Phylogeographic, immunological and growth features of Argentinean epidemic MDR TB strains

RITACCO V; SASIAIN MC; LOPEZ B; DE LA BARRERA S; VAN GROLL A; PALOMINO JC; BARRERA L

Simposio; V Reunión de la Sociedad Latinoamericana de Tuberculosis y otras Micobacterias (SLAMTB); 2010

Systematic countrywide surveillance of multidrug resistance tuberculosis (MDR TB) is being carried out in Argentina since 2003. Mycobacterium tuberculosis IS6110 RFLP DNA fingerprinting and spoligotyping are performed on strains isolated from all new MDR TB cases whose drug susceptibility tests are done or confirmed at the national reference TB laboratory, Instituto Malbran. Genotype analysis shows that: i) lineages formerly associated to MDR TB transmission in Argentina still prevail over other MDR TB strains circulating in the country; ii) there is a strong association of the most conspicuous MDR genotypes with the geographical niches where they first emerged; and iii) the so-called strain M, a local strain of the Haarlem 2 sub-lineage, which otherwise is highly infrequent in our setting, is overrepresented among new cases of MDR and XDR TB. The epidemiological fitness of this strain is supported by results of in vitro strain competition experiments but does not correlate with in vitro growth kinetic studies or virulence in experimentally infected human monocyte-derived macrophages. Strain M is a poor inducer of macrophage apoptosis and cytotoxic T-lymphocyte activity, two features that could serve as evasion mechanisms. In sum, strain M has a singular ability to build up drug resistance without impairing the ability to spread in the community. This success could be related with its ability to elicit a distinct strategy when interacting with host cells.