Mycobacterium microti: More diverse than previously thought

Abstract

Mycobacterium microti is a member of the Mycobacterium tuberculosis complex of bacteria. This species was originally identified as a pathogen of small rodents and shrews and was associated with limited diversity and a much reduced spoligotype pattern. More recently, specific deletions of chromosomal DNA have been shown to define this group of organisms, which can be identified by the absence of chromosomal region RD1(mic). We describe here the molecular characteristics of 141 strains of the Mycobacterium tuberculosis complex isolated in Great Britain over a 14-year period. All strains have characteristic loss of some spoligotype spacers and characteristic alleles at the ETR-E and ETR-F variable-number tandem-repeat (VNTR) loci, and a sample of these strains was deleted for regions RD7, RD9, and RD1(mic) but intact for regions RD4 and RD12. We therefore identified these strains as M. microti and show that they have much more diverse spoligotype patterns and VNTR types than previously thought. The most common source of these strains was domestic cats, and we show that the molecular types of M. microti are geographically localized in the same way that molecular types of Mycobacterium bovis are geographically localized in cattle in the United Kingdom. We describe the pathology of M. microti infection in cats and suggest that the feline disease is a spillover from a disease maintained in an unknown wild mammal, probably field voles. The location of the cats with M. microti infection suggests that they do not overlap geographically with the strains of Mycobacterium bovis in Great Britain.

FIG. 1.

Sample of M. microti spoligotype patterns identified between 1994 and October 2008. VLA names for the spoligotype pattern, the international names for spoligotype patterns assigned by www.Mbovis.org, and the spoligotype patterns are shown. Control strains of M. pinnipedii (SB0659, [7]) and M. tuberculosis (H37Rv) are included. We also isolated strains with spoligotype patterns SB0988, SB1505, SB1507, SB1510, and SB1512.

FIG. 2.

Geographical localization of the common M. microti genotypes of all hosts and the common M. bovis genotypes of cats. (A) Locations of the common genotypes (more than a single isolate) of M. microti. Four spoligotypes are shown as well as strains with spoligotype SB0112 (VLA type 19) which have been divided into genotypes (19:a to 19:e), using a combination of spoligotype and VNTR type. (B) Locations of M. bovis genotypes (spoligotype plus VNTR type), with more than a single isolate, from cats.

FIG. 3.

Location of cats with M. bovis infection (black circles) (n = 43), cats with M. microti infection (red circles) (n = 67), captured voles with M. microti infection (red squares) (5, 43), and 1- (yellow) and 2-year (gray) testing parishes for bovine tuberculosis in cattle (last quarter of 2008). Two cats, one with M. microti infection and one with M. bovis infection, are located in unexpected areas, possibly as the result of their owners relocating.