Scientists are often placed in the role of Cassandra – because of their expertise and knowledge they may see potential serious problems on the horizon, but may also find it challenging to convince the general public. Sometimes they are working uphill against vested interests. Often scientists will warn against possible problems that they then work to prevent, and when successful it seems like their warnings were unwarranted. Or they may simply be calling for preparation for a possible event, like an epidemic, that still probably won’t occur but you should be prepared ahead of time in case it does.

Also, as science communicators we don’t want to overhype potential problems. It can be a delicate balance. With all that in mind, it is probably difficult to overstate the potential risk of antibiotic resistance. This is one of those looming issues that I genuinely worry about, but gets too little attention, if anything, in the media. It is also a manageable problem – there are things we can do to mitigate antibiotic resistance, if we take the issue seriously enough.

The World Health Organization summarizes the problem in stark terms:

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, gonorrhoea, and foodborne diseases – are becoming harder, and sometimes impossible, to treat as antibiotics become less effective.

Where antibiotics can be bought for human or animal use without a prescription, the emergence and spread of resistance is made worse. Similarly, in countries without standard treatment guidelines, antibiotics are often over-prescribed by health workers and veterinarians and over-used by the public.

Without urgent action, we are heading for a post-antibiotic era, in which common infections and minor injuries can once again kill.

I don’t think they are overstating the problem.

The cause of antibiotic resistance is fairly easy to understand. Bacteria reproduce very quickly in large numbers. When someone takes an antibiotic, that provides a selective pressure towards resistance. If any individual bacterium has a gene which provides resistance to the mechanism of that antibiotic it will tend to survive the treatment and then reproduce a new generation of resistant bacteria.

Bacteria also have the ability to swap genes, so that genes are not just passed from parent to offspring, but horizontally to other bacteria in a process called conjugation. Bacteria may contain plasmids, which are loops of DNA. Those plasmids can be copied from one bacterium to another. A plasmid may contain one or even multiple genes that confer resistance – and so in one conjugation event a bacterium may receive resistance to multiple antibiotics.

The existence of bacterial plasmids with multiple resistant genes is a problem, because if they are exposed to one of the antibiotics to which they are resistant, that will favor the proliferation of the bacteria with plasmids that confer multiple resistance.

There is one potential bright spot in all this. Genes that confer antibiotic resistance often come at a price. They may make it more difficult for the bacteria to reproduce, or force them to expend more energy. That is why they don’t have the feature in the first place. The selective pressure of antibiotics is necessary to favor the more costly feature. The hope is that in the absence of selective pressure from antibiotic, the resistant features will tend to fade away.

However, a new study suggests that this may not always be the case. Researchers looked at costly antibiotic resistance features in various strains of E. coli. They followed them for over a month and found that strains were able to maintain even costly antibiotic resistance in the absence of antibiotics if they contained plasmids. The key is the conjugation rate – how frequently do bacteria exchange plasmids? The research found that, at least in these strains, the rate was high enough to maintain antibiotic resistance even in the absence of antibiotics.

This research suggests that limiting antibiotic use may not be enough to reverse existing antibiotic resistance. Of course, limiting use is essential to slowing the development and spread of resistance. This is the primary mechanism by which the medical community is trying to combat resistance, but even here we are not doing enough. Antibiotics are still massively overprescribed. Some countries allow for over-the-counter antibiotic use, and it is common for the public to take them for viral illnesses. Antibiotics are also heavily used in the farming industry.

Even if we achieved our goal to properly limit antibiotic use, and educated practitioners to optimally prescribe antibiotics, the current research suggests this may not be enough to reverse some types of resistance. However, the same research suggests there may be more active interventions that will.

There are potential drugs that can limit conjugation or induce bacteria to lose their plasmids. For example, a 2015 study identified features of synthetic fatty acids that were effective conjugation inhibitors. This would limit the horizontal spread of plasmids among bacteria, and therefore limit the spread of resistance.

Another approach is to prevent plasmid replication. Researchers are looking at ways to exploit the existing compatibility system in bacteria toward this end. Since bacteria are so promiscuous with their genes, they need mechanisms to know when plasmids are incompatible with their other DNA. You could essentially trick a bacterium into thinking its plasmid is incompatible, and therefore when the bacteria reproduces it will not replicate the plasmid. The plasmid will therefore be lost to the next generation. These treatments would not just limit the spread of resistance, but cause a population of bacteria to lose their resistance.

What all of this research suggests is that we should not only be researching novel antibiotic mechanisms, we should be investing in research into drugs that inhibit plasmid conjugation and induce plasmid loss. These treatments can reduce the spread of resistance, and even potentially reverse resistance. Such treatments could be given alongside antibiotic regimens, or used in farming or similar contexts to limit the development of resistance.

My hope is that this type of research will eventually lead to a situation in which all those scientists and science-communicators who warned about the coming post-antibiotic era will look like Cassandras. Rather than getting the credit for identifying and then preventing a major problem, people will either forget them or falsely think the warnings were overhyped to begin with. But I will take that fate if it means avoiding a post-antibiotic era.


Posted by Steven Novella

Founder and currently Executive Editor of Science-Based Medicine Steven Novella, MD is an academic clinical neurologist at the Yale University School of Medicine. He is also the host and producer of the popular weekly science podcast, The Skeptics’ Guide to the Universe, and the author of the NeuroLogicaBlog, a daily blog that covers news and issues in neuroscience, but also general science, scientific skepticism, philosophy of science, critical thinking, and the intersection of science with the media and society. Dr. Novella also has produced two courses with The Great Courses, and published a book on critical thinking - also called The Skeptics Guide to the Universe.