Uddin Mohammad Khaja Mafij, Rahman Arfatur, Ather Md Fahim, Ahmed Tanvir, Rahman Syed Mohammad Mazidur, Ahmed Shahriar, Banu Sayera
Infectious Diseases Division, icddr,b, Dhaka, Bangladesh.
Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), Parkville VIC 3052, Australia.
Infect Drug Resist. 2020 Mar 10;13:789-797. doi: 10.2147/IDR.S240408. eCollection 2020.
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 gene of 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.
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, MTBDR test and the positive culture isolates were genotyped by spoligotyping.
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 (=0.36) in the occurrence of mutations at different probes between Beijing and non-Beijing isolates.
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.
利福平耐药(RR)是耐多药结核病(MDR-TB)的关键指标,95%的RR与结核分枝杆菌复合群(MTBC)基因81bp利福平耐药决定区(RRDR)的突变有关。Xpert MTB/RIF(Xpert)检测使用与RRDR区域互补的五个重叠分子信标探针(A-E)来检测MTBC及与RR相关的突变。本研究的目的是调查Xpert检测在北京和非北京RR-TB分离株中检测到的突变的分布和频率。
本研究纳入了205份随机选取的经Xpert检测的RR-TB标本。部分标本进一步进行培养、MTBDR检测,对阳性培养分离株进行间隔寡核苷酸分型。
我们发现,在北京和非北京分离株中,最常见的突变发生在探针E(S531L)结合区域(分别为61.9%和66.9%)。北京家族在探针B(D516V)处的突变率高于非北京家族(19.0%对12.4%),而非北京家族在探针D(H526D或H526Y)处的突变高于北京家族(13.2%对10.7%)。探针A和C处的突变在北京和非北京分离株中均较少见。北京和非北京分离株在不同探针处的突变发生率无显著差异(P=0.36)。
研究结果表明,在北京和非北京RR-TB病例中,最常见的突变发生在探针E区域,而探针A和C处的突变最少见。对孟加拉国RR-TB病例中探针突变变异和频率的这一初步了解为进一步研究奠定了基础信息。