Navarro, YurenaHerranz, MartaPérez-Lago, LauraMartínez Lirola, MiguelRuiz-Serrano, Maria JesúsBouza, EmilioGarcía de Viedma, Darío2013-01-112013-01-112011-12-28Navarro 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):4131-70095-1137http://hdl.handle.net/10668/733Clonally 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.enAntígenos BacterianosHidrolasas de Éster CarboxílicoElementos Transponibles de ADNADN BacterianoGenotipoTipificación MolecularMycobacterium tuberculosisPolimorfismo de Longitud del Fragmento de RestricciónTuberculosisMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Esterases::Carboxylic Ester HydrolasesMedical Subject Headings::Diseases::Virus Diseases::CoinfectionMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Interspersed Repetitive Sequences::DNA Transposable ElementsMedical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::DNA::DNA, BacterialMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::GenotypeMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Molecular TypingMedical Subject Headings::Organisms::Bacteria::Gram-Positive Bacteria::Gram-Positive Rods::Gram-Positive Asporogenous Rods::Gram-Positive Asporogenous Rods, Regular::Mycobacteriaceae::Mycobacterium::Mycobacterium tuberculosisMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Restriction Fragment LengthMedical Subject Headings::Health Care::Environment and Public Health::Public Health::Epidemiologic Methods::Data Collection::Vital Statistics::Morbidity::PrevalenceMedical Subject Headings::Diseases::Bacterial Infections and Mycoses::Bacterial Infections::Gram-Positive Bacterial Infections::Actinomycetales Infections::Mycobacterium Infections::TuberculosisMedical Subject Headings::Chemicals and Drugs::Biological Factors::Antigens::Antigens, Bacterialresearch article21956991open access10.1128/JCM.05203-111098-660X