Transcriptomic and genomic evidence for Streptococcus agalactiae adaptation to the bovine environment.

Background: Streptococcus agalactiae is a major cause of bovine mastitis, which is the dominant health disorder affecting milk production within the dairy industry and is responsible for substantial financial losses to the industry worldwide. However, there is considerable evidence for host adaptation (ecotypes) within S. agalactiae, with both bovine and human sourced isolates showing a high degree of distinctiveness, suggesting differing ability to cause mastitis. Here, we (i) generate RNAseq data from three S. agalactiae isolates (two putative bovine adapted and one human) and (ii) compare publicly available whole genome shotgun sequence data from an additional 202 isolates, obtained from six host species, to elucidate possible genetic factors/adaptations likely important for S. agalactiae growth and survival in the bovine mammary gland.

Results: Tests for differential expression showed distinct expression profiles for the three isolates when grown in bovine milk. A key finding for the two putatively bovine adapted isolates was the up regulation of a lactose metabolism operon (Lac.2) that was strongly correlated with the bovine environment (all 36 bovine sourced isolates on GenBank possessed the operon, in contrast to only 8/151 human sourced isolates). Multi locus sequence typing of all genome sequences and phylogenetic analysis using conserved operon genes from 44 S. agalactiae isolates and 16 additional Streptococcus species provided strong evidence for acquisition of the operon via multiple lateral gene transfer events, with all Streptococcus species known to be major causes of mastitis, identified as possible donors. Furthermore, lactose fermentation tests were only positive for isolates possessing Lac.2. Combined, these findings suggest that lactose metabolism is likely an important adaptation to the bovine environment. Additional up regulation in the bovine adapted isolates included genes involved in copper homeostasis, metabolism of purine, pyrimidine, glycerol and glucose, and possibly aminoglycoside antibiotic resistance.

Conclusion: We detected several genetic factors likely important in S. agalactiae's adaptation to the bovine environment, in particular lactose metabolism. Of concern is the up regulation of a putative antibiotic resistance gene (GCN5-related N-acetyltransferase) that might reflect an adaptation to the use of aminoglycoside antibiotics within this environment.