Genomic Variability of Mycobacterium tuberculosis Strains of the Euro-American Lineage Based on Large Sequence Deletions and 15-Locus MIRU-VNTR Polymorphism

Abstract

A sample of 260 Mycobacterium tuberculosis strains assigned to the Euro-American family was studied to identify phylogenetically informative genomic regions of difference (RD). Mutually exclusive deletions of regions RD115, RD122, RD174, RD182, RD183, RD193, RD219, RD726 and RD761 were found in 202 strains; the RDRio deletion was detected exclusively among the RD174-deleted strains. Although certain deletions were found more frequently in certain spoligotype families (i.e., deletion RD115 in T and LAM, RD174 in LAM, RD182 in Haarlem, RD219 in T and RD726 in the “Cameroon” family), the RD-defined sublineages did not specifically match with spoligotype-defined families, thus arguing against the use of spoligotyping for establishing exact phylogenetic relationships between strains. Notably, when tested for katG463/gyrA95 polymorphism, all the RD-defined sublineages belonged to Principal Genotypic Group (PGG) 2, except sublineage RD219 exclusively belonging to PGG3; the 58 Euro-American strains with no deletion were of either PGG2 or 3. A representative sample of 197 isolates was then analyzed by standard 15-locus MIRU-VNTR typing, a suitable approach to independently assess genetic relationships among the strains. Analysis of the MIRU-VNTR typing results by using a minimum spanning tree (MST) and a classical dendrogram showed groupings that were largely concordant with those obtained by RD-based analysis. Isolates of a given RD profile show, in addition to closely related MIRU-VNTR profiles, related spoligotype profiles that can serve as a basis for better spoligotype-based classification.

Genetic diversity of Mycobacterium tuberculosis clinical isolates in Blantyre, Malawi

“…Globally, 7 major lineages of Mtb have been defined and 4 of these were detected as circulating in Blantyre. The Euro-American lineage (lineage 4) is the most predominant of the Mtb lineages in Europe and America but has specific sub-lineages dominating in Africa [20, 22]. Results in this study and those done previously in Malawi [8, 13] demonstrate complete concordance with those done in this region of Africa [23].…”

A rapid, standardized protein extraction method using adaptive focused acoustics for identification of mycobacteria by MALDI-ToF MS

“…This suggests it may be possible for clinical laboratories to utilize the existing commercial database in conjunction with the optimized AFA protocol and only modify the library when clinical strains for which log confidence scores of < 1.7 are obtained so long as the spectra generated are consistent with the correct identification. Such strain-to-strain variation based on the geographical location from which they were derived has been previously documented for M. tuberculosis(20,21).…”

First insight into the genetic population structure of Mycobacterium tuberculosis isolated from pulmonary tuberculosis patients in Egypt

“…It is worth mentioning that MTB strains circulating in this governorate were seemingly transmitted from patient to patient. In contrast, all isolates belonging to the spoligotype-defined SIT4 were completely discriminated from each other a long period of time that resulted in successively established strains stably associating with the Egyptian population[9].Comparative analyses were performed between our data and those reported from others countries based on MIRU-VNTR typing of MTB strains belonging to SIT53(Table 5)[18][19][20][21]33]. Locus Mtub21 was highly conserved in Egyptian MTB strains belonging to SIT53 and showed poor discrimination with HGDI = 0.0384 in the same manner as the isolates belonging to SIT34 and SIT4 with one repeat unit.…”