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Genes for antibiotic resistance

The views expressed are those of the author and are not necessarily those of Scientific American.


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Ever since the discovery and marketing of penicillin in 1928 by Alexander Fleming, bacteria have been developing resistance to antibiotics at an alarming rate. In many cases, resistant bacteria can be found lurking even before the new drug hits the market, making it only a matter of time before it becomes widespread.

Bacteria that are resistant to multiple antibiotics are commonly known as ‘superbugs’ and on one particularly virulent  such bug is vancomycin-resistant Enterococcus faecium or VRE. VRE is an intestinal bacteria that lives in the human gut and is resistant to many antibiotics including vancomycin, which is currently one of the more powerful antibiotics used to treat other superbugs such as MRSA.

superbug!

Superbug! Original bacteria from wikimedia commons. Fearsome MS paint skills (c) me.

Due to the vancomycin resistance, the antibiotic most commonly used to treat VRE is a drug called daptomycin. A worrying development is that the bacteria are also starting to develop daptomycin resistance, not as a free-living resistant strain but actually during antibiotic treatment. Patients with daptomycin-sensitive bacteria are being given the antibiotic, and daptomycin resistance is developing inside them.

In order to try to understand how this resistance develops in response to treatment, researchers at The University of Texas Health Science Center isolated bacteria from a patient before and after treatment, successfully collecting both daptomycin-sensitive strains (from before treatment) and daptomycin-resistant strains (from after). By sequencing the genomes of both bacteria they could identify which genes had changed to provide the resistance.

Enterococcus faecalis (a related bacteria) under an electron microscope. The 'coccus' means that these are sperical bacteria (rather than rod-shaped or spiral ones). The 'faecalis' gives a hint as to where they were first found ...

The researchers discovered that there were two main genes responsible for the development of daptomycin resistance. The first (LiaF for those interested in such things) affects the composition of the cell membrane. By creating more of a positive charge at the cell surface (by modifying the compositions of phospholipids) the bacteria can partially repel the negatively-charged daptomycin making it harder for the drug to interact with the bacterial cell surface.

The second gene (gdpD) appears to be activated slightly later than the liaF and is involved in the synthesis of cell membrane components. Activation of this gene would therefore also lead to a substantial change in the cell wall composition, preventing the entrance and activation of the daptomycin. Whether these genes represent a specific response to the presence of the antibiotic or a more generalised bacteria stress-response is not yet known.

The discovery of mechanisms of resistance isn’t just for medical interest, it can also play a part in designing new drugs or adjuvants (substances added to a drug to make it more potent). With daptomycin, the resistance mechanism appears to be concentrated around the cell wall, and the way the cell wall interacts with the drug. Chemical modification of the antibiotic may produce a form of daptomycin that is able to interact even with the resistant cell wall, providing a much-needed form of attack against the VRE superbug.


Ref 1 = Arias CA, Panesso D, McGrath DM, Qin X, Mojica MF, Miller C, Diaz L, Tran TT, Rincon S, Barbu EM, Reyes J, Roh JH, Lobos E, Sodergren E, Pasqualini R, Arap W, Quinn JP, Shamoo Y, Murray BE, & Weinstock GM (2011). Genetic basis for in vivo daptomycin resistance in enterococci. The New England journal of medicine, 365 (10), 892-900 PMID: 21899450

S.E. Gould About the Author: A biochemist with a love of microbiology, the Lab Rat enjoys exploring, reading about and writing about bacteria. Having finally managed to tear herself away from university, she now works for a small company in Cambridge where she turns data into manageable words and awesome graphs. Follow on Twitter @labratting.

The views expressed are those of the author and are not necessarily those of Scientific American.





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  1. 1. c.boucher@erasmusmc.nl 10:17 am 11/24/2011

    your function forwarding your articles by email does not seem work

    Link to this

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