Antibiotics play a critical role in treating infections caused by bacteria. However, there are times when they do not work as expected, even if the bacteria are not resistant. A recent study published in the journal Nature by researchers from the University of Basel questions the traditional belief that a small number of particularly tough bacteria are to blame for the ineffectiveness of antibiotic treatments.
Antibiotics are essential for treating bacterial infections. However, their effectiveness can sometimes come into question, even when bacteria do not exhibit resistance. A recent study in the journal Nature from researchers at the University of Basel is challenging the common notion that a minor group of exceptionally robust bacteria causes the failure of antibiotic treatments.
In certain bacterial infections, such as those caused by Salmonella, antibiotics might not work as well as anticipated. Historically, scientists thought that dormant bacteria, known as persisters, were the culprits behind treatment failures, as they can survive antibiotics and lead to recurring infections. In response, researchers have been developing new therapies focused on eradicating these dormant bacteria.
However, Professor Dirk Bumann and his team at Basel’s Biozentrum are challenging this widely accepted idea. “Antibiotic failure isn’t merely due to a small group of persisters. In reality, most of the Salmonella bacteria present in infected tissues are tough to eliminate,” Bumann states. “Our research indicates that standard laboratory tests for antimicrobial clearance may give misleading information, leading to an impression that there exists a small group of exceptionally resilient persisters.”
Nutrient deprivation boosts Salmonella survival
The researchers conducted experiments on mice infected with Salmonella, as well as in laboratory models that mimic biological tissues. A common defense mechanism of the body against bacteria is to limit nutrient availability. Their findings suggest that this nutrient deprivation is a major factor contributing to the survival of Salmonella during antibiotic treatments. The researchers believe this may also apply to other bacterial infections.
“When nutrients are scarce, bacteria tend to grow very slowly,” Bumann explains. “While this might seem beneficial, it’s actually problematic because most antibiotics are effective only against bacteria that are actively growing. Consequently, the drugs are less effective, which can lead to relapses, even after extended treatment.”
Real-time tracking uncovers errors in understanding
The researchers employed a novel technique to observe the effects of antibiotics on individual bacteria in real-time. “Our results showed that almost the entire population of Salmonella can survive antibiotic treatment for long periods, not just a small group of exceptionally tough persisters,” remarks Dr. Joseph Fanous, the lead author of the study.
Typical methods used to measure bacterial survival worldwide have significant drawbacks, as they offer indirect and delayed assessments, leading to misleading conclusions. “Traditional methods underestimate the number of surviving bacteria,” Fanous adds. “They also create a false impression of the existence of very resilient persister groups that aren’t really there.” This misunderstanding has affected bacterial research for years.
Innovative tools for antibiotic research
The implications of these discoveries could significantly alter the landscape of antibiotic research. “Our findings underscore the necessity of observing bacterial responses and antibiotic interactions in real-time and under conditions that closely resemble the body’s environment,” Bumann emphasizes. “In a few years, advanced methods, such as real-time single-cell analysis, should ideally become the norm.” Shifting the focus from persisters to understanding the consequences of nutrient deprivation is a crucial advancement toward better treatments for hard-to-treat infections.
This project is part of the National Center of Competence in Research (NCCR) “AntiResist.” The initiative aims to explore new strategies to tackle bacterial infections, with Dirk Bumann serving as one of the directors of NCCR “AntiResist.”
