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Mycobacterium tuberculosis - structure and functions of the cell wall
Kukrálová, Simona ; Janďourek, Ondřej (advisor) ; Jílek, Petr (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Study program: Bioanalytical laboratory diagnostics in healthcare Candidate: Bc. Simona Kukrálová Supervisor: PharmDr. Ondřej Janďourek, Ph.D. Title of diploma thesis: Mycobacterium tuberculosis - structure and functions of the cell wall Mycobacterium tuberculosis is an intracellular pathogen that causes a disease called tuberculosis, which, along with other selected diseases, is still one of the leading causes of mortality in the world. It is estimated that more than a million people succumb to the disease each year. The remarkable structure of the cell wall of mycobacteria has a great influence on the treatment of tuberculosis itself, together with the ever-increasing incidence of multidrug- resistant and extensively resistant strains, especially in Mycobacterium tuberculosis. The research of mycobacteria is given great attention. Efforts to find new substances with antimycobacterial effect acting on individual components of the cell wall, preferably on the cell wall as a complex, are actual and are part of national as well as international programs. Theoretical part of this diploma thesis deals with current knowledge about mycobacteria with emphasis on cell wall, epidemiology of tuberculosis...
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Introduction of an invertebrate animal model, Galleria Galleria mellonellamellonella, to study the in vivo efficacy of existing and newly synthesized, candidate antituberculotics
Kubíček, Jiří ; Konečná, Klára (advisor) ; Němečková, Ivana (referee)
Charles university, Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Study program: Pharmacy Author: Jiří Kubíček Supervisor: RNDr. Klára Konečná, Ph.D. Title of thesis: Introduction of an invertebrate animal model, Galleria mellonella, to study the in vivo efficacy of existing and newly synthesized, candidate antituberculotics. Background: The aim of this diploma thesis has been to present an invertebrate organism, Galleria mellonella (G. mellonella), Pyralidae, as an alternative, more economically advantegous and morally more acceptable model for in vivo studies of an antituberculotics (anti-TB) efficacy. In the experimental part of this work, attention was paid to the optimization of methodological steps, that should lead to a higher reproducibility and validity of the obtained data. The effect of the disaggregating supplement, tyloxapol, on the growth of Mycobacterium aurum (M. aurum) was evaluated. The growth of this microbial strain in the culture medium, Middlebrook 7H9, was also mapped to determine the exponential growth phase. In the second part of the experiments, G. mellonella larvae were infected with a M. aurum bacterial strain, followed by an administration of the selected, commercially available anti-TB. Methods: To map the exponential phase of M....
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Synthesis of aerothionin analogs as potential antimycobacterial agents
Šimovičová, Martina ; Zitko, Jan (advisor) ; Zimčík, Petr (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Author: Martina Šimovičová Supervisors: Assoc. Prof. PharmDr. Jan Zitko, Ph.D.; Adjunct Prof. Paula Kiuru, Ph.D. Title of diploma thesis: Synthesis of aerothionin analogs as potential antimycobacterial agents Key words: antimycobacterial; tuberculosis; synthesis; aerothionin; bromotyrosines Drugs currently used for the treatment of tuberculosis are the result of studies carried out 50 or 60 years ago. With the constantly growing bacterial resistance to these pharmaceuticals grows also the importance of research for new antimycobacterially active compounds. The marine environment undoubtedly holds an enormous potential for discovering new leads for the development of antitubercular agents. One of these leads is a spirocyclic compound called aerothionin (1), which was found to be active against multidrug-resistant strains of Mycobacterium tuberculosis, as well as three non-tuberculosis mycobacteria (Figure 1). In addition, several spirocyclic structures (not only from marine origin) were discovered to affect on the M. tuberculosis in recent years, making this structure segment attractive for antitubercular research. Figure 1: Aerothionin (1) and general structure of the...
