Protein Mass Spectrum Patterns of Bedaquiline-resistant strains through spontaneous mutation Using MALDI-TOF MS
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Abstract
WHO endorses Bedaquiline (BDQ) as Group A antituberculosis drugs for clinical practice. Rapid identification of drug-resistant MTB strains is crucial for optimizing treatment efficacy, preventing further transmission, and effectively controlling the spread of contagious tuberculosis. Matrix assisted laser desorption ionization time-of-flight Mass Spectrometry (MALDI-TOF MS) is the techniques applied to use for detection of antimicrobial resistance, including tuberculosis drug resistance. Therefore, there is a high probability that MALDI-TOF MS could generate specific mass spectrum patterns related to BDQ resistance. The aim of this study was to examine the pattern of protein mass spectra (PMS) between BDQ-spontaneous mutants derived from spontaneous mutation in M. tuberculosis H37Ra ATCC 25177 compared to H37Ra wild type using MALDI-TOF MS. A stepwise induced mutation was performed in M7H10 agar plate containing BDQ concentrations ranging from 0.125 to 1.00 µg/mL. The BDQ-resistant colonies exhibiting on M7H10 containing BDQ concentration between 0.50 and 1.00 µg/mL were used to study their protein mass spectrum patterns compared to H37Ra wild type via MALDI-TOF MS. The results revealed the presence of 6 spontaneous BDQR strains (H1-H6). MALDI-TOF MS analysis revealed that BDQR strains exhibited 6 significantly different PMS pattern compared to M. tuberculosis H37Ra WT. All BDQR strains displayed a significant decrease in the major mass spectra peak within the range of m/z 5688-5693. H1 exhibited an interesting minor MS peak increase in ranges 2733 and 4864-4865 m/z. In H3 and H5, there was a significant increase in the mass spectrum peak observed in the range of 4932-4933 m/z and 5332-5334 m/z. respectively. MSP dendrogram clearly distinguishes between each BDQR strain and the wild type. In conclusion, this study successfully distinguishes protein mass spectra between wild type and BDQR strains. MALDI-TOF MS has demonstrated reliability and holds potential as an alternative technique for detecting drug resistance in MTB.
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