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Mechanisms underlying subversion of host immunity by Bordetella pertussis
Klímová, Nela ; Bumba, Ladislav (advisor) ; Černý, Jan (referee) ; Filipp, Dominik (referee)
Bordetella pertussis is a Gram-negative human-adapted pathogen of the respiratory tract and the causative agent of the whooping cough (pertussis) illness. The bacterium produces a number of virulence factors, of which adenylate cyclase toxin (ACT) and pertussis toxin (PT) play important roles in manipulation of host immune response and establishment of the early catarrhal stage of infection. Although the toxins exert their cytotoxic activity by elevation of intracellular cAMP levels, both are distinct from each other in terms of their structures, mechanisms of secretion and cell intoxication, as well as in their ability to modulate the adaptive immune response of the host. The aim of this thesis was to determine the structure- function relationship underlying the mechanism of the Type I secretion system (T1SS)- mediated secretion of ACT and to decipher the immunomodulatory properties of ACT and PT in the course of B. pertussis infection. Integrative structural biology approaches revealed that the RTX domain of ACT consists of a contiguous assembly of five Ca2+ -loaded β-roll blocks, whose co-secretional folding constitute an intramolecular Brownian ratchet that prevents backsliding of the translocating polypeptide in the T1SS conduit, thus accelerating the secretion of ACT from bacterial cells by a...
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Virulence factors of Bordetella pertussis
Držmíšek, Jakub ; Večerek, Branislav (advisor) ; Vopálenská, Irena (referee)
Bordetella pertusis is a Gram-negative, aerobic, non-spore-forming coccobacillus. Although it's strictly human pathogen, it's possible to infect other mammals at laboratory conditions. Transmission among hosts is mediated via respiratory tract droplets. Infection could be direct, host to host, alternatively by contaminated environment. Bordetella colonizes upper respiratory tract, wherefrom descends into lungs and causes disease known as whooping cough or pertussis leading to 195 000 deaths of 16 mil. incidences per year (according to WHO report from 2010). More than twenty years before, respectively to found pertussis toxin, that time intensively under examination, pertussis was marked as toxin-mediated disease. In the course of time, more other virulence factors were revealed, that could be divided into groups of adhesins, toxins and others. Adhesins are filamentous haemagglutinin, pertactin and fimbriae. Toxins include pertussis toxin, adenylate cyclase, tracheal cytotoxin, dermonecrotic toxin and lipopolysaccharide. Most of virulence factors are regulated by two component system Bvg. However, it is needed lots of other factors for successful infection as for example autotransporters or so called siderophores serving as iron acquisition from environment. Secretion of virulence factors is mediated by its...
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Bordetella pertussis and whooping cough: Bacterium and its virulence factors, epidemiology of disease and vaccination strategy.
Bočková, Barbora ; Holubová, Jana (advisor) ; Seydlová, Gabriela (referee)
Bordetella pertussis, a gram-negative bacterium, is a human pathogen which affects the upper respiratory tract. It is the causative agent of whooping cough or pertussis. B. pertussis produces several virulence factors consisting of toxins and adhesins. Whole cell vaccine and subsequent acellular vaccine were developed against pertussis in the past. However, a gradual increase of pertussis incidences has been reported in the last twenty years. This thesis provides basic information about B. pertussis and whooping cough. The main aim of the herein presented work is to summarize the contemporary epidemiologic situation along with determining reasons for increased pertussis cases. In addition, possible solutions for the present situation are proposed.
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Construction of a genetically detoxified Bordetella pertussis strain to develope a new generation of whole-cell vaccine
Bočková, Barbora ; Holubová, Jana (advisor) ; Seydlová, Gabriela (referee)
Bordetella pertussis is a strictly human pathogen colonizing the upper respiratory tract, causing a respiratory disease known as whooping cough or pertussis. The introduction of whole-cell vaccines and acellular vaccines, resulted in a significant reduction in the incidence of disease and reduce the fatalities associated with infection. However, epidemiological data show a significant increase in the incidence of the disease in recent decades. The increasing incidence is mainly attributed to the transition from the whole- cell vaccine to an acellular vaccine. Based on research from recent years has shown that acellular vaccines have many drawbacks, and it is therefore necessary to change the vaccination strategy. One possible solution to the situation is the development of a new generation of whole-cell vaccines with reduced reactogenicity. The new whole-cell vaccine was prepared by a genetically modified B. pertussis strain. B. pertussis was modified using allelic exchange to develop strain encoding enzymatically inactive pertussis toxin, modified lipid A and lacking dermonecrotic toxin. This combination of genetic modifications in mice led to a decrease in reactogenicity test vaccine in vivo. In case of intranasal infection whole-cell vaccine containing genetically modified strain is providing...