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Construction and characterization of recombinant adenylate cyclase toxoid of bacterium Bordetella pertussis carrying mycobacterial antigen TB7.7
Mikulecký, Pavel ; Staněk, Ondřej (advisor) ; Vopálenský, Václav (referee)
Bacterium Mycobacterium tuberculosis is an etiological agent of a deadly disease called tuberculosis that presents a global problem. According to The World Health Organization there are more than 2 billions people infected with latent tuberculosis all over the world. There is still need of specific, sensitive, quick and economic available method for identification of infected individuals. Currently in vitro blood tests are considered to be the best way of diagnosis. They are based on restimulation of specific T lymphocytes by mycobacterial antigens derived from virulent strains. There are several different approaches for enhancing of direct antigen delivery into antigen presenting cells and promising one is a genetically detoxified adenylate cyclase toxin (CyaA) of bacteria Bordetella pertussis. The main aim of the thesis includes construction and subsequent characterization of biological properties of CyaA protein carrying specific mycobacterial antigen TB7.7 in translocating domain. Here is shown that fusion protein CyaA-TB7.7 can form cation selective pores in target cell membranes and is able to deliver antigens into the cytosol of APC to be presented on surface with molecules MHC class II. Genetically detoxified CyaA- TB7.7 protein will be used to supplement current approaches such as also in vitro...
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Synthesis of aerothionin analogs as potential antimycobacterial agents
Šimovičová, Martina ; Zitko, Jan (advisor) ; Zimčík, Petr (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Author: Martina Šimovičová Supervisors: Assoc. Prof. PharmDr. Jan Zitko, Ph.D.; Adjunct Prof. Paula Kiuru, Ph.D. Title of diploma thesis: Synthesis of aerothionin analogs as potential antimycobacterial agents Key words: antimycobacterial; tuberculosis; synthesis; aerothionin; bromotyrosines Drugs currently used for the treatment of tuberculosis are the result of studies carried out 50 or 60 years ago. With the constantly growing bacterial resistance to these pharmaceuticals grows also the importance of research for new antimycobacterially active compounds. The marine environment undoubtedly holds an enormous potential for discovering new leads for the development of antitubercular agents. One of these leads is a spirocyclic compound called aerothionin (1), which was found to be active against multidrug-resistant strains of Mycobacterium tuberculosis, as well as three non-tuberculosis mycobacteria (Figure 1). In addition, several spirocyclic structures (not only from marine origin) were discovered to affect on the M. tuberculosis in recent years, making this structure segment attractive for antitubercular research. Figure 1: Aerothionin (1) and general structure of the...
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Mycobacterium tuberculosis as causative agent of grave illness
Hampl, Tomáš ; Janďourek, Ondřej (advisor) ; Voxová, Barbora (referee)
Charles University, Faculty of Pharmacy, Hradec Králové Field of study: Specialist in laboratory methods Author: Bc. Tomáš Hampl Supervisor: PharmDr. Ondřej Janďourek, Ph.D. Title of diploma thesis: Mycobacterium tuberculosis as causative agent of grave illness The aim of this diploma thesis is to deal with tuberculosis, describe the pathogen, taxonomic classification, describe the origin, course and clinical manifestations of the disease, diagnosis, including laboratory diagnostics, epidemiology of tuberculosis, treatment and prevention. Tuberculosis (TBC) is one of the deadliest infectious diseases in the world caused by bacterium M. tuberculosis in humans. TBC is sometimes referred as a disease of the past, but the recent rise in cases of the disease, and especially the spread of forms of drug-resistant TBC, makes the disease very dangerous. Currently, a major problem is the alarming rise in resistant and multi-resistant tuberculosis, which is not counteracted by commonly used first-line drugs. Therefore, there is a constant emphasis around the world on discovering and testing new potential antituberculotics that could help patients with resistant and multidrug-resistant TBC. In the experimental part, the thesis deals with screening of antimycobacterial activity of potential antituberculotics...
