Spoligotype-Based Comparative Population Structure Analysis of Multidrug-Resistant and Isoniazid-Monoresistant Mycobacterium tuberculosis Complex Clinical Isolates in Poland

Abstract

The spoligotyping-based population structure of multidrug-resistant (MDR) Mycobacterium tuberculosis strains isolated in Poland (n ‫؍‬ 46), representing all culture-positive MDR tuberculosis (MDR-TB) cases, was compared to that of isoniazid (INH)-monoresistant strains (n ‫؍‬ 71) isolated in 2004. The latter data set from a previous study (E. Augustynowicz-Kopeć, T. Jagielski, and Z. Zwolska, J. Clin. Microbiol. 2008, 46:4041-4044) represented 87% of all INH-monoresistant strains. The clustering rates and genotypic-diversity indexes for the 2 subpopulations were not significantly different (P ‫؍‬ 0.05). The results were entered in the SITVIT2 database to assign specific shared type designations, corresponding genotypic lineages, and geographical distributions and compared to available data from neighboring countries (Germany, n ‫؍‬ 704; Czech Republic, n ‫؍‬ 530; Sweden, n ‫؍‬ 379; Kaliningrad, Russia, n ‫؍‬ 90) and strains from previous studies in Poland (n ‫؍‬ 317). MDR strains resulted in 27 patterns (20 unique strains within the study and 7 clusters containing 2 to 6 isolates per cluster with a clustering rate of 56.5%) and belonged to the following genotypic lineages: ill-defined T family (28.3%), Haarlem (17.4%), Latin American and Mediterranean (LAM) (13%), Beijing (8.7%), S family (4.35%), and the X clade (2.17%). Comparison of the genetic structure of the MDR strains with that of INH-monoresistant strains showed that a total of 9 patterns were shared by both groups; these represented 1/3 of the MDR strains and 2/3 of the INH-monoresistant strains. Interestingly, 76.1% of the MDR isolates and 71.8% of the INH-resistant isolates yielded spoligotypes that were previously reported from Poland. The observation that nearly half of the spoligotypes identified among both MDR (48.1%) and INH-monoresistant (43.3%) M. tuberculosis isolates were present in Poland's neighboring countries suggested that a significant proportion of MDR and INH-resistant TB cases in Poland were caused by strains actively circulating in Poland or its neighbors. Our results corroborate the leading role of the T and Haarlem genotypes in the epidemiology of drug-resistant TB in Poland. Nevertheless, the LAM and Beijing family strains that infected, correspondingly, 13% and 9% of patients with MDR-TB were absent among the strains from patients with INHmonoresistant TB, suggesting that a proportion of MDR-TB cases in Poland are due to ongoing transmission of MDR clones exhibiting specific genotypes. Study of the population genetic relationships between MDR and INH-monoresistant strains by drawing minimum spanning trees showed that ill-defined T1 sublineage strains (1/3 of all INH-monoresistant strains), represented by its prototype, SIT53, constituted the central node of the tree, followed by strains belonging to the well-defined H3, H1, and S subgroups. However, the MDR group, in addition, contained LAM (n ‫؍‬ 6) and Beijing (n ‫؍‬ 4) lineage isolates. With the exception of the 4 Beijing lineage strains in the latter group and a single orpha...

Inadequacies of Minimum Spanning Trees in Molecular Epidemiology

“…We therefore considered data from a survey of prior publications (1,3,11,13,16,17,19,(22)(23)(24) where MSTs had been used to draw inferences about population structure from various data, including spoligotypes, VNTRs, DNA sequences, and multilocus sequence types (MLST).…”

Mycobacterium tuberculosis of the RD Rio Genotype Is the Predominant Cause of Tuberculosis and Associated with Multidrug Resistance in Porto Alegre City, South Brazil

“…Despite its success, little is yet known about the epidemiology, biological behavior, and clinical attributes of disease caused by strains of the LAM family. Similar to Beijing family strains, members of the LAM family have also been associated with drug resistance and outbreaks (13)(14)(15)(16), including the recent description of a LAM strain as the leading cause of XDR-TB in South Africa (17).…”

Tuberculose Multirresistente por Estirpes da Família Beijing, em Doentes de Lisboa, Portugal: Estudo Preliminar

“…10,11,15,23 Entretanto, na região de Lisboa desconhece-se o que possa ter acontecido com estas estirpes, nomeadamente, nos primeiros anos da epidemia de TB MR, em que predominavam os co-infectados por VIH, os UDI, a TB MR secundária à má adesão ao tratamento e a família Lisboa. 36,38 Nos cinco doentes do estudo não identificámos quaisquer manifestações clínicas ou sinais radiológicos, que fossem atributos da TB causada por esta família Beijing quer nos doentes imunocompetentes, quer no co-infectado por VIH, todos eles com TB pulmonar, contudo é de salientar a frequência das cavitações.…”

“…23 (TB TR). 25 A distribuição mundial desta família é impressionante, continuando por esclarecer as suas características intrínsecas e os respectivos factores ambientais ou do hospedeiro que a definem.…”