Universidad Santiago de Cali, Cali, Colombia.
Departamento de Salud Pública y Medicina Comunitaria, Universidad Icesi, Cali, Colombia.
PLoS One. 2020 Apr 24;15(4):e0224908. doi: 10.1371/journal.pone.0224908. eCollection 2020.
Beijing strains of Mycobacterium tuberculosis (lineage 2) have been associated with drug-resistance and transmission of tuberculosis worldwide. Most of the Beijing strains identified in the Colombian Pacific coast have exhibited a multidrug resistant (MDR) phenotype. We sought to evaluate the clonality and sublineage of Beijing strains circulating in Southwestern Colombia. Thirty-seven Beijing strains were identified through spoligotyping out of 311 clinical isolates collected in 9 years from 2002-2010. Further analysis by MIRU-VNTR 24 loci was conducted for the Beijing strains. For sublineage classification, deletions of RD105, RD207, and RD131 and point mutations at fbpB, mutT2, and acs were evaluated. Drug-resistance associated mutations to first- and second-line anti-TB drugs were also evaluated. Additionally, two Beijing strains were Illumina-whole genome sequenced (one MDR and one drug-susceptible). Among the 37 Beijing strains characterized, 36 belonged to the SIT190 type from which 28 were MDR, four pre-extensively drug resistant (XDR) TB, and four XDR-TB. The remaining strain was SIT1 and drug susceptible. MIRU-VNTR analysis allowed the identification of three Beijing clusters and two unique strains. Beijing strains were confirmed as "modern" sublineage. The mutations rpoB S531L and katG S315T were the most common among MDR strains. Moreover, the two strains evaluated by whole genome sequencing (WGS) shared most of the genetic features with the sublineage 2.2.1 "modern" Beijing previously characterized from Asian strains. WGS analysis of the MDR strain revealed the presence of eight SNPs previously reported in other MDR "Beijing-like" strains from Colombia. The presence of "modern" Beijing strains in Southwestern Colombia, most of them with MDR phenotype, suggests a different origin of this M. tuberculosis sublineage compared to other Beijing strains found in neighboring South American countries. This work may serve as a genetic baseline to study the evolution and spread of M. tuberculosis Beijing strains in Colombia, which play an important role in the propagation of MDR-TB.
北京分枝杆菌(谱系 2)已与全球范围内的结核病耐药性和传播有关。在哥伦比亚太平洋海岸发现的大多数北京菌株都表现出多药耐药(MDR)表型。我们试图评估在哥伦比亚西南部流行的北京菌株的克隆性和亚谱系。在 2002 年至 2010 年的 9 年间,从 311 例临床分离株中通过 spoligotyping 鉴定出 37 株北京菌株。对北京菌株进一步进行了 24 个 MIRU-VNTR 位点的分析。对于亚谱系分类,评估了 RD105、RD207 和 RD131 的缺失以及 fbpB、mutT2 和 acs 的点突变。还评估了与一线和二线抗结核药物耐药相关的突变。此外,对两株北京菌株进行了 Illumina 全基因组测序(一株 MDR 和一株药物敏感)。在所鉴定的 37 株北京菌株中,36 株属于 SIT190 型,其中 28 株为 MDR、4 株为预广泛耐药(XDR)TB、4 株为 XDR-TB。其余一株为 SIT1 且药物敏感。MIRU-VNTR 分析确定了三个北京簇和两个独特的菌株。北京菌株被确认为“现代”亚谱系。rpoB S531L 和 katG S315T 突变是 MDR 菌株中最常见的突变。此外,通过全基因组测序(WGS)评估的两株菌株与以前从亚洲菌株中鉴定的亚谱系 2.2.1“现代”北京菌株共享大多数遗传特征。对 MDR 菌株的 WGS 分析显示了以前在哥伦比亚其他 MDR“北京样”菌株中报道的 8 个 SNPs 的存在。在哥伦比亚西南部发现的“现代”北京菌株,其中大多数表现出 MDR 表型,这表明与在邻国南美洲国家发现的其他北京菌株相比,该结核分枝杆菌亚谱系的起源不同。这项工作可以作为研究 M. tuberculosis 北京菌株在哥伦比亚的进化和传播的遗传基础,它们在传播 MDR-TB 方面发挥着重要作用。