Portrait of a generalist bacterium: pathoadaptation, metabolic specialization and extreme environments shape diversity of .

Unlabelled: is a Gram-positive, coagulase-negative staphylococcus found in diverse environments including soil and freshwater, meat, and dairy foods. is also an important cause of urinary tract infections (UTIs) in humans, and mastitis in cattle. However, the genetic determinants of virulence have not yet been identified, and it remains unclear whether there are distinct sub-populations adapted to human and animal hosts. Using a diverse sample of isolates from food, animals, environmental sources, and human infections, we characterized the population structure and diversity of global populations of . We found that divergence of the two major clades of is likely facilitated by barriers to horizontal gene transfer (HGT) and differences in metabolism. Using genome-wide association study (GWAS) tools we identified the first Type VII secretion system (T7SS) described in and its association with bovine mastitis. Finally, we found that in general, strains of from different niches are genetically similar with the exception of built environments, which function as a 'sink' for populations. This work increases our understanding of the ecology of and of the genomics of bacterial generalists.

Data Summary: Raw sequencing data for newly sequenced isolates have been deposited to the NCBI SRA under the project accession PRJNA928770. A list of all genomes used in this work and their associated metadata are available in the supplementary material. Custom scripts used in the comparative genomics and GWAS analyses are available here: https://github.com/myoungblom/sapro_genomics .

Impact Statement: It is not known whether human and cattle diseases caused by represent spillover events from a generalist adapted to survive in a range of environments, or whether the capacity to cause disease represents a specific adaptation. Seasonal cycles of UTIs and molecular epidemiological evidence suggest that these infections may be environmentally-acquired rather than via transmission from person to person. Using comparative genomics and genome wide association study tools, we found that appears adapted to inhabit a wide range of environments (generalist), with isolates from animals, food, natural environments and human infections being closely related. Bacteria that routinely switch environments, particularly between humans and animals, are of particular concern when it comes to the spread of antibiotic resistance from farm environments into human populations. This work provides a framework for comparative genomic analyses of bacterial generalists and furthers our understanding of how bacterial populations move between humans, animals, and the environment.