# Bacterial metabolic remodeling by convergent evolution unlocks nutrient availability after a host switch

**Authors:** Amy C. Pickering, Jamie Gorzynski, Grace Taylor-Joyce, Rhodri Evans, Willow Fox, Pedro Melo, Joana Alves, Hannah Schlauch, Fiona Sargison, Gonzalo Yebra, Natalie Ring, J. Ross Fitzgerald

PMC · DOI: 10.1126/sciadv.adw9419 · Science Advances · 2026-02-06

## TL;DR

Staphylococcus aureus bacteria evolved to break down casein in cow's milk, allowing them to thrive in a new host environment.

## Contribution

The study reveals convergent evolution of protease overexpression in S. aureus to adapt to the bovine milk niche.

## Key findings

- Bovine S. aureus evolved protease-mediated casein degradation to access nutrients.
- Convergent evolution in different lineages led to overexpression of the protease aureolysin.
- Metabolic remodeling enables nutrient availability in the new host environment.

## Abstract

New pathogens typically arise from host jump events between species. Staphylococcus aureus is a multihost pathogen responsible for a global burden of human disease and a leading cause of intramammary infection in dairy cattle. Here, we demonstrate that following historical human-to-bovine host switch events, S. aureus has undergone adaptive metabolic remodeling in response to distinct nutrient availability in the dairy niche. In particular, we found that bovine S. aureus has evolved the capacity for protease-mediated degradation of casein, a protein abundant in bovine milk, to access nutrients for proliferation. This phenotype has evolved convergently in different S. aureus lineages via mutations in distinct gene loci driving overexpression of the protease aureolysin. Together, we have dissected a key host-adaptive trait, which facilitates the enzymatic release of nutrients from a substrate specific to the new host milieu. These findings highlight the remarkable evolutionary plasticity of a major bacterial pathogen underpinning its multihost species tropism.

Staphylococcus aureus has undergone metabolic remodeling to adapt to the dairy niche.

## Linked entities

- **Species:** Staphylococcus aureus (taxon 1280)

## Full-text entities

- **Genes:** CSN3 (casein kappa) [NCBI Gene 281728] {aka CSN10, CSN3K, CSNK}, CSN2 (casein beta) [NCBI Gene 281099]
- **Diseases:** bacterial infection (MESH:D001424), infection (MESH:D007239), mastitis (MESH:D008413), LOF (MESH:D006315), GOF (MESH:D015430), abscess infection (MESH:D000038)
- **Chemicals:** amino acids (MESH:D000596), anhydrotetracycline (MESH:C016229), ampicillin (MESH:D000667), SDS (MESH:D012967), zinc chloride (MESH:C016837), valine (MESH:D014633), galactose (MESH:D005690), BCAA (MESH:D000597), Zinc (MESH:D015032), purine (MESH:C030985), fructose (MESH:D005632), chloramphenicol (MESH:D002701), Arla Cravendale (-), carbohydrate (MESH:D002241), arginine (MESH:D001120), phosphate (MESH:D010710), Tween 20 (MESH:D011136), pyrimidine (MESH:C030986), calcium chloride (MESH:D002122), EDTA (MESH:D004492), ethanol (MESH:D000431), nucleotide (MESH:D009711), potassium chloride (MESH:D011189), sodium chloride (MESH:D012965), lactose (MESH:D007785), polyacrylamide (MESH:C016679)
- **Species:** Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Staphylococcus aureus RF122 (strain) [taxon 273036], Gallus gallus (bantam, species) [taxon 9031], Streptococcus agalactiae (species) [taxon 1311], Staphylococcus aureus (species) [taxon 1280], Escherichia coli (E. coli, species) [taxon 562], Bos taurus (bovine, species) [taxon 9913], Lactococcus lactis (species) [taxon 1358], Homo sapiens (human, species) [taxon 9606]
- **Mutations:** C at 180, serine-aspartate, (E) to (G)
- **Cell lines:** ED133 — Mus musculus (Mouse), Hybridoma (CVCL_M036), IM08B — Homo sapiens (Human), Melanoma, Cancer cell line (CVCL_C6NJ)

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12880543/full.md

## References

65 references — full list in the complete paper: https://tomesphere.com/paper/PMC12880543/full.md

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Source: https://tomesphere.com/paper/PMC12880543