Researchers have elucidated how the bacterium Staphylococcus aureus genetically evolves to adapt to humans, including mutations that enable certain strains to dodge the immune system and gain antibiotic resistance.
The most comprehensive study to date on how a common bacterium, Staphylococcus aureus, adapts to exist on the human body could enhance methods for preventing, diagnosing, and treating specific infections.
This research, conducted by the Wellcome Sanger Institute, the University of Cambridge, and the Institute of Biomedicine of Valencia (IBV) at the Spanish National Research Council (CSIC), involved analyzing the genomes of thousands of S. aureus samples collected from human noses and skin to pinpoint genes crucial for the bacteria’s survival and adaptation.
Published today (13 January) in Nature Communications, the study employed a novel method to examine the genomes of bacteria from human carriers, revealing specific adaptations of these bacteria in their natural environment. This insight uncovered essential mutations that help certain strains evade human immune defenses and develop resistance to antibiotics.
This extensive genetic analysis shed light on several previously unidentified genes and biological pathways involved in the colonization of S. aureus.
More research is needed to fully comprehend the significance of these pathways in human colonization and explore potential ways to target them in the future for preventing, diagnosing, or treating S. aureus infections.
Bacteria are often present on or within the body without causing harm, a phenomenon known as colonization. One example is S. aureus, which can be found in the noses of up to 30% of the world’s population, as well as on the skin and in the intestines1.
However, in individuals with weakened immune systems, S. aureus can enter the bloodstream and lead to infections, ranging from mild skin and soft tissue issues to more severe conditions like sepsis and pneumonia1.
This groundbreaking study marks the first extensive genetic analysis of S. aureus from samples taken from human carriers, moving beyond laboratory observations.
The international team evaluated the genomes of over 7,000 S. aureus samples derived from more than 1,500 human carriers to uncover genetic variations that occurred while the bacteria thrived in their natural setting. Through computational methods, they identified recurrent genetic alterations in the bacteria that may have aided their survival during human colonization.
The researchers discovered changes in genes related to nitrogen metabolism, indicating that this metabolic process is vital for S. aureus colonization in humans. They also found mutations in genes that could affect how the bacteria interact with human cells and the immune system.
Some strains of S. aureus possess mutations in genes regulating the mechanisms the bacteria utilize to evade the human immune system, possibly pointing to an immune evasion strategy. Researchers propose that these bacterial strains may rely on factors secreted by other strains to successfully colonize humans — a phenomenon they term “cheater” cells.
Moreover, the study verified that S. aureus develops resistance mutations to antibiotics such as fusidic acid, mupirocin, and trimethoprim.
In summary, this research uncovers essential biological processes that S. aureus employs to thrive within humans. Understanding the evolution and genetic adaptation of bacteria in their natural contexts — including asymptomatic colonization or during infection — is crucial for enhancing prevention, diagnosis, and treatment of diseases.
Dr. Francesc Coll, the lead author from the Institute of Biomedicine of Valencia at CSIC, stated: “Grasping how bacteria react to antibiotic treatment has enabled the identification of genetic changes that permit their survival against antibiotic attacks. These mutations can serve as diagnostic indicators and aid in developing new therapeutic strategies, facilitating a more effective and rational use of antibiotics. Studies of bacterial adaptation like this could unveil immune evasion mechanisms — clarifying how bacteria adapt to escape detection and attack by our immune systems. This knowledge could support the identification of new antigens, components of bacteria that the immune system sees as foreign or harmful, leading to the design of new vaccines.”
Dr. Ewan Harrison, senior author from the Wellcome Sanger Institute, remarked: “While Staphylococcus aureus bacteria are benign for many, they pose severe risks of infection for others. Our study provides fresh insights into the genetic adaptations of these bacteria, allowing them to survive on or in human carriers. By analyzing these strains in their natural habitat, we have highlighted previously unknown mutations that can give certain Staphylococcus aureus strains a competitive advantage. We hope that further exploration of these pathways will enhance methods for preventing, diagnosing, and treating infections caused by these bacteria.”
