Abstract
BackgroundMycobacterium avium (M. avium) subspecies vary widely in both pathogenicity and host specificity, but the genetic features contributing to this diversity remain unclear.ResultsA comparative genomic approach was used to identify large sequence polymorphisms among M. avium subspecies obtained from a variety of host animals. DNA microarrays were used as a platform for comparing mycobacterial isolates with the sequenced bovine isolate M. avium subsp. paratuberculosis (MAP) K-10. Open reading frames (ORFs) were classified as present or divergent based on the relative fluorescent intensities of the experimental samples compared to MAP K-10 DNA. Multiple large polymorphic regions were found in the genomes of MAP isolates obtained from sheep. One of these clusters encodes glycopeptidolipid biosynthesis enzymes which have not previously been identified in MAP. M. avium subsp. silvaticum isolates were observed to have a hybridization profile very similar to yet distinguishable from M. avium subsp. avium. Isolates obtained from cattle (n = 5), birds (n = 4), goats (n = 3), bison (n = 3), and humans (n = 9) were indistinguishable from cattle isolate MAP K-10.ConclusionGenome diversity in M. avium subspecies appears to be mediated by large sequence polymorphisms that are commonly associated with mobile genetic elements. Subspecies and host adapted isolates of M. avium were distinguishable by the presence or absence of specific polymorphisms.
Highlights
Mycobacterium avium (M. avium) subspecies vary widely in both pathogenicity and host specificity, but the genetic features contributing to this diversity remain unclear
Marsh and coworkers have described the presence of several large sequence polymorphisms among sheep and cattle isolates of M. avium subspecies paratuberculosis (MAP) [5,6], while Semret et al have reported on the presence of polymorphic regions that are shared between M. avium subspecies avium (MAA) and MAP sheep isolates [7]
Validation of microarray sensitivity and specificity The reference isolate MAP K-10 was compared to the sequenced M. avium subspecies hominissuis (MAH) isolate 104 in order to evaluate the performance of the oligonucleotide microarray as a platform for comparative genomic hybridizations
Summary
Mycobacterium avium (M. avium) subspecies vary widely in both pathogenicity and host specificity, but the genetic features contributing to this diversity remain unclear. BMC Genomics 2008, 9:135 http://www.biomedcentral.com/1471-2164/9/135 genetics of MAP It remains unclear what MAP virulence factors are important for both infection and persistence, and despite observed phenotypic and genetic differences between MAP isolates obtained from sheep and cattle, the biological basis for host specificity remains unclear. Previous work in our laboratory has utilized DNA microarrays to compare the genome content of members of the M. avium complex (MAC) which includes MAP, M. avium subspecies avium (MAA), M. avium subspecies silvaticum (MAS), M. avium subspecies hominissuis (MAH) and M. intracellulare [4]. These findings revealed that non-MAP MAC isolates do not contain several large regions of genomic DNA that are present in MAP K-10. The biological consequence of these large sequence polymorphisms has not yet been determined
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