Bacterial antibiotic new resistance: mechanism found (Introduction)

by David Turell , Friday, May 24, 2019, 15:28 (2010 days ago) @ David Turell

A specialized naturally existing membrane pump:

https://www.the-scientist.com/news-opinion/how-bacteria-become-drug-resistant-while-exp...

"A membrane pump found in most bacteria helps E. coli acquire drug resistance from neighboring cells even while they’re exposed to antibiotics, a new study shows.

"E coli is capable of synthesizing drug-resistant proteins even in the presence of antibiotics designed to cripple cell growth. That’s the finding by a group of French researchers reporting today (May 23) in Science. They also discovered how the bacteria manage this feat: a well-conserved membrane pump shuttles antibiotics out of the cell—just long enough to buy the cells time to receive DNA from neighbor cells that codes for a drug-resistant protein.

***

"The team made an educated guess as to why the cells were capable of this: many bacterial membranes are known to harbor a multidrug efflux pump known as AcrAB-TolC, which is capable of shuttling a wide range of antibiotics out of cells, and the scientists figured that it was getting tetracycline out of the cell before it could stop protein synthesis and cell growth.

***

"When functional, the AcrAB-TolC pump buys the bacteria time by keeping antibiotic concentrations just low enough for the cells to synthesize the resistance proteins encoded in the plasmid DNA, according to the researchers. In this case, it allows for the production of the TetA protein, which then shunts more tetracycline out of the cell. Ultimately, bacteria can become resistant while still under the influence of antibiotics.

***

"The findings are widely relevant, she says—for one, because AcrAB-TolC is so broadly conserved across bacteria, and also because the mechanism is not limited to tetracycline. Lesterlin and his colleagues demonstrated that the pump also allows bacteria to produce drug-resistant proteins in the presence of other antibiotics designed to stifle gene expression, such as the translation-inhibiting chloramphenicol, and the transcription-inhibiting rifampicin. This mechanism is relevant for so-called bacteriostatic antibiotics, which don’t kill but only stifle bacterial growth, Lesterlin adds. He doubts it will work for bacteriolytic antibiotics, which destroy bacteria outright before they can become resistant."

Comment: for me the key point is that Tetracycline is an antibiotic that was found originally in nature as a natural defense molecule made by a fungus. Therefore what bacteria can do when presented with tetracycline is a defense mechanism for them that many of them developed at the beginning of evolution, just as they developed horizontal gene transfer. But note the final paragraph: we can analyze every bacterial mechanism that can be attacked and should be able to defeat resistance. Our first approach of finding natural antibiotics in soil has run its course.