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Op-Ed: Princeton’s ‘Irresistin’ works on all resistant bacteria

“Molecular antibiotics” is a synonym for “tough science”. They’re new to medical science, and they’ve taken a while to get going. This new breakthrough is in many ways a vindication of the long saga of an almost totally different approach to antibiotics and delivery of antibiotics.
Science Daily has a very clearly laid-out article on the Princeton research. This is a case where “interpretation” might blur the issues, so it’s best to read the core information without possibly misleading commentary. Please read it patiently because it explains in depth important principles which need to be properly understood. The basics are straightforward. The benefits, however, extend across the entire field of resistant bacteria, and that’s what I’d like to explore.
The very grim resistant bacteria catastrophe saga
Antibiotics were the wonder drugs of the 1940s-80s. They cured dangerous diseases like nothing ever had before. The bacteria, however, hit back hard, and some of the world’s worst diseases, like tuberculosis, became resistant. The notorious and extremely dangerous Golden Staph, in particular, became literally famous for its resistance. Resistant bacteria are very tricky and their evolution and development read like a good science fiction story.
It’s fair to say medical science was stunned, then immediately horrified. Antibiotics were underpinning basic treatments and procedures. They were failsafes for disease control and procedures like surgical infections, for example.
Medical facilities scrambled to try to find any sort of in-house method of ensuring sterility, but it was a thankless task. Only a handful of new antibiotics were working at all on these diseases, and not always as new strains emerged.
It didn’t take researchers long to realize they were dealing with a very new ballgame. The problem was that alternative methodologies didn’t really exist, except perhaps in theories. The original antibiotic methods seemed truly useless.
Also stuck in the mix was the inevitable communications problem – “Antibiotic” must mean new antibiotics, not new methods. It’s an understandable issue when you’re talking about how to do something with only one word to work with. So many new conventional options were researched, leading precisely and infuriatingly nowhere. (Grammatically, molecular antibiotics are literally antibiotic, but in practice, they’re a totally new approach. They’re barely related to old-style antibiotics except in name.)
Meanwhile, the resistant bacteria were (and in effect still are) literally out of control. If serious cases were low-ish in numbers like tens or hundreds of thousands of various degrees of difficulty, they spread worldwide in a decade. At one stage, resistant bacteria were so critical an issue that the medical news was literally swamped with incidents. Hospitals were at their wit’s end frantically trying to find ways to manage these things.
The medical dollar bottom line was also in the picture at this point. The cost and sheer scale of risk was more than horrific, and it was quite real. Resistant bacteria can do more than kill. They can put people in hideous medical conditions requiring a lot of expensive and extremely time-consuming care. This care does help, but may not be able to cure the conditions. The sheer practical strain of treatment on the world’s health systems alone became a true issue in itself. That’s pretty much the state of play at the moment.
The rise of molecular antibiotics
Molecular antibiotics can be seen as a mix of new science and a horrifying lack of options. The big “biology boom” since the 1990s has evolved about as fast as the resistant bacteria. New science, new techniques, gene technologies and more have contributed to what is basically a completely reworked framework for research.
Most importantly, molecular technologies have been very much part of this evolution. Previous generations of biology were largely chemistry-based. Conventional antibiotics are almost entirely chemical. They kill by poisoning bacteria. When they work, they’re highly effective. When they don’t, the patients are at serious risk. The resistant bacteria can trick conventional antibiotics, and/or simply be in a form where the chemistry bounces off.
The new molecular approach to antibiotic science came partly from the ability to image antibiotic processes, and partly from a new, structural line of attack becoming visible. Researchers could now see how antibiotics worked or didn’t work.
Top research institutions like MIT have also been working on molecular antibiotics. The new wave of research is delivering fascinating, and effective results. MIT’s Halicin, for example, is another approach based on this science. (These very diverse different approaches are also a good illustration of the agility and flexibility of molecular biology.)
Princeton’s Irresistin
This methodology is where the penny dropped when it came to resistant bacteria. The Princeton researchers tried a molecular approach they’ve called Irresistin, physically piercing the bacterial cells and injecting a poison to destroy folate in the cells. They discovered that Irresistin worked on all the worst resistant bacteria.
This is a breakthrough and a half as a methodology. The mix of barrier-busting and targeting is a good all-cases scenario for any kind of bacteria. Irresistin is clearly a general-purpose option for treatment, which is exactly what’s been missing.
To put this in context:
1. A general-purpose approach is a best practice anti-infection method typically used in just about all cases of bacterial infection. Irresistin just happens to be the do-everything-about-whatever method.
2. This type of all-round treatment can be produced as an off-the-shelf GP level antibiotic and as a good option for hospital management of infections. That makes it a commercially strong, practical solution.
3. Effective management of resistant infections will take a gigantic and truly murderous load off the health system. It’ll free up beds, improve recovery times, and help to stamp out resistant bacteria worldwide.
A bit of positive caution
It would be more than naïve to think that bacteria have run out of tricks just yet. After all, resistance is how they survived decades of saturation-level antibiotics. Epidemiology was the science that discovered the nature of resistant populations. So there’s plenty of work to be done in seeing how molecular antibiotics affect these huge numbers of resistant bacteria.
Will they die out? Will they find different vectors, and come back through species-hopping? What about malaria, and other highly contagious endemic mass-murdering diseases? It’s much too early to say, and molecular antibiotics are still in their infancy. Murphy’s Law is the most likely scenario, and it needs to be considered an inevitable factor in this environment.
There’s also still the issue of way too many chemical antibiotics in the macro-environment, which could lead to evolving resistance of different types on a statistical basis. The good news there is that it’s now much easier to spot resistance thanks to better, more responsive science and pathology.
Molecular biology is proving that there are major chinks in the armor of these dangerous pathogens. Strategically, a worldwide approach is required to really manage the resistant bacteria. Now is the time to go on the attack and beat these threats down.
Medical science may have other things to do, and soon enough. The rise of new viruses is likely to consume a lot of resources for research and health. If the bacteria can be finally pinned down, these emerging threats will be easier to manage. That’s the legacy of good medicine – You solve the problems so you can deal with the other problems.

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Editor-at-Large based in Sydney, Australia.

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