Comparative Whole-Genome Hybridization Reveals Genomic Islands inBrucellaSpecies

Abstract

ABSTRACTBrucellaspecies are responsible for brucellosis, a worldwide zoonotic disease causing abortion in domestic animals and Malta fever in humans. Based on host preference, the genus is divided into six species.Brucella abortus,B. melitensis, andB. suisare pathogenic to humans, whereasB. ovisandB. neotomaeare nonpathogenic to humans andB. canishuman infections are rare. Limited genome diversity exists amongBrucellaspecies. Comparison ofBrucellaspecies whole genomes is, therefore, likely to identify factors responsible for differences in host preference and virulence restriction. To facilitate such studies, we used the complete genome sequence ofB. melitensis16M, the species highly pathogenic to humans, to construct a genomic microarray. Hybridization of labeled genomic DNA fromBrucellaspecies to this microarray revealed a total of 217 open reading frames (ORFs) altered in fiveBrucellaspecies analyzed. These ORFs are often found in clusters (islands) in the 16M genome. Examination of the genomic context of these islands suggests that many are horizontally acquired. Deletions of genetic content identified inBrucellaspecies are conserved in multiple strains of the same species, and genomic islands missing in a given species are often restricted to that particular species. These findings suggest that, whereas the loss or gain of genetic material may be related to the host range and virulence restriction of certainBrucellaspecies for humans, independent mechanisms involving gene inactivation or altered expression of virulence determinants may also contribute to these differences.