Computational Drug Resistomes Analyses of Mycobacteroides Abscessus Complex


Chong, Shay Lee (2021) Computational Drug Resistomes Analyses of Mycobacteroides Abscessus Complex. Masters thesis, Multimedia University.

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Mycobacteroides abscessus complex (MABC) is an emerging pathogen that causes human infections and resistance to multiple antibiotics. In this study, the genome data of 1,581 MABC strains were downloaded from NCBI Genome database for resistome analysis. The MABC strains were classified based on phylogenomic analysis and examined to identify the differences in antibiotic resistance proteins (ARPs) distribution among MABC subspecies. In addition, evolutionary analysis was performed on resistomes to evaluate the impact of evolution on the resistance of MABC. Multiple Biopython and Bash scripts were coded to handle and manage the genomes big data. A total of 395 putative ARPs, distributed among 28 antibiotic classes in accordance with CARD and ARG-ANNOT were predicted. The ARPs most frequently identified in MABC were those associated with resistance to multiple antibiotic classes, beta-lactams, and aminoglycosides. After excluding ARPs that had undergone recombination, two ARPs were predicted to be influenced by diversifying selection and 202 experienced purifying selection. The wide occurrence of purifying selection suggested that the amino acid diversity of commonly shared ARPs in MABC may have been reduced to achieve protein stability. The unequal distribution of ARPs in members of the MABC complex could be due to horizontal gene transfer or ARPs pseudogenization events. Most (81.5%) of the ARPs were observed in the accessory genome and 72.2% ARPs were highly homologous to proteins associated with mobile genetic elements such as plasmids, prophages, and viruses. On the other hand, with TBLASTN search, only 18 of the ARPs were identified as pseudogenes. Altogether, this study suggested an important role of horizontal gene transfer in shaping the resistome of MABC. The present study provides insights into the antibiotic resistomes in MABC and the evolutionary forces exerted on the resistomes. These findings would be useful in designing new therapeutic strategies and potential discovery of new antibiotics.

Item Type: Thesis (Masters)
Additional Information: Call No: QH447 .C46 2021
Uncontrolled Keywords: Genomics. Genome research.
Subjects: Q Science > QH Natural history
Divisions: Faculty of Information Science and Technology (FIST)
Depositing User: Ms Nurul Iqtiani Ahmad
Date Deposited: 24 Feb 2023 09:17
Last Modified: 24 Feb 2023 09:17


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