In infectious disease research, it is widely accepted that disrupting bacterial communication signals is beneficial. But this is not always the case, reveals a study from UNIGE and NTU Singapore.
Is blocking the bacterial communication system always beneficial? A team from the University of Geneva (UNIGE) and the Nanyang Technological University (NTU Singapore) is challenging this widely held idea in infectious disease research. By studying a bacterium responsible for a severe heart infection, the scientists show that disrupting bacterial communication signals can be associated with unfavorable clinical outcomes for patients.
Scanning electron microscope image of the bacterium Enterococcus faecalis in a biofilm. A pseudo-green coloration was applied with Gemini AI to the original image for visualization purposes only.
© Haris Antypas, Kenneth Ng Kok Fei Published in
Nature Communications, these findings pave the way for more targeted and potentially more effective therapeutic strategies against this type of infection.
Infective endocarditis is a serious infection of the inner lining of the heart, most often the heart valves. It can be caused by different bacteria, including
Enterococcus faecalis, which is particularly widespread. These bacteria often coordinate their collective behaviors through a process called
quorum sensing, a chemical communication system that allows them to assess the number of bacteria present nearby. Through this system, they organize into dense clusters, called biofilms, which disrupt valve function and resist antibiotics. Infective endocarditis is thus associated with high morbidity.
A team from SCELSE - the Singapore Centre for Environmental Life Sciences and Engineering at NTU, a multidisciplinary research centre on biofilms and the microbiome, and from the Faculty of Medicine at UNIGE is now challenging the idea - widespread in infectious disease research - that blocking this communication system is always beneficial. While
quorum sensing inhibitors are actively being studied as anti-virulence therapies, this study shows that suppressing bacterial signaling in heart infections can, on the contrary, prove counterproductive by promoting a more aggressive disease.
The scientists indeed found that when
Enterococcus faecalis loses its ability to communicate with neighboring bacteria, it forms larger and more resistant biofilms on heart valves, leading to more severe clinical outcomes.
These findings challenge a popular idea in infectious disease research that blocking
quorum sensing is always beneficial.
Blood flow silences bacterial communication
By combining devices that mimic blood flow and an animal model of heart infection, the team discovered that in the early stages of infection, blood flow actively suppresses
quorum sensing. "On the surface of heart valves, bacteria are exposed to intense blood flow," explains Dr. Haris Antypas, senior research fellow at SCELSE, lead author and co-corresponding author of the study. "This flow washes away the chemical signals used by bacteria to communicate, thus keeping
quorum sensing switched off."
As the infection progresses, bacteria burrow deeper into the valvular vegetations, where they are protected from blood flow. At this stage, the scientists observed that
quorum sensing activates and plays a braking role, limiting excessive biofilm growth. Strikingly, bacteria completely lacking
quorum sensing bypass this control mechanism. In animal models, these deficient strains formed larger biofilms, showed increased tolerance to antibiotics, and caused more severe disease.
The team attributed this effect to two key mechanisms: reduced production of bacterial proteases - enzymes that degrade proteins - and metabolic reprogramming that allows bacteria to use available host nutrients more efficiently, fueling persistent growth.
More unfavorable outcomes in affected individuals
The study also analyzed
E. faecalis bacteria isolated from patients with infective endocarditis in the United States and Switzerland. Nearly half of the clinical isolates lacked
quorum sensing. These cases were associated with prolonged presence of bacteria in the bloodstream despite active antibiotic treatment. "These are not rare mutants," emphasizes Dr. Antypas. "They are common in patients, and the data suggests they may actively contribute to more unfavorable clinical outcomes."
These findings thus challenge a popular idea in infectious disease research that blocking
quorum sensing is always beneficial. "The results show that in infective endocarditis, inhibiting
quorum sensing can actually harm the host by promoting biofilm growth," explains Kimberly Kline, full professor in the Department of Microbiology and Molecular Medicine at the Faculty of Medicine, UNIGE, and visiting researcher at SCELSE (NTU), senior author and co-corresponding author of the study. "Understanding when and where bacterial communication is beneficial or detrimental to the patient will be essential for designing smarter therapies."