Vancomycin: last line of defence

One of the most important discoveries of the 20th Century was antibiotics: chemicals that kill bacteria but not their human hosts. It changed the shape of human society as people began to survive septic cuts, everyday horrific infectious diseases, syphilis and tuberculosis.

The world we live in is almost unimaginably healthy compared to 100 years ago, largely thanks to this discovery. Death in childhood is rare rather than commonplace. Plagues – sweeping epidemics of often bacterial infection – are also far less common, and the coupling of antibiotics and antiseptics is so effective in fending off opportunistic bacteria during invasive surgery that surviving it is no longer the miracle it once was.

With antimicrobial resistance very much our minds, this Christmas our chosen antibiotic is Vancomycin: the last line of defence in fending off bacteria.

Exploiting competition

Vancomycin, like many antibiotics, is sourced (somewhat counter-intuitively) from bacteria. Essentially, humans nick weapons from the perpetual warfare between competing bacteria, and use them to create more precise instruments.

Bacteria are constantly vying with each other for resources to gain the upper hand. Many of them are equipped for sophisticated chemical warfare: releasing hideous poisons to kill other bacteria, or at least supress their growth. Sometimes the chemical combatants include fungi, but the basic modality is always the same: secrete a powerful chemical that directly interferes with the day-to-day business of your competitors (but not your own), and keep pumping it out until you own the field.

By isolating these poisons, we put bacteria’s chemical arsenal to work for our own ends. In the case of Vancomycin, some very clever people isolated the bacteria that manufactures it from a soil sample from Borneo.

Vancomycin makes it almost impossible for certain types of bacteria to build a cell wall. It binds to a commonly used connector (a complex peptide, like a protein polymer) halfway through the wall-building process, and prevents the wall components from sticking together (i.e. crosslinking). Because many bacteria use the same type of connector, the strategy is effective for defeating a broad range of competitors.

Vancomycin is a particularly effective antibiotic due to its site of action. Cell-wall ‘construction’ must happen outside of the cell, so the victim is prevented from resisting by pumping out the chemical poison – the most common form of defence.

What, no ribosome?

Vancomycin looks like a rather complex peptide, but full of oddities, with strange amino acids present. That’s because it’s not made in a ‘normal’ manner, that is, printed out by a ribosome. It is made instead via non-ribosomal synthesis involving a chain of complex proteins – each of which is hundreds to thousands of amino acids long – linking up Vanomycin’s bespoke amino acids in a highly specified manner.

This is bafflingly inefficient and complex. But then, when you’re in an arms race with your soil-bound competitors, no metabolic or energy expense is spared to be top bacteria in your region.

Clever synthesis

Amazingly, human chemists can imitate the sophisticated process of making Vancomycin, and synthesise it directly. That is certainly not true for every antibiotic or chemical – sometimes we still need to get bacteria or fungi to make things for us.

This precious chemical arrives in hospital every day, only to be administered if all other antibiotics fail. It has to be given intravenously. as it can’t be absorbed via the gut. Hundreds of thousands of lives are saved every week thanks to this re-purposed weapon of bacterial chemical warfare.

The Resistance

But dark clouds are gathering on the horizon: there are now more microbes that are resistant even to this last line of defence. Some bacteria are working out how to tweak their cell wall to prevent Vancomycin from messing it up.

Sadly, many life-scientists and chemists have been concentrating their efforts on making drugs for more common, non infectious diseases. But if a bacterium can pull together several modes of resistance into one package, it could easily win the war on a massive scale, sweeping across world and putting humans firmly back to the pre-antibiotic-medicine era – with all its hardship and untimely death.

Forward-thinking public research institutions are aware of this danger, and invest heavily in research to find the next ‘last resort’ antibiotic. Responsible research and policy programmes also pursue ways to improve the stewardship of our current arsenal. For example, the excessive use of antibiotics in agriculture creates a hyper-competitive environment in the soil, wherein many more bacteria evolve stronger and stronger resistance in order to survive.

Vancomycin and other antibiotics have held the bacterial army at bay for a while, but the clock is ticking, and the enemy is at the door.