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The recombination-cold region as an epidemiological marker of recombinogenic opportunistic pathogen Mycobacterium avium.

ABSTRACT: BACKGROUND:The 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. RESULTS:We 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. CONCLUSIONS:The 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.

SUBMITTER: Yano H

PROVIDER: S-EPMC6798384 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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The recombination-cold region as an epidemiological marker of recombinogenic opportunistic pathogen Mycobacterium avium.

Yano Hirokazu H Suzuki Haruo H Maruyama Fumito F Iwamoto Tomotada T

BMC genomics 20191017 1

<h4>Background</h4>The 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 chromos ...[more]

PMID: 31623552

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Project description:Mycobacterium avium subspecies paratuberculosis (MAP) infection is established following the ingestion of bacteria, their penetration of the intestinal mucosa and subsequent events of the host-parasite interaction. These bacteria invade M cells, macrophages and are capable of resisting host defenses and multiply to reach very high numbers intracellular. Mycobactrium avium subsp. avium (MAA) is an antigenically and genetically similar organisms but is relatively nonpathogenic for cattle. MAA organisms appear to infect cattle, but unlike cattle infected with MAP, cattle infected with MAA typically mount an effective systemic immune response, form caseous granuloma, and eliminate the infection. This study was designed to understand the similarities and differences in the host responses during MAP and MAA infection. Neonatal calves were infected (ligated ileal loops) with PBS, MAP, or avirulent MAA following which samples were collected at 30 min, 1h, 2h, 4h, 8h, or 12h. Post-infection, RNA was collected, processed, and then hybridized to custom bovine gene expression arrays, each of which represented 13,258 transcripts spotted in duplicate. Arrays were normalized by scaling against the average reference intensity value (i.e., average across all arrays), normalized by global mean, and then log transformed before statistical analyses were performed. Pairwise comparisons of averaged signal values and Student’s t test were performed using GeneSifter software (VizX Labs, Seattle, WA). A fold-change of at least 1.5-fold and a p value of 0.05 or less was required for a difference in signal to be considered statistically significant. When comparing the transcriptional responses of calves infected with the MAA versus MAP, unique patterns of expression were clearly visible. In general, numbers of transcripts altered in response to infection were much greater for MAA-infected animals than for those infected with the MAP. No genes were significantly up-regulated in MAP-infected animals at the earliest time point tested (30 min), and only modest numbers of genes were increased in expression over the experimental time course. On the other hand, up-regulated transcripts were detected by 30 min in MAA-infected animals and peaked by 2 hr. Differences in the numbers of down-regulated genes between MAP-infected and MAA-infected animals (compared to PBS-infected controls) were less pronounced. At the earliest time points, MAP-infected calves had a greater number of down-regulated genes than did animals infected with MAA. This trend was reversed at 8 and 12 hr post-infection. Keywords: Gene expression profiling by microarray

Dataset Information

The recombination-cold region as an epidemiological marker of recombinogenic opportunistic pathogen Mycobacterium avium.

Publications

The recombination-cold region as an epidemiological marker of recombinogenic opportunistic pathogen Mycobacterium avium.

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