Abstract
BackgroundThe rapid identification of lineage remains a challenge in the genotyping of clinical isolates of recombinogenic pathogens. The chromosome of Mycobacterium avium subsp. hominissuis (MAH), an agent of Mycobacterium avium complex (MAC) lung disease, is often mosaic and is composed of chromosomal segments originating from different lineages. This makes it difficult to infer the MAH lineage in a simple experimental set-up. To overcome this difficulty, we sought to identify chromosomal marker genes containing lineage-specific alleles by genome data mining.ResultsWe conducted genetic population structure analysis, phylogenetic analysis, and a survey of historical recombination using data from 125 global MAH isolates. Six MAH lineages (EA1, EA2, SC1, SC2, SC3, and SC4) were identified in the current dataset. One P-450 gene (locus_tag MAH_0788/MAV_0940) in the recombination-cold region was found to have multiple alleles that could discriminate five lineages. By combining the information about allele type from one additional gene, the six MAH lineages as well as other M. avium subspecies were distinguishable. A recombination-cold region of 116 kb contains an insertion hotspot and is flanked by a mammalian cell-entry protein operon where allelic variants have previously been reported to occur. Hence, we speculate that the acquisition of lineage- or strain-specific insertions has introduced homology breaks in the chromosome, thereby reducing the chance of interlineage recombination.ConclusionsThe allele types of the newly identified marker genes can be used to predict major lineages of M. avium. The single nucleotide polymorphism typing approach targeting multiallelic loci in recombination-cold regions will facilitate the epidemiological study of MAC, and may also be useful for equivalent studies of other nontuberculous mycobacteria potentially carrying mosaic genomes.
Highlights
The rapid identification of lineage remains a challenge in the genotyping of clinical isolates of recombinogenic pathogens
We previously revealed the presence of multiple Mycobacterium avium subsp. hominissuis (MAH) lineages within a single country, most notably Japan, and the occurrence of extensive interlineage recombination on the chromosome [21]
Detection of M. avium lineages MAH lineages in the global population were inferred using 48,972 filtered polymorphic sites detected in 125 genomes, which have been available in the PATRIC database [29] since February 2018 (Additional file 1)
Summary
The rapid identification of lineage remains a challenge in the genotyping of clinical isolates of recombinogenic pathogens. Hominissuis (MAH), an agent of Mycobacterium avium complex (MAC) lung disease, is often mosaic and is composed of chromosomal segments originating from different lineages. This makes it difficult to infer the MAH lineage in a simple experimental set-up. Insertion sequence fingerprinting is another representative approach [16, 18, 19] Because both techniques assess the fragment length of highly variable loci with reversible repeat numbers, the dissimilarity of fragment length patterns may not reflect the relatedness of the remaining genome, which gradually diversifies, accumulating mutations and recombinations, during the long-term evolution of the species. The single nucleotide polymorphism (SNP)-based approach [20] is better suited for lineage inference
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