertussis can express a flagellum like structure, even though it has been historically categorized as a nonmotile bacterium.

The genus Bordetella contains nine species: B. pertussis, B. parapertussis, B. bronchiseptica, B. avium, B. hinzii, B. holmesii, B. trematum, B. ansorpii, and B. petrii. 16S rRNA is a component of all bacteria that allows for the comparison of phyla within a sample. The expansion of human development into the agricultural field caused there to be an influx of human to soil contact. This increase not only created more advantageous environments for the ancestors of Bordetella not only to thrive in, but to spread to humans as well. Over time, Bordetella, like B. pertussis, has adapted to specifically infect humans and they are still able to multiply and thrive in soil conditions. It was initially determined that B. pertussis is a monomorphic pathogen in which majority of strains found had the same two types of alleles: ptxA1 or ptxA2. Modern developments in genome sequencing have allowed B. pertussis to be studied more allowing for the discovery of the ptxP region. Through studying the gene, there has been evidence of mutations within the gene that show missing genomes present on the DNA strand. A study by Bart et al., revealed that 25% of the genes on the Tohama I reference strain of B. pertussis sequence were missing in comparison to the ancestral strains. These mutations were noted to be caused by an increase in intragenomic recombination with loss of DNA. Genes controlled by the BvgAS system have transformed B. pertussis into a much more contagious pathogen. optimal to thrive in the human body. The max pH level for their growth was at a pH level of 8.0. The minimum pH range for minimal growth was at pH 6.0 6.5. The bacteria are not able to reproduce at pH levels lower than 5.0. In addition, Bordetella pertussis favors a temperature range of 35 °C to 37 °C. It is a strict aerobe as mentioned previously and its nutritional requirements are meticulous in its requirement for nicotinamide supplement. It has been identified that growth of the bacteria is hindered in the presence of fatty acids, peroxide media, metal ions, and sulfides. As a strict aerobe, the bacteria requires oxygen to grow and sustain. Such aerobes undergo cellular respiration to metabolize substances using oxygen. In such respiration, the terminal electron acceptor for the electron transport chain is oxygen. The organism is oxidase positive, but urease, nitrate reductase, and citrate negative.

B. pertussis presents unique challenges and opportunities for metabolic modeling, especially given its reemergence as a pathogen. Elevated glutamate levels were found to slow growth due to oxidative stress, revealing a complex relationship. This effect is compounded by observations suggesting that a small starting population could amplify oxidative stress through quorum sensing, a phenomenon deserving further investigation. When B. pertussis is in a balanced that medium of lactate and glutamate that does not accumulate ammonium, a partially faulty citric acid cycle in B. pertussis and its ability to synthesize and break down β hydroxybutyrate is observed. Cultivating B. pertussis in this medium resulted in some production of polyhydroxybutyrate but no excretion of β hydroxybutyrate, indicating a more efficient conversion of carbon into biomass compared to existing media formulations. In biofilm conditions, B. pertussis cells exhibited increased toxin levels alongside reduced expression of certain proteins, indicating a metabolic shift towards utilizing the full tricarboxylic acid (TCA) cycle over the glyoxylate shunt. These changes correlated with heightened polyhydroxybutyrate accumulation and superoxide dismutase activity, potentially contributing to prolonged survival in biofilms. Despite a less negative energy profile compared to host tissues like the human respiratory system, B. pertussis efficiently couples biosynthesis with catabolism, sustaining robust growth even after extended incubation periods. Outbreaks of whooping cough have been observed among chimpanzees in a zoo, and among wild gorillas; in both cases it is considered likely that the infection was acquired as a result of close contact with humans. Several zoos have a long standing custom of vaccinating their primates against whooping cough. Research shows that some primate species are highly sensitive to B. pertussis, and developed a clinical whooping cough in high incidence when exposed to low inoculation doses. Whether the bacteria spread naturally in wild animal populations has not been confirmed satisfactorily by laboratory diagnosis. In research settings, baboons have been used as a model of the infection although it is not known whether the pathology in baboons is the same as in humans.

