My­cobac­te­ria Make Spores?

by Pe­ter Set­low

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

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 My­co­bacterium 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.