First evaluation of drug-resistant Mycobacterium tuberculosis clinical isolates from Congo revealed misdetection of fluoroquinolone resistance by line probe assay due to a double substitution T80A-A90G in GyrA.
First evaluation of drug-resistant Mycobacterium tuberculosis clinical isolates from Congo revealed misdetection of fluoroquinolone resistance by line probe assay due to a double substitution T80A-A90G in GyrA.
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DOI：
10.1371/journal.pone.0095083
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Lemaître N
中科院分区：
文献类型：
--
作者：
Aubry A;Sougakoff W;Bodzongo P;Delcroix G;Armand S;Millot G;Jarlier V;Courcol R;Lemaître N
结核病是刚果主要的公共卫生问题之一。然而，由于处理能力不足，缺乏有关结核分枝杆菌耐药性的数据。因此，本研究的目的是首次调查M.的耐药模式和菌株谱系。在刚果的两个主要城市收集的结核复合菌（MTBC）分离株。在为期9天的时间内，从布拉柴维尔和黑角的结核病诊断和治疗中心的114名患者中分离出114例涂片阳性的结核菌，进行培养和药物敏感性试验（DST）。通过使用线性探针测定（GenoType MTBDRplus和MTBDRsl）和DNA测序来进行赋予耐药性的突变的检测。通过MIRU-VNTR基因分型确定菌株谱系。在114例结核分枝杆菌中，46例结核分枝杆菌培养阳性。21例（46%）对一种或多种一线抗结核药物耐药。其中15例（71%）为多药耐药（MDR）。MTBDRplus检测试剂盒能很好地检测出利福平和异烟肼耐药相关的最常见突变，分别为rpoB中的D516 V（60%）和katG中的S315 T（87%）。15株耐药菌株均对氟喹诺酮类和注射用二线药物敏感。通过MTBDRs 1测定和DNA测序，在涉及对阿米卡星和卷曲霉素的抗性的rrs基因座中未检测到突变。相比之下，由于GyrA中存在T80 A-A90 G双取代，属于与T家族相关的同一簇的9个MDR菌株通过MTBDRsl测定被鉴定为对氟喹诺酮假耐药。总之，这些数据揭示了特定MDR克隆在刚果中的可能传播，其通过MTBDR 1测定被错误鉴定为氟喹诺酮耐药。因此，该试验不能取代金标准培养法，应根据患者的籍贯仔细解释。
Tuberculosis (TB) is one of the major public health problems in Congo. However, data concerning Mycobacterium tuberculosis drug resistance are lacking because of the insufficient processing capacity. So, the aim of this study was to investigate for the first time the resistance patterns and the strain lineages of a sample of M. tuberculosis complex (MTBC) isolates collected in the two main cities of Congo. Over a 9-day period, 114 smear-positive sputa isolated from 114 patients attending centers for the diagnosis and treatment of TB in Brazzaville and Pointe Noire were collected for culture and drug susceptibility testing (DST). Detection of mutations conferring drug resistance was performed by using line probe assays (GenoType MTBDRplus and MTBDRsl) and DNA sequencing. Strain lineages were determined by MIRU-VNTR genotyping. Of the 114 sputa, 46 were culture positive for MTBC. Twenty-one (46%) were resistant to one or more first-line antiTB drugs. Of these, 15 (71%) were multidrug resistant (MDR). The most prevalent mutations involved in rifampin and isoniazid resistance, D516V (60%) in rpoB and S315T (87%) in katG respectively, were well detected by MTBDRplus assay. All the 15 MDR strains were susceptible to fluoroquinolone and injectable second-line drug. No mutation was detected in the rrs locus involved in resistance to amikacin and capreomycin by both the MTBDRsl assay and DNA sequencing. By contrast, 9 MDR strains belonging to the same cluster related to T-family were identified as being falsely resistant to fluoroquinolone by the MTBDRsl assay due to the presence of a double substitution T80A-A90G in GyrA. Taken together, these data revealed a possible spread of a particular MDR clone in Congo, misidentified as fluoroquinolone resistant by MTBDRsl assay. Thus, this test cannot replace gold-standard culture method and should be interpreted carefully in view of the patient's native land.
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影响因子：
3.7
作者：
Mpagama SG;Houpt ER;Stroup S;Kumburu H;Gratz J;Kibiki GS;Heysell SK
通讯作者：
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作者：
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作者：
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