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Content archived on 2024-06-18
Investigation into the Biological Cost and Adaptation of the Host to Antibiotic Resistance on mobile Genetic Elements in Enterococcus species

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Antibiotic resistance and loss of fitness

Antibiotic resistance in bacteria is one of the greatest challenges to modern medicine. An EU project has investigated the effects of carrying resistance genes on the bacteria themselves and its significance for antimicrobial resistance management.

Spread of antibiotic resistance between different bacterial populations is a worrying phenomenon. Horizontal gene transfer is responsible for movement of mobile genetic elements that can contain genes for resistance to antimicrobials. One such transferable gene, a conjugative transposon (cTn), Tn916, has been found in a wide range of bacteria. Tn916 is responsible for resistance to tetracycline and other antimicrobials. The EU-funded BIOCHARGE project looked at the large genus Enterococcus that is a normal inhabitant of the human and animal gut. There are more than 17 species, but E. faecalis and E. faecium most commonly cause infections in humans. It is generally accepted that acquiring antibiotic resistance leads to a loss of fitness in the bacterium. Focusing on the diversity of Tn916, the scientists looked at how carrying the element affects survival in 100 tetracycline-resistant strains, including 7 different strains of enterococci. The researchers used polymerase chain reaction to amplify Tn916-like cTns followed by restriction fragment length polymorphism analysis. Diversity of Tn916 was surprisingly low in the 100 strains originating from China, Denmark, England, Portugal, Spain, Sweden and the United States. In other genera such as oral Streptococcus, variation of these elements is much higher. Looking at growth rates of bacteria harbouring Tn916 and another in the same family, Tn6000, the scientists found a wide range of biological cost to the bacteria. For Tn6000, fitness cost was only around 3 %, but for Tn916 it was as high as 16.7 %. Further research revealed that when the bacteria first incorporate Tn916, the cost is really high — up to 46 %. However, after only 700 generations in the absence of tetracycline, the cost was lowered, which explains the high prevalence of Tn916 worldwide. Using a knock-out mutation, the researchers also found that stability of the resistance unit was consistently 100 %. BIOCHARGE results show that bacteria can adapt to the loss of biological fitness after the acquisition of resistance genes in a very short time. As the resistance genes remain stable in the gut bacterium Enterococcus, stopping widespread use of tetracycline is not likely to reduce incidence of this type of resistance.

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