Posted on 02/06/2017 4:23:08 PM PST by 2ndDivisionVet
Antibiotics can still kill drug-resistant bacteria if they 'push' hard enough into bacterial cells, finds new UCL-led research funded by the Engineering and Physical Sciences Research Council.
The study, published in Nature Scientific Reports, opens up a promising new way of overcoming antibiotic resistance and could help scientists to design even more effective drugs.
"Antibiotics work in different ways, but they all need to bind to bacterial cells in order to kill them," explains lead author Dr Joseph Ndieyira (UCL Medicine). "Antibiotics have 'keys' that fit 'locks' on bacterial cell surfaces, allowing them to latch on. When a bacterium becomes resistant to a drug, it effectively changes the locks so the key won't fit any more. Incredibly, we found that certain antibiotics can still 'force' the lock, allowing them to bind to and kill resistant bacteria because they are able to push hard enough. In fact, some of them were so strong they tore the door off its hinges, killing the bacteria instantly!"
The researchers used sensitive equipment to measure the mechanical forces that four different antibiotics exerted on bacterial cells. They tested bacteria that were susceptible to antibiotics and those that had developed resistance. The antibiotics all exerted similar forces on susceptible bacteria, but the forces they exerted on resistant bacteria varied significantly. The antibiotics tested included vancomycin, a powerful antibiotic used as a last resort treatment for MRSA and other infections, and oritavancin, a modified version of vancomycin used against complex skin infections.
"We found that oritavancin pressed into resistant bacteria with a force 11,000 times stronger than vancomycin," says Dr Ndieyira. "Even though it has the same 'key' as vancomycin, oritavancin was still highly effective at killing resistant bacteria. Until now it wasn't clear how oritavancin killed bacteria, but our study suggests that the forces it generates can actually tear holes in the bacteria and rip them apart."
Oritavancin is a fast-acting antibiotic that can kill bacteria in 15 minutes, whereas vancomycin takes 6-24 hours. Vancomycin works by disrupting vital processes in bacteria so they slowly stop functioning and die. Although oritavancin is a modified version of vancomycin, the new study suggests that it kills bacteria in a completely different way.
"Oritavancin molecules are good at sticking together to form clusters, which fundamentally changes how they kill bacteria," explains Dr Ndieyira. "When two clusters dig into a bacterial surface they push apart from each other, tearing the surface and killing the bacteria. Remarkably, we found that conditions at the bacterial surface actually encourage clustering which makes antibiotics even more effective."
The team developed a detailed mathematical model to describe how antibiotics behave at the surface of bacterial cells. The model could be used to screen promising new antibiotics, identifying new drugs that can kill bacteria by using brute force.
"Our findings will help us not only to design new antibiotics but also to modify existing ones to overcome resistance," says Dr Ndieyira. "Oritavancin is just a modified version of vancomycin, and now we know how these modifications work we can do similar things with other antibiotics. This will help us to create a new generation of antibiotics to tackle multi-drug resistant bacterial infections, now recognized as one of the greatest global threats in modern healthcare."
The research was primarily funded by the Engineering and Physical Sciences Research Council (EPSRC), with additional support from UCL, the European Union and the National Institute for Health Research University College London Hospitals Biomedical Research Centre.
Fascinating development in the war between man and microbe. Thank you.
“The researchers used sensitive equipment to measure the mechanical forces that four different antibiotics exerted on bacterial cells.” I would like to see this “equipment” as it must be very, very small to put it lightly.
Electron Microscopes and their calculations were but estimates. The calculations may be right and perhaps not. I would suspect they are looking at the molecular bonding forces in the cell membrane of the bacterium and what is needed to force it apart. This is really rocket science with "wag" also known as "wild ass guess." I hope they are right.
Fascinating, thx.
Re: “Every breath, another five thousand fungal spores enter your body.”
And, 1% to 3% of your body weight is benign or symbiotic bacteria.
Did I forget to mention the mites that live inside your eyelash follicles?
Now if they can only use the same approach with viruses.
Exactly. An SEM cannot measure a “force.” If they can, it is news to me. Note the specifics are never mentioned but that was not the intent of the piece. A journal article will most likely do that, but even then they are very wanting.
I heard about those guys. What do they eat?
Surface mediated cooperative interactions of drugs enhance mechanical forces for antibiotic action
http://www.nature.com/articles/srep41206
Mites?
Some mites eat fungi.
But, eyelash mites, I don’t know.
Bacteria?
Just about everything.
Cell waste products, for certain, and they often initiate important stages in digesting different kinds of food.
We have bacteria on our skin that actually live by photosynthesis.
Don’t doubt that one bit. That Is a issue with those with Dry Eye Syndrome, baby shampoo is useless, add some Tea Tree oil about a 2 oz bottle to a bottle of baby shampoo, wash eyelash line, world of difference in the comfort of the eyes. Follow up with a very warm not hot moist compress. I make it up in small batches. My oil glands clogged up following Cataract implants and tear film was half what it should be. I’ve tried every artificial tear drop on the market that was preservative free, Similasan dry eye relief is all natural and works the longest and best. Refresh Lubricant was the WORST, gunked up the eye lids and you had to pull them apart. No I don’t wear eye make up.
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