A recent research paper in Science is a massive wake up call when it comes to the useage and development of new antibiotics. The paper, Sampling the Antibiotic Resistome by Vanessa M. D'Costa et al, demonstrates just how widespread the mechanisms that bacteria have to resist antibiotics actually are in the current environment. This is important because the origins of a lot of antibiotic resistance genes, such as those conferring resistance to vancomycin are believed to come from this "antibiotic resistome" or environmental reservoir. It is generally thought that these genes can pass from the environmental organisms to pathogens by horizontal gene transfer.
In the study, they examined actinomyces soil-dwelling spore forming bacteria such as Steptomyces against a wide range of antibiotics, 21 in total, including vancomycin and synthetic antibiotics such as ciprofloxacin. In total, a library of 480 strains was constructed and then screened for their resistance against the 21 antibiotics they had assembled. Although screened at high concentrations of each antibiotic, a disturbingly large number of bacteria were resistant and many even able to enzymatically destroy the antibiotics in question. Most of the bacteria were resistant to 6-8 different antibiotics and two strains were resistant to 15(!) of the 21 antibiotics tested.
Possibly the most disturbing finding of the paper was just how poorly some new medically important antibiotics performed against these isolates. Daptomycin, which is hoped to be a new front line drug for use on multi-drug resistant pathogens like MRSA, was found to be utterly ineffective against all strains with a whopping 80% being able to inactivate the drug. This is pretty significant because it indicates that resistance to some of our newer front line drugs are already out there and could potentially be passed to pathogens. Additionally, many other antibiotics that aren't even commonly encountered by soil microbes appeared to have resistance determinants already, such as fluoroquinolones and of course synthetic antibiotics like ciprofloxacin.
An interesting result from my perspective concerned the antibiotic rifampicin. Rifampicin is important in the treatment of mycobacterial infections and typically resistance only shows up through several point mutations in the targets RNA polymerase beta sub-unit. This study demonstrated that several of these soil microbes could actually break the antibiotic down completely and didn't require said point mutations. This could probably lend weight to the concept that mycobacteria in general don't tend to aquire resistance (or other genes for that matter) through horizontal gene transfer terribly often.
Overall, the findings of the paper show two incredibly disturbing trends. The first is just how much range of antibiotics soil bacteria can resist, and the wide array of mechanisms and mutations they have for doing so. The second is that many of the antibiotics we have used for years have high amounts of innate resistance in the soil microbiota and worse still, many new 'up and coming' antibiotics already face the threat of high resistance genes in the environment. Although the study didn't demonstrate how much of these determinants can spread between soil bacteria and clinically important organisms, such a large reservoir cannot be ignored as it is potentially an extremely high risk. Finally, the study was highly limited to only what bacteria could be grown in the lab and actually underestimates the actual amount of resistance present in the environment.
It's fairly clear from these sorts of findings that antibiotic use has to be heavily conserved and selection for the development or aquisition of resistance genes has to be carefully monitored. These genes are already out there in the environment and doing highly irresponsible things like feeding our antibiotics willy nilly to farm animals, is going to set up a time bomb for processes like horizontal gene transfer to work on.
