Staphylococcus aureus (S. aureus) is a common type of bacterium that is usually harmless to many people, but for others can cause potentially life-threatening infections. Now, a new study gives a detailed understanding of how these bacteria adapt and evolve to survive on and in their human carriers at a genetic level. The findings could help improve the prevention, diagnosis, and treatment of certain infections.
The study, “The mutational landscape of Staphylococcus aureus during colonization,” is published in Nature Communications and led by researchers at Wellcome Sanger Institute, the University of Cambridge, the Institute of Biomedicine of Valencia (IBV) at the Spanish National Research Council (CSIC), and their collaborators.
The international team analyzed the genomes of more than 7,000 S. aureus samples obtained from more than 1,500 human carriers to identify genetic changes that originated in the bacteria while it was in its natural environment. Through computational analysis, they were able to identify the recurrent genetic changes in the bacteria that could have contributed to survival during human colonization.
This new study is the first time researchers have carried out a large-scale genetic analysis of S. aureus from samples of human carriers, instead of observing the bacteria in a laboratory setting.
The researchers identified changes in genes associated with nitrogen metabolism, suggesting that this is a key metabolic process necessary for the colonization of humans by S. aureus. They also identified mutations in genes that could influence the way the bacteria interact with human cells and the immune system.
The researchers also suggested that these bacterial strains might use factors secreted by other bacterial strains to colonize humans without producing these themselves—something they call “cheater” cells.
Additionally, this study confirmed that S. aureus acquires resistance mutations to antibiotics such as fusidic acid, mupirocin, and trimethoprim.
Further research is needed to fully understand the role these bacteria play in human colonization, and if there is a way to target these pathways in the future to help prevent, diagnose, or treat infections caused by S. aureus.
Overall, this new research reveals key biological processes that S. aureus employs to survive in humans.
Francesc Coll, PhD, 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, as well as 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.”
Ewan Harrison, PhD, 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 in order to survive on and in their human carriers at a genetic level. Through our new analysis, we were able to study these strains in their natural habitat; highlighting previously unknown mutations that give certain Staphylococcus aureus strains the upper hand. We hope that further investigation of the pathways we have uncovered will help improve the prevention, diagnosis, and treatment of infections caused by these bacteria.”
