Mycobacterium tuberculosis

Nowhere in these ancient communities of the Eurasian land mass, where it is so common and feared, is there a record of its beginning. Throughout history, it had always been there, a familiar evil, yet forever changing, formless, unknowable. Where other epidemics might last weeks or months, where even the bubonic plague would be marked forever afterwards by the year it reigned, the epidemics of tuberculosis would last whole centuries and even multiples of centuries. Tuberculosis rose slowly, silently, seeping into homes of millions, like an ageless miasma. And once arrived, it never went away again. Year after year, century after century, it tightened its relentless hold, worsening whenever war or famine reduced the peoples' resistance, infecting virtually everybody, inexplicably sparing some while destroying others, bringing the young down onto their sickbeds, where the flesh slowly fell from their bones and they were consumed in the years-long fever, their minds brilliantly alert until, in apocalyptic numbers, they died, like the fallen leaves of a dreadful and premature autumn.

In 1996 TIGR was the recipient of a grant from the NIH to sequence the 4.4 Mb genome of Mycobacterium tuberculosis. While a similar project was underway to sequence the laboratory strain (H37Rv) at the Sanger Center (Cole et al. (1998). Nature. 393:537-544.), TIGR chose to sequence a recent clinical isolate from the Kentucky/Tennessee region (Valway et al. (1998). The New England J. of Med. 338:633-639. This strain (often referred to as the "Oshkosh" strain, but more properly CDC-1551) was isolated from a male children's clothing factory worker and was shown to be highly contagious, infecting approximately 80% of his co-workers and social contacts. The CDC-1551 strain was also demonstrated to be highly virulent in mice, producing several orders of magnitude more organisms than the H37Rv strain when inoculated into the lungs of mice. Fortunately, the strain has not caused wide-spread disease in man and is pan-drug sensitive. Undertaking the sequencing of this strain of TB has offers a unique opportunity to compare two closely related strains of the same pathogen whose level of virulence may be quite different (Fleischmann et al. Manuscript in Preparation).