Researchers from the University of Warsaw and the Spanish National Research Council show that adhesion by Staphylococcus aureus shapes the course of bacteremia and may help predict patient risk.

Staphylococcus aureus is one of the leading causes of severe bloodstream infections. Although this bacterium is widely associated with high virulence and treatment challenges, the clinical course of infection varies greatly between patients. In some cases, the infection is controlled; in others, it progresses to sepsis, organ complications or death. A new study to be published in Nature Communications shows that this variation may depend not only on the presence of individual virulence genes, but also on the balance between two bacterial traits: the ability to adhere to host proteins and the ability to produce toxins.

The team, led by dr. Marta Zapotoczna from the Laboratory of Infection Biology at the Biological and Chemical Research Centre, University of Warsaw, and dr Francesc Coll and the Spanish National Research Council, analysed 236 S. aureus isolates collected from patients with bacteremia and their infecting isolate(s). The researchers measured how strongly individual bacterial strains bound human fibrinogen and fibronectin, which are host proteins that play important roles during infection, and then integrated these data with whole-genome sequencing and clinical information from the patients.

The results were unexpected. Strains that bound fibrinogen more strongly were associated with a stronger inflammatory response, measured in part by C-reactive protein levels. At the same time, particularly when these strains did not produce active α-toxin, they were associated with lower mortality. In other words, under certain conditions, “stickier” bacteria may more effectively alert the immune system and help the host contain the infection.

“Our results show that, in S. aureus bacteremia, adhesion is not simply a trait that helps bacteria cause infection. In a specific context, it may trigger an inflammatory response that helps the body control the infection,” say the authors.

The researchers describe this phenomenon as a virulence trade-off. Strains with high adhesion and low toxicity more often induced a strong, but potentially beneficial, inflammatory response. By contrast, weakly adhesive strains that produced α-toxin may have been better able to evade host defence mechanisms and were more often associated with more severe disease.

Genomic analyses also identified genetic determinants of adhesion. These included gene variants encoding known adhesins, such as clfA, fnbA and fnbB, as well as genes involved in bacterial cell wall organisation and metabolism, including spa, csbB and glcA. Follow up mechanistic experiments showed that protein A can limit ClfA-dependent adhesion to fibrinogen, most likely by sterically blocking the binding site. CsbB, in turn, affects the exposure of ClfA on the bacterial surface, while GlcA links bacterial metabolism with adhesion to fibronectin.

The importance of the study extends beyond a basic understanding of S. aureus biology. The authors suggest that, in the future, simultaneous profiling of adhesive and toxic properties of clinical isolates could help assess risk in patients with bacteremia. This direction of research may support the development of more precise diagnostic tools and better-tailored treatment strategies. Further work in this area is also being pursued in new projects led by dr Marta Zapotoczna, including a SONATA BIS project recently funded by the National Science Centre in Poland.

“Our work shows that, to understand the pathogenic potential of bacteria, we need to study not only their antibiotic resistance, but also the mechanisms by which pathogens interact with the patient’s body. Focusing on mechanisms of pathogenicity may bring us closer to predicting and controlling infection-related risk, while complementing classical approaches based on the analysis of antibiotic resistance genes,” adds dr. Zapotoczna.

The article is the result of a collaboration between researchers from Poland, Spain, the United Kingdom and France. The study involved scientists from the University of Warsaw, the Medical University of Warsaw, Jagiellonian University Medical College, the University of Birmingham, the Spanish National Research Council, and French research and clinical centres affiliated with INSERM, CNRS, the University of Lyon and the National Reference Centre for Staphylococci.