Pertussis is an infection of the respiratory system characterized by a “whooping” sound when the person breathes in. B. pertussis infects its host by colonizing lung epithelial cells. The bacterium contains a surface protein, filamentous haemagglutinin adhesin, which binds to the sulfatides found on cilia of epithelial cells. Other adhesins are fimbriae and petractin. Once anchored, the bacterium produces tracheal cytotoxin, which stops the cilia from beating. This prevents the cilia from clearing debris from the lungs, so the body responds by sending the host into a coughing fit. B. pertussis has the ability to inhibit the function of the host's immune system. The toxin, known as pertussis toxin, inhibits G protein coupling that regulates an adenylate cyclase mediated conversion of ATP to cyclic adenosine monophosphate. The result is that phagocytes convert too much adenosine triphosphate to cyclic adenosine monophosphate, causing disturbances in cellular signaling mechanisms, and preventing phagocytes from correctly responding to the infection. Pertussis toxin, formerly known as lymphocytosis promoting factor, causes a decrease in the entry of lymphocytes into lymph nodes, which can lead to a condition known as lymphocytosis, with a complete lymphocyte count of over 4000/μl in adults or over 8000/μl in children. Beside targeting lymphocytes, it limits neutrophil migration to the lungs. It also decreases the function of tissue resident macrophages, which are responsible for some bacterial clearance. The infection of B. pertussis occurs mostly in children under the age of one since this is when they are unimmunized, or children with faded immunity, normally around the ages 11 through 18. The signs and symptoms are similar to a common cold: runny nose, sneezing, mild cough, and low grade fever. The patient becomes most contagious during the catarrhal stage of infection, normally two weeks after the coughing begins. It may become airborne when the person coughs, sneezes, or laughs. The paroxysmal cough precedes a crowing inspiratory sound characteristic of pertussis. After a spell, the patient might make a “whooping” sound when breathing in, or may vomit. Transmission rates are expected to rise as the host experiences their most contagious stage when the total viable count of B. pertussis is at its highest. After the host coughs, the bacteria in their respiratory airways will be exposed into the air by way of aerosolized droplets, threatening nearby humans. A human host can exhibit a range of physical reactions as a result of the  B. pertussis pathogen, depending on how well their body is equipped to fight infection. However, for B. pertussis to persist in a population the bacterium needs an uninterrupted chain of transmission as there are no animal reservoirs and the bacteria do not survive in the environment. B. pertussis primarily spreads through respiratory droplets, requiring direct contact between individuals due to its short survival time outside the body. It was noted that between 1991 and 2008, there were 258 deaths for infants 8 months old and younger.

Whooping cough is treated by macrolides, for example erythromycin. The therapy is most effective when started during the incubation period or the catarrhal period. It is ideal for treatment should be within 1–2 weeks from onset of symptoms. When applied during the paroxysmal cough phase, the time of reconvalescence is not affected, only further transmission is reduced to 5–10 days after infection.

Pertussis vaccine has been widely used since the second half of the 20th century. These acellular vaccines are also intramuscular and are composed of purified surface antigens, mainly fimbriae, filamentous hemagglutinin, pertactin and pertussis toxin. Both vaccines are still used today, with the aP vaccine predominantly used in developed countries. The aP vaccine is also a part of the diphtheria, tetanus, and acellular pertussis (DTaP) immunization. Cases in infants are common and often have serious impacts as they are more susceptible to Bordetella pertussis than adolescents and healthy adults. Therefore, to decrease likelihood of contracting and spreading this disease, parents are recommended to receive the preventative vaccine. 'With the resurgence of pertussis cases, there are concerns regarding the level of protection provided by the current vaccine. This vaccine does not offer protection against other species of Bordetella such as B. holmesii and B. bronchiseptica and further highlights the need for a revamped vaccine. Research is currently developing a novel vaccine such as the BPZE1, which is a live attenuated vaccine against B. pertussis and challenges the other pathogens in the 'Classical Bordetellae.'' This new vaccine inactivates the gene encoding 3 major toxins with only a single intranasal dose. It is currently being studied for safety in immunocompromised patients and pregnant women. There are other promising vaccines that are under study and in trial periods for accuracy, efficacy, and safety.