Massive genome decay and insertion sequence expansion drive the evolution of a novel host-restricted bacterial pathogen

Abstract

Background: The emergence of new bacterial pathogens represents a major threat to public and veterinary health. Staphylococcus aureus is a multi-host bacterial species comprising pathogenic clones with distinct tropisms for human and livestock species. A S. aureus microaerophilic subspecies, Staphylococcus aureus subsp. anaerobius, is responsible for outbreaks of a specific lymphadenitis pathology (Morel's disease) exclusively found in small ruminants. However, the evolutionary history of S.aureus subsp. anaerobius and its genetic relatedness to S.aureus are unknown. Results: Evolutionary genomic analyses of clinical S.aureus subsp. anaerobius isolates sampled across 3 decades revealed this clone emerged from a S.aureus progenitor about 1000 years ago (95%CI: 716-1184), before differentiating into two distinct lineages representing African (emerged in 1930 [1907-1951)) and European (1777 [1716-1832]) isolates. S.aureus subsp. anaerobius has undergone limited clonal expansion, with a restricted population size, and an evolutionary rate 10-fold slower than S. aureus. The transition to a highly niche-specific pathogen of small ruminant lymph nodes involved acquisition of a pathogenicity island encoding an effector with ruminant host-specificity, large genomic rearrangements, and the accumulation of at least 205 pseudogenes resulting in a highly fastidious metabolism underpinning its restricted ecological niche. Importantly, acquisition and expansion of ~87 insertion sequences located in conserved intergenic regions provided distinct mechanisms for the control of expression of flanking genes, representing a novel concept of transcriptional regulon. Conclusions: Our findings provide a remarkable example of the evolutionary trajectory of a host-restricted bacterial pathogen that resulted from extensive remodeling of the S. aureus genome.

Genetic Diversity in Staphylococcus aureus and Its Relation to Biofilm Production

“…They are responsible for the recombination and stabilization of some genes which are responsible for resistance, though they do not code for resistance. These IS sequences are responsible for inducing changes in the expression levels of chromosomal genes and thus are very important in the process of evolution of the bacterial genome [41]. IS sequences can affect the transcription of other genes which are nearby, either by direct insertion or by polar effect, in order to inactivate them.…”