New weapons in a deadly war

Antibiotic Resistance
A very real threat, poised to be humanity’s biggest killer by 2050.

I have many fond memories of playing the game Civilisation V. For those who don’t know, the premise of the game is that you take on building a civilisation up from the first city up to eventual victory or loss to other civilisations in the world. You control the scientific, artistic and productive output of your cities, manage their resources and resource development, engage in diplomatic relationships, all to try and establish your dominance. Being as realistic as possible, nations also declare war on one another, sometimes turning into aeons-old stalemates between neighbouring nations lasting from Ancient Roman days of chariots and warriors, all the way up to the modern era.

Along the way, you continually upgrade your weaponry and defence as your research and scientific knowledge increases. Axes and arrows become highly ineffective against pikes and lances. Stone walls are an amazing invention … they keep out invaders, hinder their progress and make it difficult for the enemy to capture your cities.

But over time, once-new technologies become less useful- the prized wall-building technology becomes entirely obsolete with the discovery of gunpowder.

 

We are in a long war with bacteria. For centuries they’ve been winning, claiming millions of lives throughout history. Hindered by various medical techniques, but aided by poor hygiene and a misunderstanding of what they actually were.

But in 1928, we built our first stone wall.

Penicillin, a miracle drug, saving countless lives that were otherwise cut short by infection. Other types of antibiotics followed soon thereafter. For some years, we were relatively safe in the skirmishes that we battled against each other, the human race against the collective of pathogenic bacterial species.

But history repeats its pattern in the natural world. The bacteria discovered gunpowder: antibiotic resistance, where our miracle weapons of antibiotics were rendered utterly obsolete, and giving the bacteria the chance to once more emerge victorious.

 

Returning to the analogy, stone walls became obsolete when faced with gunpowder, but gunpowder provided a means to build long-range weapons to fend off invaders before they reached cities. Later technologies produced airplanes and bombers, military forts and nuclear shelters.

One method of defence proved to be obsolete in the face of modern technologies (walls vs gunpowder), so science progressed to provide a new solution to fend off invasion, not simply a bigger wall, but a different method entirely to adapt to the change.

 

If antibiotics today are like our stone wall, a great defence against harmful and dangerous pathogens and if antibiotic-resistant bacteria are the gunpowder that’s making them obsolete, then we’re due to discover a new technology.

“And what is it?” You might rightly ask.

We’re working on multiple new weapons, some better, some worse, and one recent one in particular that’s looking particularly promising. A toxin that selectively kills antibiotic-resistant bacteria.

 

If it works, it’ll kill all the invaders and avoid collateral damage to our own beneficial microbiota (think, the citizens living in the civilisation that we’re protecting). What’s even better is that in early trials, there’s an incredibly low rate of resistance from the bacteria, only 10-6 – 10-8, in their data. (compared to early trials of antibiotics, in which resistance was observed very early on. For info, read this open-access paper, starting at the section “A little antibiotic history”). 

 

Bacteria regularly share genes in a process called conjugation, and this is part of the reason why antibiotic resistance is so damaging- one bacteria mutates and develops a resistant gene and goes to share it with all the neighbouring bacteria.

This new weapon (yes, the authors even call it a weapon) works similarly. It is a gene that encodes for a toxin and an antidote, but through some very clever biotechnology, non-resistant bacteria produce the toxin and antidote and are unharmed by the drug. Antibiotic resistant bacteria produce only the toxin, and are therefore killed by their own production of it.

The elegant beauty of this solution means that because all less-harmful bacteria (the ones that can still be treated by normal antibiotics) are protected, natural selection won’t act on any of these bacteria to preserve a different mutation to protect against the poison. So if this technique was used in conjunction with current antibiotics, it would likely have far greater success in curing the infection. Only if an already-resistant bacterium developed a mutation against the toxin would there be any additional resistance, and this occurred only in rates of 1 bacterium per 10 million.

This means that this method would be highly effective in resistant populations of below 10 million bacteria, but fairly useless in large populations, as bacteria would simply share the new adaptation and become resistant again, waiting for a new technology.

 

So it’s one step further, with more steps needed, but it looks to be a pretty effective weapon so far!

 

Read more about antibiotic resistance from this blog in the post-antibiotic world series:  A post-antibiotic world- What is it?

A post antibiotic world- What’s the big deal?

A post-antibiotic world- What can anyone do about it?

A post-antibiotic world- The Future

 

Paper is available from Nature, but is not open-access. A summary article is available here

 


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