Jo Kyung-Wook, Lee Soyeon, Kang Mi Ran, Sung Heungsup, Kim Mi-Na, Shim Tae Sun
Division of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
YD R&D Center, YD Diagnostics, Yongin, Korea.
Tuberc Respir Dis (Seoul). 2017 Jul;80(3):270-276. doi: 10.4046/trd.2017.80.3.270. Epub 2017 Jul 3.
A disputed mutation is a specific type of mutation that can cause low-level resistances to rifampin (RIF). Here, we aimed to assess the frequency and types of disputed mutations in isolates from South Korea.
Between August 2009 and December 2015, 130 patients exhibited RIF resistance on the MTBDR assay at Asan Medical Center. Among these cases, we identified the strains with disputed mutation by sequencing analysis, as well as among the strains from the International Tuberculosis Research Center (ITRC).
Among our cases, disputed mutations led to RIF resistance in at least 6.9% (9/130) of the strains that also exhibited RIF resistance on the MTBDR assay. Moreover, at the ITRC, sequencing of the gene of 170 strains with the mutation indicated that 23 strains (13.5%) had the disputed mutations. By combining the findings from the 32 strains from our center and the ITRC, we identified the type of disputed mutation as follows: CTG511CCG (L511P, n=8), GAC516TAC (D516Y, n=8), CTG533CCG (L533P, n=8), CAC526CTC (H526L, n=4), CAC526AAC (H526N, n=3), and ATG515GTG (M515V, n=1).
Disputed mutations do not seem to be rare among the strains exhibiting RIF resistance in South Korea.
争议性突变是一种特定类型的突变,可导致对利福平(RIF)产生低水平耐药性。在此,我们旨在评估韩国分离株中争议性突变的频率和类型。
2009年8月至2015年12月期间,130例患者在峨山医学中心的MTBDR检测中表现出对RIF耐药。在这些病例中,我们通过测序分析确定了具有争议性突变的菌株,以及国际结核病研究中心(ITRC)的菌株。
在我们的病例中,争议性突变导致至少6.9%(9/130)的菌株对RIF耐药,这些菌株在MTBDR检测中也表现出对RIF耐药。此外,在ITRC,对170株具有该突变的菌株的基因进行测序表明,23株(13.5%)有争议性突变。通过合并我们中心和ITRC的32株菌株的研究结果,我们确定了争议性突变的类型如下:CTG511CCG(L511P,n = 8)、GAC516TAC(D516Y,n = 8)、CTG533CCG(L533P, n = 8)、CAC526CTC(H526L,n = 4)、CAC526AAC(H526N,n = 3)和ATG515GTG(M515V,n = 1)。
在韩国表现出对RIF耐药的菌株中,争议性突变似乎并不罕见。