Staphylococcus aureus, a key human pathogen and a common inhabitant of the nose and skin evolves mainly to survive and persist during colonization.
The study, by the Wellcome Sanger Institute, the University of Cambridge, the Institute of Biomedicine of Valencia (IBV) at the Spanish National Research Council (CSIC), and their collaborators, is the most detailed study to date on how Staphylococcus aureus adapts to living on the human body. It could enhance the prevention, diagnosis, and treatment of some infections.
The team used the genomes of thousands of S. aureus isolates cultured from the human nose and on the skin. They investigated which genes are essential for the bacteria to adapt and persist.
Using a new approach to analyze the genomes of bacteria from human carriers, researchers highlighted precisely how these bacteria adapt in their natural habitat.
The study revealed key mutations that allow some strains of S. aureus to evade the immune system and resist antibiotics. The large-scale genetic analysis also found new genes and pathways involved in S. aureus colonization. Further research is needed to fully understand these roles and find ways to target them to prevent, diagnose, or treat S. aureus infections.
Bacteria often live on or in the body without causing harm, a process known as colonization. S. aureus is a bacterium found in the nose of up to 30% of the population, on the skin, or in the intestine.
In individuals with weakened immune systems, S. aureus can enter the bloodstream, causing infections that range from mild skin infections to severe conditions like sepsis and pneumonia.
In this study, researchers conducted a large-scale genetic analysis of S. aureus from human carriers rather than lab samples for the first time. The international team analyzed the genomes of over 7,000 S. aureus samples from more than 1,500 human carriers to identify genetic changes occurring naturally in the bacteria. Through computational analysis, they identified recurring genetic changes that help the bacteria survive during human colonization.
Researchers found gene changes related to nitrogen metabolism, suggesting that S. aureus must colonize humans to do so. They also identified mutations affecting how the bacteria interact with human cells and the immune system.
Some S. aureus strains have mutations to evade the immune system, highlighting an evasion strategy. They might even use factors secreted by other strains to colonize humans without making them—’cheater’ cells. This study also confirmed that S. aureus acquires resistance mutations to antibiotics like fusidic acid, mupirocin, and trimethoprim.
This new research uncovers key biological processes that S. aureus uses to survive in humans. We can improve disease prevention, diagnosis, and treatment by studying how bacteria evolve and adapt to their natural environment, whether during symptom-free colonization or infections.
Dr Francesc Coll, first author from the Institute of Biomedicine of Valencia at the Spanish National Research Council (CSIC), said: “Understanding how bacteria respond to antibiotic treatments has made it possible to identify the genetic changes that allow them to survive the attack of antibiotics. These mutations can be used as diagnostic markers to design new therapeutic strategies and a more rational and effective use of antibiotics.”
“Studies of bacterial adaptation like this could also reveal mechanisms of immune evasion – how bacteria adapt to evade recognition and attack by our immune system. This could help identify new antigens, components of the bacteria that the immune system recognizes as foreign or dangerous, and design new vaccines.”
Dr Ewan Harrison, senior author from the Wellcome Sanger Institute, said: “While Staphylococcus aureus bacteria are harmless to many people, for others, they can cause potentially life-threatening infections. Our study gives a detailed new understanding of how these bacteria adapt and evolve to survive on and in their human carriers at a genetic level.”
“Through our new analysis, we could study these strains in their natural habitat, highlighting previously unknown mutations that give certain Staphylococcus aureus strains the upper hand. Further investigation of our uncovered pathways will help improve the prevention, diagnosis, and treatment of infections caused by these bacteria.”
Journal Reference:
- Coll, F., Blane, B., Bellis, K.L. et al. The mutational landscape of Staphylococcus aureus during colonization. Nat Commun 16, 302 (2025). DOI: 10.1038/s41467-024-55186-x
