Mycobacteria Make Spores?

by Peter Setlow

The title page of Robert Koch’s original article,
The Etiology of Tuberculosis, published in the
Berliner Klinische Wochenschrift, April 10, 1882.

Rarely does news come along that threatens to overturn our cherished beliefs. Since early after the discovery of tubercle bacilli by Robert Koch in 1882, the mycobacteria have been considered not to be spore formers. Now this is being challenged by a new report.

The genus Mycobacterium encompasses a number of major human pathogens including M. tuberculosis, among the most common pathogens carried by humans. A hallmark of M. tuberculosis infections is the ability of the organism to persist asymptomatically for long periods in the host, and then reappear and cause disease. The new paper by Ghosh et al. from Uppsala University in Sweden claims that members of some Mycobacterium species form spores that resemble those produced by well-studied Bacillus species. The authors worked primarily with M. marinum, a relatively fast-growing mycobacterium with a doubling time of 4-6 hours. In old cultures they observed forms that resembled spores not only in their morphology and their resistance, but also in their accumulation of dipicolinic acid, a signature molecule associated with spores of Bacillus species. Putative spores were also observed in old M. bovis cultures. In addition, they found that Mycobacterium genomes, including that of M. tuberculosis, contain homologs of genes important for sporulation of the model spore former, Bacillus subtilis. At least some of these genes were transcribed only in old M. marinum cultures.

Robert Koch (1843–1910),
discovered Mycobac-
terium tuberculosis, 1882.

These observations would certainly be a paradigm shift in Mycobacterium biology, particularly regarding our thoughts about the reasons for the latency of mycobacterial infections. Given the revolutionary implications of these conclusions, it is obviously imperative that a high standard of proof be applied to such work. This is of special concern for the mycobacteria, since these organisms grow more slowly than many Bacillus species (doubling times of ~30 min); consequently, the potential for contamination of old cultures with a much faster growing known spore former is a major concern. The authors have done a variety of control experiments to establish that the spores formed in their cultures are indeed from M. marinum rather than some contaminating known spore former, but skepticism about such a novel finding will certainly not be (and indeed should not be!) obviated by this first report. One would expect that this work will be rapidly replicated and extended in other labs, including analysis of the DNA in the purified spores and examination of additional Mycobacterium species for spore formation. If their conclusion that mycobacteria are indeed spore-formers holds up, it will truly be a paradigm shift. It will be fascinating to watch this story unfold, with either the confirmation or refutation of this initial report.

Peter Setlow is Professor of Molecular, Microbial and Structural Biology at the University of Connecticut in Farmington, CT. The sparkly young lady to his right is granddaughter Anne.

Comments

[Jaydip Ghosh]

Very nice article, thoughtful and objective.
I grew up in India. Back in the forties and fifties, some of my relatives died in TB. When I was a kid (in the seventies to early eighties) I heared people saying that the "germ" of TB is not destroyed even if the body of person died in TB is cremated (burnt to ashes). Moreover, they used to say that the TB "germ" can stay active in the nature for decades. Afterwards, as the drug therapy improved, fatal outcome of TB infection became rare. Now, we are hearing it again, because of the emergence of the drug resistant varities. I believe mycobacterial "sporulation" might explain not only the latent nature of the mycobacterial diseases, but also the bug's toughness to survive outside the host.

Elio's comment

An interesting point, Jaydip. As the story unfolds, this may become an important point to consider. Thanks for telling us.

[Mark O. Martin]

Hmmm. Many non Gram positives make "microspores" and I wonder if this kind of "cryptic" behavior is related? What a fine article!