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Most dead bacteria can sometimes be resuscitated as antibiotic resistant cells.
A protein that pumps toxic chemicals from E. coli Bacterial cells can save time for even almost dead microbes to become resistant to antibiotics. The protein, known as the AcrAB-TolC Multiple Drug Efflux Pump, does not work well enough to defeat the antibiotics by itself. But researchers reported in a report released on May 24 that enough antibiotic molecules would be extracted from bacterial cells to allow the production of true resistance proteins. Science.
Bacteria often exchange their DNA, including some genes for antibiotic resistance. Scientists have known for decades that antibiotic resistance genes are often carried on small circles of DNA called plasmids. Two bacteria that come into contact can transmit these plasmids from antibiotic-resistant cells to sensitive cells. But this was thought to happen when antibiotics are not available to kill sensitive cells.
The common wisdom is that treating bacteria with antibiotics should prevent bacteria from exchanging antibiotic resistance genes, says Kim Lewis, a microbiologist at Northeastern University in Boston, who was not involved in the study. At least, "Yesterday, that's what I would have told you," he says. "Today, after reading this newspaper, I must change my mind."
The bacterial geneticist Christian Lesterlin of CNRS-INSERM at the University of Lyon in France and his colleagues wanted to know more about how bacteria transmit antibiotic resistance. Genetically modified researchers E. coli to make fluorescent proteins that allowed the team to see microscopically in real time the exchange of plasmids by a bacterium and the manufacture of antibiotic-resistant proteins.
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VIVA RESISTANCE The researchers captured the E. coli bacteria becoming resistant to the tetracycline antibiotic. Some bacteria already contained a circular DNA fragment, called a plasmid, carrying the genes for antibiotic resistance. These resistant cells (green) transmit the plasmid to the sensitive cells (red). Once the plasmid is transferred (yellow dots), sensitive bacteria begin to make proteins making the microbes resistant to the antibiotic. The bacteria become more and more green when they become resistant to the antibiotic. |
The exchanges are fast. Within three hours, about 70% of sensitive people E. coli became resistant to the tetracycline antibiotic, discovered the Lesterlin team. When tetracycline was added to the bacterium, about a third of the microbes still sensitive also became resistant to tetracycline. "It was very, very surprising," says Lesterlin.
Once the bacteria have received the plasmid DNA, they still need to activate the resistance genes and produce the proteins that fight the antibiotics – in this case, a protein called TetA that pumps the tetracycline out of the bacteria . Tetracycline blocks the production of proteins. So, when the drug becomes available, bacteria that have not yet made TetA will almost be dead and should not be able to take advantage of newly acquired resistance genes, says Lewis.
But most dead bacteria are still slightly alive thanks to the multidrug pump, at least enough to sometimes extract some TetA proteins, which then export all the antibiotics and allow the microbes to recover their full life, have discovered the researchers.
The multi-medication pump has also helped the bacteria stay alive long enough to develop resistance to other antibiotics. Disabling or removing this pump has prevented bacteria from developing resistance. Drugs that deactivate this protein pump may be able to prevent the spread of antibiotic resistance through plasmids. But no drug of this type can still be used safely in people, Lesterlin said.
"There is no good news for human well-being" in the study, he says. "Better to know your enemy and his type of weapon."
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