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Interaction of pathogenic Bordetella species with host cells
Čurnová, Ivana ; Petráčková, Denisa (advisor) ; Mašín, Jiří (referee)
Most of the members of the Gram-negative genus Bordetella cause severe infections of the respiratory tract in their hosts. B. pertussis and specific lineages of B. parapertussis infect humans and cause the disease known as whooping cough, a highly contagious respiratory disease that is currently on the rise even in highly vaccinated populations. Therefore, a more detailed understanding of the B. pertussis interactions with the host is crucial. B. pertussis produces a great variety of virulence factors, majority of which is regulated by the two- component BvgAS system. These factors assist the pathogen in the colonization of the host and evasion of the host immune system. The studies on host-pathogen interactions use both in vitro and in vivo infection models, which complement each other appropriately. Recently, it was demonstrated that B. pertussis escape killing and persists in macrophages, suggesting that B. pertussis can be considered as a facultative intracellular pathogen. This ability may allow the pathogen cells to persist within the host and potentially spread to the new host. The aim of this bachelor thesis was to summarize the knowledge on the host-pathogen interactions between B. pertussis and its host with focus on in vitro and in vivo infection models. The attention is paid especially...
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Construction of a genetically detoxified Bordetella pertussis strain to develope a new generation of whole-cell vaccine
Bočková, Barbora ; Holubová, Jana (advisor) ; Seydlová, Gabriela (referee)
Bordetella pertussis is a strictly human pathogen colonizing the upper respiratory tract, causing a respiratory disease known as whooping cough or pertussis. The introduction of whole-cell vaccines and acellular vaccines, resulted in a significant reduction in the incidence of disease and reduce the fatalities associated with infection. However, epidemiological data show a significant increase in the incidence of the disease in recent decades. The increasing incidence is mainly attributed to the transition from the whole- cell vaccine to an acellular vaccine. Based on research from recent years has shown that acellular vaccines have many drawbacks, and it is therefore necessary to change the vaccination strategy. One possible solution to the situation is the development of a new generation of whole-cell vaccines with reduced reactogenicity. The new whole-cell vaccine was prepared by a genetically modified B. pertussis strain. B. pertussis was modified using allelic exchange to develop strain encoding enzymatically inactive pertussis toxin, modified lipid A and lacking dermonecrotic toxin. This combination of genetic modifications in mice led to a decrease in reactogenicity test vaccine in vivo. In case of intranasal infection whole-cell vaccine containing genetically modified strain is providing...
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Bordetella pertussis and whooping cough: Bacterium and its virulence factors, epidemiology of disease and vaccination strategy.
Bočková, Barbora ; Holubová, Jana (advisor) ; Seydlová, Gabriela (referee)
Bordetella pertussis, a gram-negative bacterium, is a human pathogen which affects the upper respiratory tract. It is the causative agent of whooping cough or pertussis. B. pertussis produces several virulence factors consisting of toxins and adhesins. Whole cell vaccine and subsequent acellular vaccine were developed against pertussis in the past. However, a gradual increase of pertussis incidences has been reported in the last twenty years. This thesis provides basic information about B. pertussis and whooping cough. The main aim of the herein presented work is to summarize the contemporary epidemiologic situation along with determining reasons for increased pertussis cases. In addition, possible solutions for the present situation are proposed.
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Virulence factors of Bordetella pertussis
Držmíšek, Jakub ; Večerek, Branislav (advisor) ; Vopálenská, Irena (referee)
Bordetella pertusis is a Gram-negative, aerobic, non-spore-forming coccobacillus. Although it's strictly human pathogen, it's possible to infect other mammals at laboratory conditions. Transmission among hosts is mediated via respiratory tract droplets. Infection could be direct, host to host, alternatively by contaminated environment. Bordetella colonizes upper respiratory tract, wherefrom descends into lungs and causes disease known as whooping cough or pertussis leading to 195 000 deaths of 16 mil. incidences per year (according to WHO report from 2010). More than twenty years before, respectively to found pertussis toxin, that time intensively under examination, pertussis was marked as toxin-mediated disease. In the course of time, more other virulence factors were revealed, that could be divided into groups of adhesins, toxins and others. Adhesins are filamentous haemagglutinin, pertactin and fimbriae. Toxins include pertussis toxin, adenylate cyclase, tracheal cytotoxin, dermonecrotic toxin and lipopolysaccharide. Most of virulence factors are regulated by two component system Bvg. However, it is needed lots of other factors for successful infection as for example autotransporters or so called siderophores serving as iron acquisition from environment. Secretion of virulence factors is mediated by its...
