Ar Mycobacterium tuberculosis pirmās rindas zāļu rezistenci saistīto mutāciju analīze un datu salīdzināšana ar fenotipiskās zāļu jutības pārbaudes rezultātiem.
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Date
2023
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Journal ISSN
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Rīgas Stradiņa universitāte
Rīga Stradiņš University
Rīga Stradiņš University
Abstract
Pētnieciskā darba “Ar Mycobacterium tuberculosis pirmās rindas zāļu rezistenci saistīto mutāciju analīze un datu salīdzināšana ar fenotipiskās zāļu jutības pārbaudes rezultātiem” mērķis ir identificēt ar zāļu rezistenci saistītās mutācijas M. tuberculosis genomā pirmās izvēles medikamentiem un salīdzināt iegūtos datus ar fenotipiskās zāļu jutības pārbaudes rezultātiem. Tuberkuloze ir visā pasaulē sastopama infekcijas slimība. Tā var tikt pilnīgi izārstēta, taču mūsdienās, pieaugot zāļu rezistencei, terapija kļūst sarežģītāka, laikietilpīgāka un mazāk efektīva. Pētījumā tika izmantota pilna genoma sekvenēšana – mūsdienīga metode, kura nākotnē var tikt izmantota rutīnas zāļu rezistentas tuberkulozes diagnostikā. Tā nodrošina M. tuberculosis pilna genoma datu iegūšanu un, izmantojot dažādus bioinformātiskos rīkus, ir iespējams noteikt mutācijas, kuras ir saistītas ar antimikobakteriālo līdzekļu rezistenci, kā arī noteikt mikobaktērijas genotipu. Tika veikta arī pilna genoma sekvenēšanas rezultātu salīdzināšana ar slimības vēsturē pieejamiem fenotipiskās zāļu jutības noteikšanas datiem. Datu apstrādei tika izmantota aprakstošā statistika, aprēķinot spoligotipu un mutāciju variantu sadalījumu analizētajos paraugos, izsakot iegūtos rezultātus skaitliski un procentuāli.
Pētījumā tika analizēti 59 M. tuberculosis izolātu DNS paraugi no Rīgas Austrumu klīniskās universitātes slimnīcas Laboratorijas dienesta stacionāra “Tuberkulozes un plaušu slimību centrs” klīniskās laboratorijas arhīva, kas tika iegūti laika posmā no 2013. līdz 2015. gadam. Salīdzinot pilna genoma sekvenēšanas datus ar fenotipiskās zāļu jutības rezultātiem, tika konstatētas atšķirības visiem četriem pirmās rindas prettuberkulozes medikamentiem.
Aim of the work “Analysis of first line drug resistance associated mutations of Mycobacterium tuberculosis and data comparison with phenotypic drug susceptibility testing results” is to identify drug resistance-related mutations in the genome of Mycobacterium tuberculosis for first-line drugs and to compare the obtained data with phenotypic drug susceptibility testing. Tuberculosis is a widespread infectious disease worldwide. It can be completely cured, but nowadays as drug resistance increases, therapy becomes more complicated, time-consuming, and less effective. In this study, whole genome sequencing, a modern method that may be used in routine drug-resistant tuberculosis diagnosis in the future, was performed. It provides whole genome data of Mycobacterium tuberculosis and using a variety of bioinformatics tools allows to detect mutations associated with antimycobacterial drug resistance, as well as to determine mycobacterium genotype. The results of the whole genome sequencing were also compared with phenotypic drug susceptibility data available in the medical history. Descriptive statistics were used to calculate the distribution of spoligotype and mutation variants in analyzed samples, expressing obtained results numerically and in percentage. In this study were analyzed DNA samples of 59 Mycobacterium tuberculosis isolates from Riga Eastern Clinical University Hospital Laboratory service stationary “Centre of Tuberculosis and Lung Diseases” clinical laboratory archive, which were obtained between 2013 and 2015. Comparison of whole genome sequencing data with phenotypic drug susceptibility results revealed differences between all four first-line antituberculosis drugs.
Aim of the work “Analysis of first line drug resistance associated mutations of Mycobacterium tuberculosis and data comparison with phenotypic drug susceptibility testing results” is to identify drug resistance-related mutations in the genome of Mycobacterium tuberculosis for first-line drugs and to compare the obtained data with phenotypic drug susceptibility testing. Tuberculosis is a widespread infectious disease worldwide. It can be completely cured, but nowadays as drug resistance increases, therapy becomes more complicated, time-consuming, and less effective. In this study, whole genome sequencing, a modern method that may be used in routine drug-resistant tuberculosis diagnosis in the future, was performed. It provides whole genome data of Mycobacterium tuberculosis and using a variety of bioinformatics tools allows to detect mutations associated with antimycobacterial drug resistance, as well as to determine mycobacterium genotype. The results of the whole genome sequencing were also compared with phenotypic drug susceptibility data available in the medical history. Descriptive statistics were used to calculate the distribution of spoligotype and mutation variants in analyzed samples, expressing obtained results numerically and in percentage. In this study were analyzed DNA samples of 59 Mycobacterium tuberculosis isolates from Riga Eastern Clinical University Hospital Laboratory service stationary “Centre of Tuberculosis and Lung Diseases” clinical laboratory archive, which were obtained between 2013 and 2015. Comparison of whole genome sequencing data with phenotypic drug susceptibility results revealed differences between all four first-line antituberculosis drugs.
Description
Farmācija
Pharmacy
Veselības aprūpe
Health Care
Pharmacy
Veselības aprūpe
Health Care
Keywords
Mycobacterium tuberculosis; zāļu rezistenta tuberkuloze; pirmās rindas prettuberkulozes medikamenti; pilna genoma sekvenēšana; fenotipiskā zāļu jutības pārbaude, Mycobacterium tuberculosis; drug resistant tuberculosis; first line antituberculosis drugs; whole genome sequencing; phenotypic drug susceptibility test