RT Journal Article T1 Systematic survey of clonal complexity in tuberculosis at a populational level and detailed characterization of the isolates involved. A1 Navarro, Yurena A1 Herranz, Marta A1 Pérez-Lago, Laura A1 Martínez Lirola, Miguel A1 Ruiz-Serrano, Maria Jesús A1 Bouza, Emilio A1 García de Viedma, Darío K1 Antígenos Bacterianos K1 Hidrolasas de Éster Carboxílico K1 Elementos Transponibles de ADN K1 ADN Bacteriano K1 Genotipo K1 Tipificación Molecular K1 Mycobacterium tuberculosis K1 Polimorfismo de Longitud del Fragmento de Restricción K1 Tuberculosis AB Clonally complex infections by Mycobacterium tuberculosis are progressively more accepted. Studies of their dimension in epidemiological scenarios where the infective pressure is not high are scarce. Our study systematically searched for clonally complex infections (mixed infections by more than one strain and simultaneous presence of clonal variants) by applying mycobacterial interspersed repetitive-unit (MIRU)-variable-number tandem-repeat (VNTR) analysis to M. tuberculosis isolates from two population-based samples of respiratory (703 cases) and respiratory-extrapulmonary (R+E) tuberculosis (TB) cases (71 cases) in a context of moderate TB incidence. Clonally complex infections were found in 11 (1.6%) of the respiratory TB cases and in 10 (14.1%) of those with R+E TB. Among the 21 cases with clonally complex TB, 9 were infected by 2 independent strains and the remaining 12 showed the simultaneous presence of 2 to 3 clonal variants. For the 10 R+E TB cases with clonally complex infections, compartmentalization (different compositions of strains/clonal variants in independent infected sites) was found in 9 of them. All the strains/clonal variants were also genotyped by IS6110-based restriction fragment length polymorphism analysis, which split two MIRU-defined clonal variants, although in general, it showed a lower discriminatory power to identify the clonal heterogeneity revealed by MIRU-VNTR analysis. The comparative analysis of IS6110 insertion sites between coinfecting clonal variants showed differences in the genes coding for a cutinase, a PPE family protein, and two conserved hypothetical proteins. Diagnostic delay, existence of previous TB, risk for overexposure, and clustered/orphan status of the involved strains were analyzed to propose possible explanations for the cases with clonally complex infections. Our study characterizes in detail all the clonally complex infections by M. tuberculosis found in a systematic survey and contributes to the characterization that these phenomena can be found to an extent higher than expected, even in an unselected population-based sample lacking high infective pressure. PB American Society for Microbiology SN 0095-1137 YR 2011 FD 2011-12-28 LK http://hdl.handle.net/10668/733 UL http://hdl.handle.net/10668/733 LA en NO Navarro Y, Herranz M, Pérez-Lago L, Martínez Lirola M, Ruiz-Serrano MJ, Bouza E, et al. Systematic survey of clonal complexity in tuberculosis at a populational level and detailed characterization of the isolates involved. J. Clin. Microbiol.. 2011; 49(12):4131-7 DS RISalud RD Apr 10, 2025