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European Society of Mycobacteriology - Instituto Nacional de Saúde ...

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OP-20<br />

GROWTH PROFILE OF CLINICAL ISOLATES OF Mycobacterium<br />

tuberculosis COMPLEX IN MURINE MACROPGHAGES<br />

Susanne Homolka 1 , Stefan Niemann 1 , David G. Russell 2 and Kyle H. Roh<strong>de</strong> 2<br />

1 - Molecular <strong>Mycobacteriology</strong>, National Reference Center <strong>of</strong> Mycobacteria, Borstel Germany<br />

2 - Department <strong>of</strong> Microbiology/Immunology, Cornell University, Vet. Med. Center, Ithaca, USA<br />

Background<br />

Mycobacterium tuberculosis and other members <strong>of</strong> the Mycobacterium tuberculosis complex (MTC) remain a major cause <strong>of</strong><br />

morbidity and mortality worldwi<strong>de</strong>. Several studies based on spoligotyping, IS6110 fingerprinting and MIRU-VNTR typing<br />

<strong>de</strong>monstrated that the global population structure <strong>of</strong> MTC is <strong>de</strong>fined by phylogeographical lineages and genotypes that are<br />

also associated with pathogenic differences. However, the influence <strong>of</strong> strain genomic variation on the outcome <strong>of</strong> infection<br />

and the clinical presentation are not completely un<strong>de</strong>rstood. In our study, we investigated growth differences <strong>of</strong> 15 strains<br />

<strong>of</strong> five different genotypes in comparison to the CDC1551 reference strains in liquid culture and in macrophages.<br />

Methods<br />

Murine bone marrow <strong>de</strong>rived macrophages were infected with liquid culture <strong>of</strong> different clinical isolates (MOI 3:1;<br />

2x10 6 CFU/ml). Survival <strong>of</strong> strains in resting and activated macrophages was <strong>de</strong>termined at different time points up to 11<br />

days post-infection. Additionally, growth kinetics <strong>of</strong> all strains in 7H9 liquid media were analyzed.<br />

Results<br />

Growth analyses <strong>of</strong> clinical isolates in liquid culture based on OD measurements showed no significant differences in<br />

comparison to CDC1551. However, we observed both strain- and genotype-specific survival and growth pr<strong>of</strong>iles within<br />

resting and activated macrophages.<br />

Conclusions<br />

The genomic diversity <strong>of</strong> clinical isolates influences the complex interaction <strong>of</strong> the pathogen with host phagocytes.<br />

Further analyses to correlate intracellular gene expression pr<strong>of</strong>iles with the outcome <strong>of</strong> infection are in progress.<br />

62 ESM 2009

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