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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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Basics of current antimycobacterial treatment
Šilhavá, Kristýna ; Janďourek, Ondřej (advisor) ; Diepoltová, Adéla (referee)
Charles University, Faculty of Pharmacy in Hradec Kralove Department of Biological and Medical Sciences Study program: Pharmacy Author: Kristýna Šilhavá Supervisor: PharmDr, Ondřej Janďourek, Ph.D. Title of diploma thesis: Basics of current antimycobacterial therapy The aim of the theoretical part of this thesis is to summarize information regarding mycobacteria, mycobacterial infections and particularly their treatment. Infections caused by mycobacteria are widespread worldwide and a large part of the population is infected with them each year. The most common forms are pulmonary, but practically any organ of the human body can be affected. Although these diseases are treatable with combinations of antimycobacterial drugs, the number of cases with drug resistant forms of mycobacterial diseases is currently on the rise. Therefore, emphasis is placed on the development and testing of new drugs that would be able to treat these resistant forms of diseases in the future. The experimental part is dedicated to testing newly synthesized antimycobacterial compounds that were tested using the microdilution broth method against five strains of Mycobacterium genus (M. smegmatis, M. aurum, M. avium, M. kansasii and M. tuberculosis H37Ra). The results are interpreted and evaluated in terms of the...
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Mycobacterial resistance against currently used antimycobacterial drugs
Lanková, Markéta ; Janďourek, Ondřej (advisor) ; Konečná, Klára (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Study programme: Pharmacy Candidate: Markéta Lanková Supervisor: PharmDr. Ondřej Janďourek, Ph.D. Title of diploma thesis: Mycobacterial resistance against currently used antimycobacterial drugs Keywords: Mycobacteria, Mycobacterioses, Resistance, Antimycobacterials, Microdilution broth method, Minimum inhibition concentration The successful treatment of mycobacterial diseases is nowadays often confronted with the declining effect of antituberculotics and other antimicrobial agents, which are often used in the therapy of mycobacterial diseases. The goal of the theoretical part of the thesis was to focus on a comprehensive assessment of the issue of resistance to the current therapeutics used in the fight against resistant mycobacterial strains, to summarize the basic characteristics of the genus Mycobacterium, to address resistant TBC and NTM, and to describe the mechanisms of action and resistance known so far for individual therapeutics, which are often interrelated. The emergence of highly resistant mycobacterial strains is constantly increasing the risk of serious, life-threatening infections. The mechanisms of resistance either arise from the natural properties of the cell or develop gradually as a result of external stimuli, which is...
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Natural compounds active against mycobacteria (review)
Kunáková, Martina ; Krátký, Martin (advisor) ; Vinšová, Jarmila (referee)
The main topic of the bachelor thesis is compounds isolated from natural sources, which contribute significantly to the discovery of new therapeutic methods in many medical problems. The aim of the work, was to focus specifically on those compounds that showed significant antimycobacterial activity against pathogens of the genus Mycobacterium, especially against M. tuberculosis. The theoretical part focuses on the genus Mycobacterium itself and its basic characteristics. In addition, the work also focused on the specific species causing the non-tuberculous forms of the disease and those behind the outbreak of tuberculosis in the human body. The last chapter of the theoretical part deals with tuberculosis and its brief description, together with the treatment and the issues related to development of drug resistance during treatment. In the following section, specific compounds that exhibit antimycobacterial activity and have the potential to be developed as new drugs are described. Keywords: aldehydes, alkaloids, antituberculotics, compounds of natural origin, cyanobacteria, essential oils, Mycobacterium tuberculosis, mycobacteria, naphthoquinones, resistance, steroid hormones, terpenes, triterpenes, tuberculosis
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In vitro screening of potential antimycobacterial compounds against fast growing strains of Mycobacterium genus
Židková, Lenka ; Janďourek, Ondřej (advisor) ; Jílek, Petr (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Study program: Specialist in Laboratory Methods Candidate: Bc. Lenka Lyčková Supervisor: PharmDr. Ondřej Janďourek, Ph.D. Title of diploma thesis: In vitro screening of potential antimycobacterial compounds against fast growing strains of Mycobacterium genus The aim of this work is to determine the efficacy of new compounds for possible treatment of tuberculosis in the future. A microdilution broth method with already proven procedure on Mycobacterium aurum and Mycobacterium smegmatis strains was used to determine the minimum inhibitory concentration of compounds. The theoretical part summarizes the epidemiological situation of recent years with global trends in the incidence and mortality of tuberculosis in the world and in the Czech Republic, including prospective plans for remediation in the time horizon. Mycobacteria are described in the main representation with M. tuberculosis. Tuberculosis disease - its history, forms, diagnosis and treatment with antituberculotics, which are divided according to the use lines, new drugs and drugs in development. The experimental part contains qualitative and quantitative methods of testing mycobacteria and captures the microdilution broth method used in...
