Resistant bacteria combatted with known antibiotics

Friday 18 Sep 20

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Morten Otto Alexander Sommer
Scientific Director
DTU Biosustain
+45 21 51 83 40

It is possible to fight resistant E. coli bacteria by combining two widely known antibiotics.

 

 

One way to circumvent resistance is to find new ways of using existing antibiotics—something the Bacterial Synthetic Biology research section at DTU Biosustain has been investigating. 

The research team has focused on the multiresistant E. coli bacterium—ESBL—which hampers the treatment of urinary tract infections. However, as it turns out, the bacterium’s resistance can be exploited in the treatment of the infection. This is done by combining two commonly used antibiotics—mecillinam and cefotaxime—as the bacterium’s resistance to one, ‘triggers’ the microorganism’s sensitivity to the other.  The increased sensitivity of the bacterium makes it possible to eradicate it. The phenomenon, which is widely known, is called ‘collateral sensitivity’.

Old antibiotics in new bottles

The research team at DTU Biosustain found that the resistance is linked to mutations in a specific gene in ESBL—namely the CTX-M-15 gene. CTX-M-15 mutations are quite widespread globally and limit the ability of doctors to effectively treat urinary tract infections. In the lab, the research team examined combinations of antibiotics.

The advantage of using mecillinam and cefotaxime as a combination treatment is that both drugs can be given as pills and are already approved. New antibiotics rarely come on the market, forcing doctors to find new ways to use existing medicines precisely to avoid resistance.

Personalized treatments the goal

50 per cent of women worldwide report having had urinary tract infection at some point in their lives, according to the World Health Organization (WHO). This new combination treatment therefore holds tremendous potential.

That said, the treatment only works with this specific strain of ESBL with the specific mutation. It is therefore crucial to know the mutation profile of the pathogenic bacteria in order to choose the right combination strategy.

“DNA sequencing samples from patients are necessary to tailor antibiotic treatment based on the mutation landscape,” says Scientific Director Morten Sommer, who heads Bacterial Synthetic Biology.

The method allows other researchers to study other resistance genes to find new antibiotic combinations, thereby utilizing ‘collateral sensitivity’ to fight infections despite resistance.

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