Progenitor “Mycobacterium canettii” clone responsible for lymph node tuberculosis epidemic, Djibouti

Abstract

“Mycobacterium canettii,” an opportunistic human pathogen living in an unknown environmental reservoir, is the progenitor species from which Mycobacterium tuberculosis emerged. Since its discovery in 1969, most of the ≈70 known M. canettii strains were isolated in the Republic of Djibouti, frequently from expatriate children and adults. We show here, by whole-genome sequencing, that most strains collected from February 2010 through March 2013, and associated with 2 outbreaks of lymph node tuberculosis in children, belong to a unique epidemic clone within M. canettii. Evolution of this clone, which has been recovered regularly since 1983, may mimic the birth of M. tuberculosis. Thus, recognizing this organism and identifying its reservoir are clinically important.

Figure 1

Starburst genealogy within clone A of Mycobacterium canettii isolates, Djibouti, 2010–2013. The size of each branch, corresponding to the number of polymorphisms between 2 nodes, is indicated. The tree is based upon 55 polymorphisms, 18 of which are clustered in 1,660 base pairs. The relative position of Percy1129 is shown with (blue) or without (red) these 18 polymorphisms. The isolation year is indicated near each strain. The position of a hypothetical ancestor is indicated by the red. All cluster A strains are 2 up to a maximum of 5 polymorphisms away from this hypothetical ancestor after removal of the exceptional polymorphism cluster found in strain Percy1129. SNP, single-nucleotide polymorphism.

Figure 2

Early evolution of Mycobacterium tuberculosis was deciphered using clone A sequence data. A minimum spanning tree was drawn after removal of polymorphisms occurring in clusters, indicative of horizontal gene transfer events. The approximate position of the branching point of Percy302 (STB-K) the most distantly related M. canettii strain (5) is indicated by the blue star. The red star is the position of the most recent common ancestor of M. tuberculosis. The branch lengths of only the most internal branches are indicated. Branch length values inside clone A are <3. The position of the reference strain H37Rv is indicated. Four hundred seventy-one polymorphisms separate the red star from H37Rv. A logarithmic branch length representation was used.