Antibiotic resistance is a gut reaction


The bacteria produce compounds, called cephalosporinases, which inactivate and destroy certain antibiotics such as penicillin derivatives and cephalosporins, protecting themselves and other beneficial bacteria that live in close proximity. However, they may also give protection from these antibiotics to harmful bacteria, such as Salmonella.

The gut is home to hundreds of trillions of bacteria, which have important roles in maintaining our health. But a side effect of taking antibiotics is that these may also kill off some of our beneficial gut bacteria, allowing harmful bacteria to gain a foothold and cause an infection. Susceptibility to antibiotics isn’t uniform in the hundreds of species that colonise our guts, and some of the most common bacteria, the Bacteroides, are among the most resistant.

By scanning the genome of strains of Bacteroides bacteria that live in the gut, the researchers found genes that produce an enzyme called cephalospoprinase, which specifically destroys certain antibiotics. They also showed that the cephalosporinases are exported out of the bacterial cells, attached to the surface of special packages called outer membrane vesicles (OMVs).

Bacteria use OMVs to distribute compounds made inside the bacterial cells to the outside world. Among these packaged compounds are cephalosporinases that can help protect any other bacteria that are in the same environment against antibiotics such as ampicillin. This was shown by adding the cephalosporinase-containing OMVs to cultures containing the ampicillin-susceptible gut bacteria, Bifidobacteria breve, which effectively protected them against high concentrations of antibiotics. A similar test showed that Salmonella bacteria were also protected.

The research team at UEA included Dr Charles Brearley from the School of Biological Sciences, and Prof David Livermore and Prof Simon Carding, both from Norwich Medical School. The study was led by Dr Regis Stentz from IFR.

The research team now want to see whether the protection against antibiotics from gut bacteria OMVs occurs in the gut itself. If so, this would have implications for how we use antibiotics. It will also improve our understanding of the growing problem of antibiotic resistant bacteria.

‘Cephalosporinases associated with outer membrane vesicles released by Bacteroides spp. protect gut pathogens and commensals against {beta}-lactam antibiotics’ is published in the Journal of Antimicrobial Chemotherapy. The research was funded by the Biotechnology and Biological Sciences Research Council. 

Above: When treated with the antibiotic, the bacteria dramatically change shape, becoming filamentous. Images by Louise Salt and Kathryn Cross

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