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Regulation of mycobacterial transcription
Kafka, Vojtěch ; Krásný, Libor (advisor) ; Dostálová, Hana (referee)
RNA polymerase (RNAP) is the enzyme that catalyzes synthesis of RNA. Mycobacterial RNAP significantly differs from RNAPs from other bacterial species. It requires special transcription factors such as RbpA or CarD. Another difference is the presence of a small RNA (sRNA), Ms1, that binds to mycobacterial RNAP. Ms1 regulates the amount of RNAP in the cell. In our laboratory we recently discovered MoaB2, a new binding partner of mycobacterial A (encoded by sigA), an RNAP subunit, which is essential for recognition of the initial promoter sequence and initiation of transcription. The function of MoaB2 in the regulation of transcription and gene expression is still unknown. The first aim of this Thesis is contribute to elucidation of the mechanism by which Ms1 affects the amount of RNAP. The experiments revealed that this regulation occurs at the level of transcription; Ms1 affects the activity of promoter(s) that drive the transcription of rpoB- rpoC that encode the two catalytic subunits of RNAP. The second aim of this Thesis is to characterize the interactions of MoaB2 with protein of the transcription apparatus. The results confirmed the interaction of MoaB2 with A and showed that neither RNAP nor transcription factors RbpA and CarD are required for this interaction. Finally, a role of the...
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Pathogenesis of infectious disease caused by bacterium Mycobacterium tuberculosis
Doležalová, Klára ; Janďourek, Ondřej (advisor) ; Kovařík, Miroslav (referee)
Charles University Faculty of Pharmacy in Hradec Kralove Department of Biological and Medical Sciences Study programme: Bioanalytical laboratory diagnostics in health care Author: Bc. Klára Doležalová Supervisor of diploma thesis: PharmDr. Ondřej Janďourek, Ph.D. Title of diploma thesis: Pathogenesis of infectious disease caused by bacterium Mycobacterium tuberculosis The theoretical part of this diploma thesis is concerned about tuberculosis where the main part of the thesis is focused on pathogenesis of this disease. Tuberculosis is recognized as highly infectious disease leading to the total exhaustion of the organism. The main causative agent of the above mentioned disease is Mycobacterium tuberculosis, which is transmitted to respiratory tract via inhalation of droplets from infected person and leads to the granuloma formation. For tuberculosis is typical a creation of granulomas, mainly with caseous necrosis. Highly important is accurate diagnosis and appropriately chosen treatment. The treatment consists of a long-term administration of antituberculotic drugs in combinations. The development of the resistance to one or more antituberculotics is adverse complication within the treatment procedure. The experimental part of this work pays attention to the testing of antimycobacterial activity...
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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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Mycobacterium smegmatis biofilm formation om glass and zirkonia beads-proteomic study
Sitařová, Barbora ; Weiser, Jaroslav (advisor) ; Zikánová, Blanka (referee)
Biofilms represent universal strategy for bacterial survival. Living in form of biofilms, bacteria acquire wide range of advantages over planktonically growing cultures. It can be assumed that nearly 99% of world bacterial population is living in form of biofilms. There are benefits and drawbacks associated with bacterial biofilms for mankind. Life in biofilms makes pathogens more effective and persistent through higher antibiotic resistance and helps them to hide before immune system of the host. Mycobacteria, which are capable of forming biofilms on variety of surfaces, differ from most of other bacteria by unique composition of their cell wall. It provides them with high resistance against physical or chemical damage. This is one of the reasons for considering Mycobacterium tuberculosis as a highly potent pathogen. The studies of mycobacterial biofilms are motivated by effort to improve or find new therapeutic methods. This work is aimed at morphological and proteomic comparative analyses of biofilms obtained from Mycobacterium smegmatis grown on surface of glass and silica/zirconium beads, on liquid medium surface or grown submerged in shaken planktonic culture. We have developed technique for preparation of "floating" biofilm sample to be observed in SEM. We have shown that the growth of...
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Ser/Thr protein kinases in mycobacteria
Borovcová, Taťána ; Doubravová, Linda (advisor) ; Konopásek, Ivo (referee)
The Mycobacterium tuberculosis genome encodes 11 Ser/Thr protein kinases. These protein kinases are structurally related to eukaryotic protein kinases. The phosphoproteome contains hundreds of proteins phosphorylated on Ser/Thr residues that influence all aspects of cell biology, which supports the critical role of phosphorylation in the regulation of physiology. Particularly important role in regulation belongs to protein kinases PknA, PknB, PknG and PknL, these protein kinases occur in all species of mycobacteria. Although only PknA and PknB are essencial for the M. tuberculosis, they regulate cell shape through the regulation of cell wall synthesis and cell division. Another important protein kinase is PknG, although not essential for growth it is necessary for virulence, because it promotes the survival of pathogen inside macrophages of the host. As a result, Ser/Thr protein kinases represent an interesting target for inhibitor development that could be used as drugs against tuberculosis.
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