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The Incidence of Pertussis in South Bohemia
HOLINKOVÁ, Petra
The thesis deals with the problem of the occurrence of whooping cough in the South Bohemian Region in the period of 2003-2012. Despite the high level of vaccination the incidence of this illness after a significant fall in the 1980s has been growing constantly since 1993. This trend evidently also applies in other developed countries with a high rate of vaccination. The main aim is to draw up an overview of the occurrence of whooping cough in the South Bohemian Region in the monitored period of the last 10 years, compare this occurrence with other regions in the Czech Republic and map out the changes which have occurred in whooping cough vaccination. Quantitative and qualitative research was chosen to process the empirical part. Data for quantitative research was acquired from the database of infectious diseases (EPIDAT), and consisted of reported cases of whooping cough. Another essential group of data were demographic figures about the number and age structure of the population. The second qualitative part was drawn up on the basis of a literary search. I acquired additional information by communicating with individual territorial workplaces of the Regional Hygiene Station of the South Bohemian Region based in České Budějovice. Using the processed data I discovered that the incidence of whooping cough in the South Bohemian Region does not have an ascending trend in 2003-2012 unlike the trend in the whole of the Czech Republic. The highest occurrence of whooping cough in the Czech Republic in the monitored period was reported in the 10-14 age group. The research also showed that in the period of 2003-2012 individual regions differed greatly in the occurrence and can be divided into two groups ? regions with the highest reached incidence below 10 cases/100,000 people and regions with incidence with the highest reached incidence above 10 cases/100,000 people which includes the South Bohemian Region. There have been many changes in the vaccination of whooping cough and the most important was the transition from whole cell vaccine to acellular in 2007 and adding a 6th booster dose between the 10th and 11th year in 2009. The greatest attention should be paid above all to increase information or test the knowledge of the lay public, especially women preparing for pregnancy and people taking care of newborn babies and infants about the occurrence, potential risks and possibilities of vaccination against this infection even at an adult age. In my opinion a further necessity is the consolidation of diagnostics, definition of a case and procedures of surveillance throughout the Czech Republic, education of paediatricians and general practitioners about the illness and topicality of the problem, an appeal to report the occurrence of this infection to epidemiologists, observing the isolation of the patient, monitoring possible epidemiological connections between cases and making use of the offer of the NRL (National Reference Laboratory) services against whooping cough and diphtheria. This thesis can be used in practice as a summary of information material for the lay and professional public about the occurrence of whooping cough in the South Bohemian Region and throughout the Czech Republic and overview of vaccination against whooping cough. It can be an incentive for further anti-epidemic measures and the need for further research into this problem.
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Contemporary problems of Bordetella pertussis and Bordetella parapertussis
ŠIMÁNKOVÁ, Petra
Current Issues Linked to Bordetella pertussis and Bordetella parapertussis Abstract Bordetella pertussis and Bordetella parapertussis are causative agents of infections affecting airways. These agents are Gram-negative, aerobic coccobacillus of the genus Bordetella and the family Brucellaceae. Subjects infected with bacteria Bordetella pertussis develops into a highly contagious infection called whooping cough. Those infected with Bordetella parapertussis show milder clinical symptoms than those infected with Bordetella pertussis. The highly contagious infection affects the airways and is considered to be one of the most serious infections found in children. Before proper vaccine was discovered, this infection caused high mortality especially among one-year-old babies and younger. The most vulnerable group of subjects comprises of infants. Infection is even observed in subjects of 10+ years of age and may infect even the adults that are identified as the source of infection who subsequently infect their children. In case a subject is suspected of being infected with the genus Bordetella pertussis or Bordetella parapertussis, it is important to test a proper biological sample, i.e. epipharynx swab. Objective of the thesis: The objective of the thesis is to acquire practical skills in laboratory work. This concerns bacterial culture tests of epipharynx swabs taken from subjects suspected of being infected with bacteria Bordetella parapertussis and Bordetella pertussis on one hand, and assessment of sensitivity to antibiotics in case of isolated genera Bordetella parapertussis and Bordetella pertussis on the other. Also, it is meant to identify to what extent the two bacteria differ from each other. Another objective was to find out and assess the data collected in the region of Jindřichův Hradec and gathered from samples tested by Laboma s.r.o. microbiological laboratory that concerned the occurrence of the bacteria Bordetella parapertussis and Bordetella pertussis in each of the past 3 years. The data gathered in relation to the occurrence of the bacterium were processed statistically. Subsequently, medical procedures carried out in case of suspicion of airways infection caused by the bacteria Bordetella pertussis were scrutinized. The information was collected by questionnaires. Hypotheses: Hypothesis 1: Culture diagnosis of Bordetella parapertussis will be less time demanding than diagnosis of Bordetella pertussis. Hypothesis 2: The occurrence of Bordetella pertussis and Bordetella parapertussis is higher in autumn and spring periods. Hypothesis 3: The occurrence of Bordetella pertussis and Bordetella parapertussis is most frequent among the children of 10-14 years of age. Conclusion: The outcomes of this bachelor?s thesis show that cultures of Bordetella pertussis and Bordetella parapertussis are demanding bacteria in terms of growth. Bordetella parapertussis differs from Bordetella pertussis not only in terms of the course of bacterias cultures, but also in terms of appearance, biochemical properties, and sensitivity to antibiotics. Hypotheses 1, 2, and 3 were confirmed following the outcomes of the performed research.
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