Antibiotic Growth Promoters: A Double-edged Sword of Antibiotic Resistance and Virulence

Food Tank had the opportunity to interview Dr. Byeonghwa Jeon about foodborne pathogens and antibiotic resistance.

Dr. Byeonghwa Jeon is an assistant professor in the School of Public Health at the University of Alberta in Canada. He teaches courses on Food Safety and One Health, and his research focuses on foodborne pathogens and antibiotic resistance. Dr. Jeon has written numerous articles on food safety and antibiotic resistant bacteria.


Recently we  had the opportunity to speak with Dr. Jeon about his work in food safety and his most recent study on antibiotic growth promoters and the emergence of pathogenic E. coli.
  
Can you talk about how you became interested in food safety and food-borne pathogens?
Byeonghwa Jeon (BJ): When I was studying food science and biotechnology as a masters student in Sweden, my mother suddenly passed away. After that heartbreaking incident, I seriously considered switching my career to medicine, but, rather, I chose to study such an area in food science that is directly related to human health. That area was food safety.

How are foodborne illnesses spread?
BJ: It sounds simple, as it says ‘foodborne,’ but is quite a difficult question. The spread of foodborne illnesses may occur at every step during food production: processing, distribution, and even consumption. To understand the spread of foodborne illnesses, a holistic understanding of the whole ecology surrounding food production is required. Since most major foodborne pathogens are of animal origin, such as E. coli O157:H7 in cattle and Campylobacter in poultry, the dissemination of the pathogens from animals to animals or from the environment to animals may first start on farms. Fecal discharge of these intestinal pathogens from the host animals to soil and water may affect the production of safe, fresh produce. Proper maintenance of food hygiene during the downstream processing affects the spread of foodborne pathogens. Of course, food handlers in kitchens also play an important role in the spread of foodborne pathogens. Since numerous factors and sources affect food safety from food production to consumption, we often say food safety from farm to table (or fork) and researchers endeavor to understand food safety from the perspective of One Health, which is an integrated approach to understanding human health in connection with animals and the environment.

How many people suffer from food-related illnesses annually? 
BJ: According to a recent report from the World Health Organization, approximately two billion infection cases are estimated to occur around the world per year.

What techniques and strategies can individuals utilize to mitigate the risks of food-borne illnesses?
BJ: Although there are many risk factors that are beyond the control of individuals, each person can manage to “cook properly and store appropriately." It may sound like a mom’s everyday nag to “brush your teeth,” but often, something important may start from something simple and basic.
  
The Centers for Disease Control and Prevention (CDC) in the U.S. reported that 22 percent of human infections with antibiotic-resistant pathogens are associated with foodborne hazards. How does the increasing prevalence of antibiotic-resistant foodborne pathogens affect public health?
BJ: The significance of this report is far beyond the number of “22 percent,” in comparison with 78 percent that is related to something else other than foods. As I mentioned earlier, major foodborne pathogens are originated from animals. Therefore, antibiotic-resistant foodborne pathogens are mostly from animals that carry antibiotic resistance. If you were to consider food production systems in the United States, only a minor portion of foods would be contaminated by pathogens. The "minor" constitutes the 22 percent of resistant infections. The majority of antibiotic-resistant foodborne pathogens, which mostly inhabit the intestines of food-producing animals, is released to the environment. If you imagine the big picture, it would only be a matter of time before food-producing animals and the environment might be saturated with resistant pathogens in the future, even though I wish such a thing will never happen.

Let me share a gruesome finding of Doctors Wang and Shen at China Agricultural University (co-authors of our Emerging Infectious Diseases paper). Colistin is one of the last resort antimicrobials to treat dangerous resistant pathogens. They demonstrated that colistin resistance has been spread from animals to humans. This finding was recently published in Lancet Infectious Diseases. We should take some serious steps to stop the spread of resistant pathogens in foods, animals, and the environment because human health and life is subject to all of them.

You and your colleagues recently published a study showing that antibiotic growth promoters may not only affect the development of antibiotic resistance but also the emergence of pathogenic E. coli, a serious threat to food safety. Can you explain how this novel finding may affect food safety?
BJ: Public health concerns about antibiotic growth promoters are primarily about antibiotic resistance. Our recent publication in Emerging Infectious Diseases revealed a completely different, but important, problem of antibiotic growth promoters. To help understand, let me provide a brief explanation. E. coli O157:H7 is a notorious foodborne pathogen worldwide. Its most important virulence factor is Shiga toxin (Stx). Genes responsible for the production of Stx are encoded by bacteriophages, viruses that infect only bacteria, not humans. When the host bacteria harboring a Stx-encoding phage are healthy, the phage parasitically hides in the DNA of the bacteria cell. However, when the host bacteria are stressed or endangered, such as by antibiotic treatment, the phage starts to multiply in number within the bacterial cell and burst out of it. Due to this problem, antibiotic treatment is not recommended in human patients infected with E. coli O157:H7, because antibiotic treatment may increase the number of Stx-encoding phages; increasing the production of Stx and causing serious patient outcomes.

Cattle are the major natural reservoirs for E. coli O157:H7; thus, antibiotics will increase the number of Stx-encoding phages in cattle. Fortunately for cattle, they are not affected by Stx at all; however, there is a different problem in cattle. Stx-encoding phages are kinds of viruses, and they are contagious and infect non-pathogenic E. coli. The Stx-encoding phage transfer may convert non-pathogenic E. coli to Stx-producing, pathogenic E. coli. The study showed that antibiotic growth promoters may facilitate dissemination of the most dangerous virulence gene (Shiga toxin gene) of E. coli O157:H7 to non-pathogenic E. coli. In addition to E. coli O157:H7, a wide range of different E. coli strains has been reported to produce Stx, and the United States Department of Agriculture (USDA) has also strengthened the safety regulations about non-O157 Stx-producing E. coli, such as E. coli O26, O103, O45, O111, O121 and O145 (what is called "Bix Six"). Our study suggested that bovine antibiotic growth promoters would be implicated in the expansion of Stx-producing E. coli. Another important finding in the study is that oxytetracycline and chlortetracycline, antibiotics commonly used in agriculture, significantly stimulated the expansion of Stx-producing E. coli even at substantially low concentrations. Since antibiotics may affect the emergence of new pathogenic E. coli strains, the findings would have a significant impact on food safety associated with Shiga toxin-producing E. coli.

What else should Food Tank readers know about antibiotic-resistance and foodborne pathogens?
BJ: This is a too broad question to answer, but let me bring one thing to your attention. We are usually cautious in handling meat products due to microbial contamination, but fresh produce is the primary cause of foodborne illnesses in the United States. The contamination of fresh produce may occur at the pre-harvest level, and in most cases, it is difficult to control the safety of fresh produce at the level of consumers without changing cooking styles, such as steaming vegetables for Chinese foods. Nevertheless, it is still helpful to be aware of the risks. In particular, if the consumers are children and the elderly, please avoid eating raw bean sprouts. I wish all of you will stay healthy!