Genetic profiling of Mycobacterium tuberculosis “modern” Beijing strains from Southwest Colombia

biorxiv(2019)

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摘要
Beijing strains of (lineage2) have been associated with drug-resistance and transmission of tuberculosis worldwide. Most of the Beijing strains identified in the Colombian pacific coast exhibited a multidrug resistant (MDR) phenotype, in contrast with the phenotype observed in Beijing isolates from other South-American countries. We wanted to evaluate the clonality and genetic background of the Beijing strains isolated in Colombia that belong mostly to the spoligo-international type (SIT) 190. Out of 37 Beijing stains characterized in an 8-years period, we identified five Beijing clones; 36 that belong to the SIT190 type and only one to SIT1. Two loci in VNTR typing: MIRU 39 and QUB11b exhibited the highest level of variation among these strains. Out of the 37 Beijing strains, only one was drug susceptible, 28 represented MDR-TB, four extensively drug resistant TB (XDR-TB) and four pre-XDR-TB. The mutations S531L and S315T1 were the most common among the MDR strains as reported elsewhere. Whole genome sequencing analysis allowed us to classify them as modern lineage Beijing strains, sharing up to 76 out of the 275 SNPs described in Beijing strains, as identified worldwide by Schürch including 54 non-synonymous SNPs and 23 silent mutations. We were also able to confirm the presence of 8 specific SNPs that were so far only found in the Beijing strains from Colombia. The presence of modern Beijing strains, most of them representing MDR-TB, suggests a different origin of this lineage compared to other Beijing strains found in neighboring countries, such as Peru. The specific 8-SNP signature confirmed the identity of these Colombian Beijing MDR strains. This work may serve as a genetic baseline to study the evolution and spread of Beijing strains in Colombia, which play an important role in the control of MDR-TB.
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