Highly Reduced Genome of the New Species Mycobacterium uberis, the Causative Agent of Nodular Thelitis and Tuberculoid Scrotitis in Livestock and a Close Relative of the Leprosy Bacilli

Abstract

Nodular thelitis is a chronic enzootic infection affecting dairy cows and goats. The causative agent was recently shown to be related to the leprosy-causing bacilli Mycobacterium leprae and Mycobacterium lepromatosis In this study, the genome of this pathogen was sequenced and analyzed. Phylogenomic analyses confirmed that the pathogen present in nodular thelitis and tuberculoid scrotitis is a distinct species related to the leprosy bacilli and Mycobacterium haemophilum Because the pathogen was originally isolated from a bovine udder, it was named "Mycobacterium uberis" The genome of "M. uberis" is only 3.12 Mb in length, which represents the smallest mycobacterial genome identified so far but which is close to that of leprosy bacilli in size. The genome contains 1,759 protein-coding genes and 1,081 pseudogenes, indicative of extensive reductive evolution and likely the reason that M. uberis cannot be grown axenically. The pseudogenization and genome reduction in M. uberis seem to have been to some extent independent from the results determined for the genomes of the leprosy bacilli.IMPORTANCEM. uberis is an emerging skin pathogen in dairy animals. Its genome underwent massive reduction and gene decay, leading to a minimal set of genes required for an obligatory intracellular lifestyle, which highly resembles the evolution of the leprosy agents M. leprae and M. lepromatosis The genomic similarity between M. uberis and the leprosy bacilli can help in identifying key virulence factors of these closely related species or in identifying genes responsible for the distinct differences between thelitis or scrotitis and leprosy with respect to clinical manifestations. Specific DNA markers can now be developed for quick detection of this pathogen.

Keywords: Mycobacterium uberis; evolutionary biology; genome analysis; granulomatous dermatitis; veterinary pathogens.

FIG 1

Phylogenetic tree of Mycobacterium uberis and selected mycobacterial species. The tree was created in MEGA7 from concatenated amino acid sequences (3,696 positions) of 10 proteins (DnaN, RplI, GrpE, MetG, RplY, PheT, FtsQ, HolA, MiaA, and FtsY) (18) and inferred by using the maximum likelihood method based on the JTT matrix-based model. The tree is drawn to scale, with branch lengths measured at the number of substitutions per site. Bootstrap support values, estimated from 500 replicates, are given below each branch. Mycobacteroides abscessus (previously Mycobacterium abscessus) was used as the outgroup.