<p>Distribution and Frequency of <em>rpo</em>B Mutations Detected by Xpert MTB/RIF Assay Among Beijing and Non-Beijing Rifampicin Resistant <em>Mycobacterium tuberculosis</em> Isolates in Bangladesh</p>

Abstract

Background: Rifampicin resistance (RR) is a key indicator of multidrug-resistant tuberculosis (MDR-TB) and 95% of the RR is associated with the mutation in the 81-bp rifampicin resistance determining region (RRDR) of the rpoB gene of Mycobacterium tuberculosis complex (MTBC). The Xpert MTB/RIF (Xpert) assay uses five overlapping molecular beacon probes (A-E) complementary to RRDR region that detect MTBC and mutations associated with RR. The objective of the study was to investigate the distribution and frequency of mutations detected by Xpert assay among Beijing and non-Beijing RR-TB isolates. Methods: A total of 205 randomly selected RR-TB specimens detected by Xpert assay were included in this study. A portion of specimens was further subjected to culture, MTBDRplus test and the positive culture isolates were genotyped by spoligotyping. Results: We found that the most frequent mutation occurred at probe E (S531L) binding region in both Beijing and non-Beijing isolates (61.9% and 66.9%, respectively). The Beijing family had higher mutation rates than non-Beijing (19.0% vs 12.4%) at probe B (D516V) while the non-Beijing family had higher mutations at probe D (H526D or H526Y) than the Beijing (13.2% vs 10.7%) family. Mutations at probes Aand C were less common in both Beijing and non-Beijing isolates. There was no significant difference (P=0.36) in the occurrence of mutations at different probes between Beijing and non-Beijing isolates. Conclusions: The study results revealed that the most frequent mutation occurs in the region of probe E and the least common mutations at probe A and C among both Beijing and non-Beijing RR-TB cases. This first insight into the probe mutation variation and frequencies among the RR-TB cases in Bangladesh forms the baseline information for further investigation.

Frequency and Distribution of Rifampicin Resistance in Mycobacterium Tuberculosis Clinical Isolates Using Gene Xpert MTB/RIF in Delta State, South-South Nigeria

“…We reviewed 16 rifampicinresistant cases while Uddin et al, worked with 205 samples. We reported no probe mutation associated with probe A and just one probe mutation associated with probe C. This report agrees with the findings of Uddin et al, who reported reduced frequency for mutations at both probes 10 . It is worthy to note that all probe D region associated mutation occurs for the female participants and those within the age grade of 31-50 years.…”

“…This figure is higher than the 6.0% reported by Alemu et al 21 , but similar to the report of Diande et al 24 . Uddin et al 10 , reported probe E as the probe associated with the highest frequency of RR-TB for all age and sex category. This finding is in contrast to our report.…”

“…The probes are A (codon 507-511), B (codon 512-518), C (codon 518-523), D (codon 523-529) and E (codon 529-533) 9 . A strain is termed resistant when one or more of the probes fail to hybridize or when the difference between the first and last cycle threshold (ct) is more than 3.5 10 . The distribution and frequency of mutations along the rpoB gene vary for different geographical regions.…”

Performance Assessment of Xpert MTB/RIF Assay for Detecting Pulmonary Tuberculosis and Rifampin Resistance in a Tertiary Care Hospital in Korea

“…Resistant causing probe distribution varies by geographical region. For example, dropout of probe E caused rifampin resistance in 64.9 % (133/205) in a Bangladeshi study (33) and 77.0 % (314/408) in a Pakistan study (34). Meanwhile, in American study, main probes for rifampin resistance were both probe E (37.0 %) and also probe D (34.1 %) (35).…”

Application of Computational Methods in Understanding Mutations in Mycobacterium tuberculosis Drug Resistance

“…Similarly, resistance to rifampicin, a key component in the first-line treatment of TB that binds to the β subunit of RNA polymerase, has been linked to mutations in a region of the 81 bp region of the rpoB gene. Whilst the gene encodes for the β subunit of RNA polymerase, rifampicin resistance is mostly due to mutations at positions 516, 526, and 531 ( Goldstein, 2014 ; Uddin et al, 2020 ). This is achieved by inhibition of elongation of the messenger RNA, which interferes with transcription ( Uddin et al, 2020 ).…”