The introduction of antibiotics into medicine revolutionised the way infectious diseases were treated. Between 1945 and 1972, average human life expectancy jumped by eight years, with antibiotics used to treat infections that were previously likely to kill patients. Today, antibiotics are one of the most common classes of drugs used in medicine and make possible many of the complex surgeries that have become routine around the world. In recent years, a body of publications in the microbiology field has challenged all previous knowledge of how this unique class of medicines kill bacteria.
“A slew of papers came out studying this phenomenon, suggesting that there is a general mechanism of killing by antibiotics,” said Kim Lewis, University Distinguished Professor in the Department of Biology and director of Antimicrobial Discovery Center at Northeastern University.
We have believed the fact that the three main classes of bactericidal antibiotics each have a unique way of killing bacterial cells—like specialised assassins each trained in a single type of weaponry. However, this new research suggested that all antibiotics work the same way, by urging bacterial cells to make compounds called Reactive Oxygen Species, or ROS, which bacteria are naturally susceptible to.
“If they were right it would have been an important finding that could have changed the way we treat patients,” said Iris Keren, a senior scientist in Lewis’ lab. “We chose to do the simplest and most critical experiment aimed at falsifying this hypothesis,” said Lewis. “Killing by antibiotics is unrelated to ROS production,” the authors wrote. The findings were corroborated by University of Illinois researchers in another study.
The team treated bacterial cultures with antibiotics in both the presence and absence of oxygen. Other than the gaseous environment, the two treatments were identical. There was no difference in cell death between the two populations. Before performing these experiments, Lewis’ team first looked at signals of a fluorescent dye, which previous researchers had used as an indicator for ROS levels. The team treated bacterial cells with a variety of antibiotics and measured the strength of this signal. Since antibiotics were presumed to increase ROS levels, one would have expected increased concentrations of antibiotics to correlate with stronger signals. However, Lewis’ group saw no such correlation.
“However, there’s a difference between correlation and direct observation,” Keren said. To support their observations with unequivocal data, the team members physically separated the cells that had stronger fluorescent signals from those with weak signals and treated them both with the same antibiotics. Both populations suffered from equivalent cell death.
“The research from Dr. Lewis’ group demonstrates that, contrary to current dogma, antibiotics apparently do not kill bacteria through induction of reactive oxygen species,” said Steven Projan, vice president for research and development at iMed and head of Infectious Diseases and Vaccines at MedImmune.”
We hope that this result will help Lewis and Keren to focus its efforts on understanding the true mechanisms of how antibiotics wipe out bacteria in order to effectively address chronic bacterial infections, one of the most pressing issues facing public health today.