Commonground
Senior Moderator
Discover how bacteria become resistant to antibiotics
Wed, 17/12/2008 - 15:40
For its effectiveness in curing diseases that were fatal in other times, not so long ago antibiotics were magical aura of drugs.
Today, bacterial resistance is a real headache for sanitarista. But at least for now researchers Argentines won a round in the fight against pathogenic microorganisms: a work that today is published in the scientific journal Proceedings of the National Academy of Sciences achieves unravel one of the keys to bacterial resistance to antibiotics: show through structural studies, biochemical and microbiological where they recorded the molecular changes that allow the microorganisms to deactivate these drugs.
Bacteria, however, were commissioned to prove otherwise. International data indicate that up to 70% of the pathogens that cause lung infections are resistant to one of the first-line antibiotics and up to 60% of hospital infections are caused by resistant microbes.
"From that, half a century ago, Darwin published On the Origin of Species, the word 'evolution' refers to the process of genetic changes that lead to the emergence of new species and their adaptation to different environments-count Alejandro Vila, of the Institute Molecular and Cellular Biology of Rosario, and from Conicet the National University of that city, and Pablo Tomatis, author of the work.
In his attempt to understand the mechanisms of resistance of pathogenic bacteria to antibiotics, Vila and Tomatis working on some enzymes (proteins that catalyze chemical reactions) calls metalobetalactamasas that confer this capacity. That is, is defended by the bacteria to evolve this protein, which means that an entire body depends on a protein, a molecule.
The scientists replicated that procesoin vitro, adding larger amounts of antibiotics and inducing mutations in the protein.
"Emulated in the lab the natural process of evolution of this protein-Vila says. We had already seen that we could have a bacteria more resistant to antibiotics by evolving beta. In this work, we managed to develop one of these enzymes in the laboratory and we obtained more efficiently. "
The result surprised the "One would expect mutations at sites of contact with the antibiotic. It is rare that the changes that make the enzyme off more quickly antibiotics occur far from the site where he joins them, something that would have been impossible to rationally predict based on conventional approaches. It's an idea that goes against intuition. "
Isolating a group of mutant proteins, the researchers charted its metallographic structure and were able to visualize each of the sites where the protein is evolving, what they do and how to connect with each other.
"We see very weak interactions that go from one point to another of the protein and give you a lot of flexibility so that you can open and close much faster in the cavity where it joins with the antibiotic-Vila said. What surprise is that it does so at a distance. "
The beta of a model system to study the evolution of proteins in general and also produces other findings.
"We showed that these proteins mutate to be done in the lab predict future scenarios of resistance and open the door to the design of new antibiotics," says Vila. "Our idea is to anticipate developments. We can anticipate in what direction will be resistance of the bacteria, so that this knowledge would be predictive. "