DUEL BETWEEN HUMANS AND BACTERIA: will antibiotic therapy save humanity

Consultant at Jansen Capital Management

DUEL BETWEEN HUMANS AND BACTERIA: will antibiotic therapy save humanity

Photo by Charles Chen on Unsplash

The invention of antibiotics has helped save millions of human lives. However, over time, bacteria have developed superpowers, learning to defend themselves against the effects of medical drugs. But biologists are not giving up — they are calling on new and increasingly sophisticated killers of pathogens for help. The evolutionary battle between the most intelligent and the most prolific forms of life continues.

AN ACCIDENTALLY «REDISCOVERED» DISCOVERY

umanity had been using antibiotics for thousands of years without knowing the term. In Ancient Egypt and Ancient Greece, for example, moldy bread was applied to wounds to prevent infection. In Ancient Mesopotamia, the sick were treated with fermented soup. Sometimes even sour milk or spoiled meat was used. But it was only in the 19th century that European science discovered the bacteriostatic properties of the green mold Penicillium glaucum.

Even after this discovery, its miraculous effect remained long unnoticed — until 1928, when Scottish biologist Alexander Fleming accidentally introduced mold into his laboratory, where the penicillin it produced successfully destroyed staphylococcus bacteria. However, scientists at Oxford University were able to stabilize this substance only in 1939, which opened the way for penicillin to be mass-produced.

THERE ARE NOT THAT MANY EFFECTIVE ANTIBIOTICS

By continuously developing new generations of antibiotics, scientists have saved millions of lives. To date, there have been five generations, differing in their spectrum of activity and their resistance to bacterial enzymes. However, by the 1970s, the pharmaceutical boom associated with antibiotics had generally begun to subside. Science knows of about 2,000 types, of which roughly 600 have been described, and no more than 150 are in active use.

The belief in the «omnipotence» of antibiotics has given rise to several myths. The main misconception is that they work against viral infections. Unfortunately, antibiotics are powerless in the fight against viruses. However, they can treat a wide range of bacterial infections — fungal, respiratory, and urogenital. Some are even used in the treatment of malignant tumors.

THE MUTATING KILLER

Not so long ago, the victorious march of antibiotics across the planet began to face serious obstacles. Medicine has more or less learned to cope with the side effects of antibiotics, such as allergic reactions and microbiota imbalance. Antibiotic resistance, however, is another matter entirely. The problem is that bacteria have proven to be highly cunning creatures and have no intention of surrendering to the victor’s mercy.

At first, antibiotics easily destroyed bacterial cell membranes and genetic material. Over time, however, bacteria began to mutate, finding ways to adapt, causing antibiotics to lose their effectiveness at an alarming rate. Due to antibiotic-resistant bacteria, 1.1 million people die every year, and by 2050 this number is expected to reach nearly 2 million.

Today, antibiotic resistance has become a global problem that threatens advances in many areas of medicine, including surgery, neonatology, transplantology, and oncology. For example, up to 20% of births worldwide are performed via caesarean section. If antibiotics fail, the risks of such operations increase immeasurably.

ANTIBIOTICS? TOO EXPENSIVE!

Bacterial defensive mutations could be countered by discovering new classes of antibiotics. However, over the past 40 years, no such breakthroughs have occurred — scientists have only been modifying already known drugs. There are several reasons for this.

The first is that producing new antibacterial agents has become economically unprofitable. Developing a new antibiotic requires an investment of about $1 billion, and it will start to pay off only after an average of 23 years. The second reason is the incredible speed at which bacteria reproduce and adapt — something Fleming himself once complained about. By the 1940s, resistance to penicillin was already found in 14% of patients; in the 1950s, in 59%; and in the 1990s, in 95%.

From 2000 to 2010, global annual antibiotic consumption more than tripled — a trend that only helps bacteria improve their survival skills. A phenomenon known as superbugs has even emerged: microorganisms that have developed resistance to virtually all known antimicrobial drugs.

AN ANTIBIOTIC LYING UNDERFOOT

And yet, it is too soon to put a final period in the evolutionary duel between humans and bacteria. The human mind is no less cunning and powerful than bacteria’s instinct for survival. Scientists are reporting the discovery of next-generation antibiotics that can kill superbugs without harming the gut microbiome — or that can push bacteria «barricaded» against drug effects into committing suicide.

Very recently, the international scientific journal Nature reported the discovery of another innovative antibacterial compound. Completely non-toxic to humans, it can kill even those bacterial strains that have developed resistance to medical drugs. This new antibiotic, named «lariocidine» or LAR, belongs to the class of so-called lasso peptides.

Their molecular shape resembles a lasso — a rope with a loop at the end used by American cowboys to catch animals. Chance has accompanied antibiotic discoveries since Fleming’s time: scientists found this new miraculous molecule literally underfoot, after collecting soil samples in a Petri dish from the garden of a lab assistant at McMaster University in Hamilton, Canada.

A SUPER-KILLER FOR SUPERBUGS

For a year, researchers observed the development of this environment, and then introduced the gut bacterium Escherichia coli, which causes severe illnesses. That was when the LAR molecule revealed its powerful antibacterial activity. Lariocidine targets the bacterial ribosome as a highly attractive site — and antibiotic resistance against this structure is the hardest for bacteria to develop.

The LAR molecule damages the genetic code and prevents it from being read correctly, causing the ribosome to produce peptides toxic to the bacteria, which then die. Since lariocidine’s mechanism of action is fundamentally different from that of other antibiotics, pathogens have no resistance to it.

This was proven in experiments on mice infected with Acinetobacter baumannii C0286, often called the «Iraq bacterium» because infection rates peaked in military medical facilities during the Iraq War.

The «Iraq bacterium» is resistant to carbapenems — a new generation of antibiotics — but was defenseless against lariocidine. Now, scientists are focusing their efforts on turning the LAR molecule into a fully developed medicine.

Original research: