Novel Chemical Complex May Deliver Breakthrough in Antibiotic-Resistant Infections

“Survival of the fittest”…

It drives who—and what—lives and thrives to reproduce, shaping and strengthening adaptive traits through successive generations. From the tiniest life form to the most complex, selective pressure operates across every species on Earth.

But not all generations are created equal. When we look at the number of opportunities bacteria have to mutate and survive attacks by antibiotics, it becomes easier to understand why some bacteria overcome the pharmaceutical onslaught and actually become stronger.

The “generational lifespan” of a single bacterium (the period in which it lives as an individual cell before dividing) is typically twelve minutes to twenty-four hours. Every division offers the chance to mutate and produce a cell more able to resist a drug designed to kill the organism.

One human lifetime of seventy-nine years, then, represents 57,670–3,460,200 generations in bacterial life. That’s a lot of opportunities to defeat medicine. And in the past fifty years, hundreds of millions of generations of bacteria have begun to win the battle, creating “superbugs” that are resistant to most antibiotics.

In the meantime, humans have introduced…zero new antibiotics. In 2018, the World Health Organization put it bluntly:

Antibiotic resistance is rising to dangerously high levels in all parts of the world. New resistance mechanisms are emerging and spreading globally, threatening our ability to treat common infectious diseases. A growing list of infections – such as pneumonia, tuberculosis, blood poisoning, gonorrhea, and foodborne diseases – are becoming harder, and sometimes impossible, to treat as antibiotics become less effective.

The problem is stark: An EU Review on Antimicrobial Resistance predicts that, without further development of effective treatments, deaths from resistant superbugs will rise from 700,000 in 2014 to more than 10 million by 2050.

Tear Down These (Cell) Walls: How Ruthenium Compounds Kill Bacteria

Enter a new investigational pharmaceutical compound that attacks antibiotic-resistant bacteria in a completely novel way: By targeting and weakening the organism’s best defenses, its cellular walls, causing them to burst.

The gram-negative bacteria that cause salmonella, pneumonia, urinary tract infections, gonorrhea, chlamydia, and other nasty bugs in humans have been historically hard to treat because their cellular walls are especially well-insulated, with double-walled cellular structures that make it hard for therapeutic drugs to penetrate. But a new pharmaceutical compound derived from a rare metal, ruthenium, is showing extraordinary promise (in the petri dish, at least) by weakening those very cell walls and eventually causing them to burst. (Investigators know the mechanism of action because the compound itself glows when exposed to light; they can actually view its action in real time within the microscopic structures of a bacterial cell.)

Development and investigation of the compound is still in its earliest phases. The next step is to study the intervention’s action in mammals. However, the researchers are optimistic, explaining, “We played about with the structure and tried to make it so it would be preferentially taken up by the bacteria. We ended up with something that was toxic towards bacteria, particularly gram negative bacteria, and not toxic towards humans.”

The news comes at a particularly concerning time. Overprescribing of antibiotics, incomplete courses of the drugs, and massive use of antibiotics in livestock populations have all contributed to the selective pressures that have resulted in antibiotic resistance. The problem is so severe it triggered the United Nations to launch a global action plan “to ensure, for as long as possible, continuity of successful treatment and prevention of infectious diseases with effective and safe medicines that are quality-assured, used in a responsible way, and accessible to all who need them.”