| Summary: | <p>Abstract</p> <p>Background</p> <p>The ability of <it>Mycobacterium tuberculosis</it> to survive and replicate in macrophages is crucial for the mycobacterium's ability to infect the host and cause tuberculosis. To identify <it>Mycobacterium tuberculosis</it> genes involved in survival in macrophages, a library of non-pathogenic <it>Mycobacterium smegmatis</it> bacteria, each carrying an individual integrated cosmid containing <it>M. tuberculosis</it> H37Rv genomic DNA, was passed through THP-1 human macrophages three times.</p> <p>Results</p> <p>Two of the clones recovered from this enrichment process, sur2 and sur3, exhibited significantly increased survival relative to wild-type bacteria. In coinfection experiments, the ratio of sur2 colonies to wild-type colonies was 1:1 at 0 hours but increased to 20:1 at 24 hours post phagocytosis. The ratio of sur3 colonies to wild-type colonies was 1:1 at 0 hours and 5:1 at 24 hours. The <it>M. tuberculosis</it> ORFs responsible for increased survival were shown to be <it>Rv0365c</it> for the sur2 clone and <it>Rv2235</it> for the sur3 clone. These ORFs encode proteins with as-of-yet unknown functions.</p> <p>Conclusions</p> <p>We identified two <it>M. tuberculosis</it> ORFs which may be involved in the ability of tubercle bacilli to survive in macrophages.</p>
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