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In vitro screening of potential antimycobacterial compounds against fast growing strains of Mycobacterium genus II
Pchálková, Tereza ; Janďourek, Ondřej (advisor) ; Jílek, Petr (referee)
Charles University Faculty of Pharmacy in Hradec Kralove Department of Biological and Medical Sciences Study program: Specialist on Laboratory Methods Author: Bc. Tereza Pchálková Supervisor: PharmDr. Ondřej Janďourek, Ph.D. Title of diploma thesis: In vitro screening of potential antimycobacterial compounds active against fast growing strains of Mycobacterium genus II Key words: Mycobacteria, Tuberculosis, Antituberculotics, Microdilution broth method, Minimum inhibition concentration Background: The aim of this diploma thesis has been screening of in vitro antimycobacterial activity of novel compounds against fast growing strains of the genus Mycobacterium (Mycobacterium smegmatis and Mycobacterium aurum). Another aim has been predicting the structure-activity relationships for tested compounds. Methods: The technique used for activity determination was microdilution broth method. The value of minimum inhibition concentration for each compound was determined. The evaluation was performed visually and spectrophotometrically using the Alamar blue indicator. Results: A total of 79 compounds were tested. 22 tested compounds showed significant activity against mycobacteria. The substances were sorted according to the similarity in chemical structure into 10 groups. From a chemical point of view, these...
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The current epidemiological situation of tuberculosis in Central Bohemian Region
Jedličková, Kateřina ; Lustigová, Michala (advisor) ; Jágrová, Zdeňka (referee)
Tuberculosis (TBC) is an infectious disease with long history, that goes to the beginnings of humanity. Nowadays, TBC is mainly creating socioeconomic issues connected with overpopulation. In 21st century, TBC remains major concern for public health in terms of infectious diseases in European region. Even though the joint efforts of political, economical and health institution are being successful, there is still need for better health care coordination, diagnosis improvement, and help to the endangered groups of people in lower income countries. The aim of this thesis is to assess the epidemiological situation of TBC incidence in the Central Bohemia region in the years from 2008 to 2017 with a special focus on impact of health and socioeconomic risk factor for developing TBC. Research questions concern population structure characteristics of TBC patients, differences between sexes and factors that affect TBC death. Methods of contingence tables, χ2 -test of independence and logistic regression were applied to analyse of the effect of age, comorbidities, and risk behaviour on the development of TBC. It was found that there are differences in age structure of patients with TBC between men and women. The most affected by TBC are men in middle and older age, while women are affected in the oldest age...
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In vitro screening of potential antimycobacterial compounds against fast growing strains of Mycobacterium genus II
Pchálková, Tereza ; Janďourek, Ondřej (advisor) ; Jílek, Petr (referee)
Charles University Faculty of Pharmacy in Hradec Kralove Department of Biological and Medical Sciences Study program: Specialist on Laboratory Methods Author: Bc. Tereza Pchálková Supervisor: PharmDr. Ondřej Janďourek, Ph.D. Title of diploma thesis: In vitro screening of potential antimycobacterial compounds active against fast growing strains of Mycobacterium genus II Key words: Mycobacteria, Tuberculosis, Antituberculotics, Microdilution broth method, Minimum inhibition concentration Background: The aim of this diploma thesis has been screening of in vitro antimycobacterial activity of novel compounds against fast growing strains of the genus Mycobacterium (Mycobacterium smegmatis and Mycobacterium aurum). Another aim has been predicting the structure-activity relationships for tested compounds. Methods: The technique used for activity determination was microdilution broth method. The value of minimum inhibition concentration for each compound was determined. The evaluation was performed visually and spectrophotometrically using the Alamar blue indicator. Results: A total of 79 compounds were tested. 22 tested compounds showed significant activity against mycobacteria. The substances were sorted according to the similarity in chemical structure into 10 groups. From a chemical point of view, these...
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Nutricional care for patients with TBC
Vlášková, Lenka ; Zlatohlávek, Lukáš (advisor) ; Svačina, Štěpán (referee)
The thesis deals with the nutritional care for patients with TBC. The theoretical part describes the history of the disease, its etiology, pathogenesis, treatment and epidemiology. The tuberculosis current care of patients in the Czech Republic, the incidence of tuberculosis in our country and in the world and the specifics of nutricional care for patients with tuberculosis. In the practical part i deal with nutritional care in five case reports and interpret the records from the patient's medical records. I suggest to each patient an optimal diet based on the calculated nutritional need. Keywords: tuberculosis, nutritional care, disease, nutrition, diet
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