Antimicrobial resistance – which most people hear about as antibiotic resistance – is a type of drug resistance where a microorganism is able to survive exposure to the medicine meant to treat it. Standard treatments become ineffective, and infections persist and sometimes spread. In aquaculture, the farmed fish often receive large doses of antibiotics to protect them from disease, and today there are many publications investigating antimicrobial resistance and aquaculture. Keith Hayse-Gregson spoke to Felipe Cabello of New York Medical College – who has published papers in this area – about this issue.
You’ve worked in the area of antimicrobial resistance in salmon aquaculture. How did you get interested in it?
My interest in the use of antimicrobials in salmon aquaculture was the result of becoming aware that in Chile – the second largest producer of farmed salmon in the world after Norway – the industry uses hundreds of metric tons of antimicrobials each year, including quinolones, florfenicol and tetracyclines.
The use of these large amounts of antimicrobials by this industry dwarfs their use in human medicine and other veterinary activities in Chile. It constitutes a powerful selective pressure for antimicrobial resistant bacteria and antimicrobial resistance genes in the environment.
This injudicious use of antimicrobials needs to be corrected and aquaculturists educated regarding the potential problems that this use has for animal and human health and for the environment.
Can the use of antimicrobial drugs in animal food production hinder the treatment of infections in humans?
Initially, people did not believe that using antimicrobial drugs in animal food production could hinder the treatment of infections in humans.
However, some bacteria are zoonotic. That means they can infect humans as well as other animal species. In the late 1960s, English scientists first realized that using antimicrobials in cattle production was causing an increase in antimicrobial resistant salmonella that could infect humans.
For many years people did not want to believe that antimicrobial resistance selected in animals could find its way into human pathogens. With time, it has become clear that not only have some antimicrobial resistant human pathogens originated in animals, but have also gotten their antimicrobial resistant genes from animal pathogens.
For example, it is now accepted that Staphylococcus aureus resistant to semi-synthetic penicillins possibly acquired the gene for this resistance from S. sciuri an animal pathogen. Another example of such a phenomenon is that resistant Campylobacter, a human pathogen, have been shown to originate in industrially farmed chickens.
What about drug resistance from aquaculture? Fish are not mammals and so how could antimicrobial resistance in aquatic bacteria and fish pathogens affect humans?
It’s true that, at first, it seems unlikely that antimicrobial resistant aquatic bacteria and fish pathogens – which exist in aquatic environments and in cold blooded animals – could impact human pathogens living in warm blooded organisms.
No one doubts that when antibiotics are used in aquaculture, the facilities and their surrounding environment harbor antimicrobial resistant bacteria and fish pathogens selected by this antibiotic use. The question is, can this impact human health? Many studies have found that antimicrobial resistance genes and genetic elements from bacteria in the aquatic environment can be shared by terrestrial bacteria including human pathogens.
Human pathogens, fish pathogens, and microbial communities in general are in more genetic contact than once believed. Scientists are discovering that microbes can share genetic material even between unrelated species by a process called horizontal gene transfer. It is hard for many people to believe that bacteria living in environments that are as distinct as the human gut and a fishpond can possibly exchange genetic material. The reality is that these exchanges do occur.
For example, a fish pathogen, Yersinia ruckerii, shares similar antimicrobial resistance genes with bacteria that produce bubonic plague in humans. Additionally, some quinolone resistance genes are beginning to emerge in human pathogens that appear to have originated in aquatic bacteria such as Shewanella, Aeromonas and Vibrio.
Unlike more advanced organisms, it seems that bacteria have access to a mobile pool of genetic material including antimicrobial resistance genes, which they share with one another. Scientists are finding that antimicrobial resistance can develop almost anywhere from the intestine of animals, including fish and humans, to free-living bacteria in the environment. Few obstacles block genetic transfer of these antimicrobial resistance elements between different bacterial species, especially in the presence of environmental antimicrobials as is the case in the aquatic environment of aquaculture facilities.
How long do antimicrobials persist in the environment?
Antimicrobials can persist in the environment for months or years. This means that scientists have no way of knowing when their selective effects will be exerted. A recent concept called, the resistome, indicates that antimicrobial resistance genes are present in bacteria in the whole biosphere and may potentially find their way into animal and human pathogens via the mobility of bacterial genes and genetic elements by horizontal gene transfer.
It must be noted that it will be difficult to prove directly that antimicrobial use in aquaculture directly influences the appearance of antimicrobial resistance in human pathogens since the pathways of horizontal gene transfer between aquatic bacteria and terrestrial bacteria are complex and may involve many intermediary species.
These two factors may leave a faint trail for scientists to follow and science may never uncover the smoking gun linking antimicrobial use in an aquaculture facility to antimicrobial resistance in human pathogens. However, this link has been confirmed repeatedly for terrestrial animals and it may be just a matter of time and effort before links between bacteria from aquaculture environments and human pathogens are firmly established.
How does industry need to adapt to prevent resistance occurring?
First, hygienic conditions of fish can be improved by stocking fish at lower densities to diminish stress and increase fish immune system strength. The space between cages and farms can also be increased so that diseases cannot spread quickly between cages or facilities.
Vaccinating juvenile fish before they are put into cages lowers the chance of disease outbreaks and reduces antimicrobial use.
Lastly, good veterinary and epidemiological management of antimicrobial use is required.
Norway is a good example of an aquaculture industry that has reduced antimicrobial use by improving aquaculture practices. In Norway, regulatory officials collect data on antimicrobial use and can use this data to predict how and where diseases will emerge and spread and to track them epidemiologically. They are then able to inform other aquaculturists so that the outbreak can be contained with minimal environmental and economic costs and without excessive therapeutic and prophylactic antimicrobial use.
James S. Diana is Director of the Michigan Sea Grant College Program and Professor of Fisheries and Aquaculture at the School of Natural Resources and Environment (SNRE) at University of Michigan. He and his students, including Keith Hayse-Gregson, are studying ecology of fishes as well as aquaculture. They have developed interests in aquaculture’s potential contribution to the global food supply through the understanding of ecologically sensitive aquaculture practices, particularly in developing countries. They also study a variety of natural ecosystems, focusing mainly on native species, particularly pike and muskellunge. Dr. Diana has studied the behavior and ecology of temperate fishes for three decades, working extensively on the behavior and ecology of many temperate fishes, including pike, muskellunge, brown trout, lake sturgeon, yellow perch, largemouth bass, and alewives. Keith Hayse-Gregson is a second-year MS student at SNRE, who recently conducted a study of the environmental impacts of a new freshwater aquaculture cage design in China.