A Promising Approach

Friday, April 08, 2011

From opposite sides of the planet come really bad news and a ray of hope. Getting the bad news out of the way, yet another report of superbugs on the loose came, this time from India, the other day:

A gene that makes [bacteria] highly resistant to almost all known antibiotics has been found in bacteria in water supplies in New Delhi used by local people for drinking, washing and cooking, scientists said on Thursday.
As a story on the rise of antibiotic resistant bacteria pointed out some time ago, the loss of this defense against infectious bacteria would be a disaster for modern medicine.
Dr Livermore, whose grandmother died for lack of infection-killing drugs in 1945, is director of the antibiotic resistance monitoring and reference laboratory of the Health Protection Agency. Last year, the HPA put out an alert to medical professionals about NDM 1, urging them to report all suspect cases. Livermore is far from sanguine about the future.

"A lot of modern medicine would become impossible if we lost our ability to treat infections," he says. He is talking about transplant surgery, for instance, where patients' immune systems have to be suppressed to stop them rejecting a new organ, leaving them prey to infections, and the use of immuno-suppressant cancer drugs.

But it is not just an issue in advanced medicine. Antibiotics are vital to abdominal surgery. "You safeguard the patient from bacteria leaking into the body cavity," he says. "If you lose the ability to treat these infections, far more people would die of peritonitis." Appendix operations would carry the same risk as they did before Fleming discovered penicillin in 1928.
Fortunately, nanotechnology may be well on the way to providing an answer, by overcoming some of the limitations found in a couple of classes of molecules that were being investigated for their antibiotic properties:
[C]harged peptides like magainin can be difficult to work with. Charged polymers have proven to be preferable to peptides because their manufacture is easier and cheaper to scale up, and because they are less haemolytic -- they are better at killing bacteria than they are at killing red blood cells. But the fact that they are not biodegradable poses a problem when it comes to their use in humans.

[Fredrik] Nederberg et al. made charged polymers out of cyclic carbonates, which are nontoxic and biodegradable. Their degradation produces alcohol and carbon dioxide, and they degrade slowly, so they have prolonged antimicrobial functions inside the body and long shelf-lives outside of it. Because of their amphiphilic nature -- they have a positively charged region, which is hydrophilic, but also a hydrophobic region -- these nanoparticles spontaneously form small spheres in water, so they can hide their hydrophobic parts inside.

The enhanced charge of the spheres allows them to more efficiently bind to the bacterial cell wall than other antimicrobial polymers that act as single molecules. The nanostructures were effective against Gram-positive bacteria, methicillin-resistant Staphylococcus aureus (MRSA), and the fungus Cryptococcus neoformans, and had an efficiency comparable to that of conventional antimicrobials at their best, all while leaving red blood cells alone. [link to journal abstract added]
Test results with mice sound promising.

We're not necessarily out of the woods. I understand that drug development can be tricky, and human tests could always reveal some unforeseen problem. But setting aside those pitfalls and interference from the FDA, we may well see catastrophe averted.

-- CAV

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