The World Health Organization (WHO) recently published a report on the dramatic increase of antibiotic resistances in bacteria around the world, stating that “A post-antibiotic era – in which common infections and minor injuries can kill – far from being an apocalyptic fantasy, is instead a very real possibility for the 21st Century”(1). Antibiotic resistances have serious medicinal and financial consequences. According to the Centres for Disease Control, approximately 70% of all people with bacterial infections in hospitals in the Unites(2) or 1.4 million people get bacterial infections that are resistant to at least one prevalently used antibiotic in hospitals in the United States every year. Furthermore, the National Academy of Science estimates an increase of $4 billion in healthcare costs every year in the United States associated with antibiotic resistant bacteria(2).

How do these antibiotic resistances develop? When bacteria are constantly exposed to high levels of antibiotics, they try to develop a defence mechanism against these antibiotics by taking in extracellular parts and even mutating their own DNA to produce an “anti antibacterial protein,” that disrupts the function of the antibiotics by either binding to it or degrading it. Those bacteria that are successful in warding off the antibiotics replicate through natural selection and are said to have an antibiotic resistance.

Lately the concentration of antibiotics in the water system, that would cause bacteria to develop antibiotic resistances, has been rising. One of the main ways antibiotics enter the water system is from run-off from feedlots. Antibiotics are fed to 83% of cattle feedlots and 84% of sheep farms in the United States in order to promote growth(3). Additionally, an estimated 75% of all antibiotics fed to animals are not fully digested and will eventually enter the environment(2).

A class of antibiotics that are commonly found in the water is penicillin. Penicillin is distinguished by its beta-lactam ring, which is a cyclic, 4-part amide ring attached to a carbonyl group, that prevents cell wall formation and thus kills the bacteria(4). In response to penicillin, the bacteria will produce the enzyme beta-lactamase, which degrades the beta-lactam ring in penicillin using hydrolysis (5).

1. WHO report on antimicrobial resistance

2. Antibiotics and the Food Animal Industry

3. Preventing Antibiotic Resistance Act of 2013

4. Lactam

5. Siddheshwar, S.S et al (2013). Need and Scope of Development of β-lactums

The Lethbridge HS iGEM team is attempting to find a solution to tackle the global issue of increased antibiotic resistances in bacteria by focusing on reducing the levels of antibiotics, primarily penicillin, in the water system. To do this, we are having E-coli excrete beta-lactamase into its periplasmic space. Once the penicillin and the E-coli meet, and the pencillin enters into the E-coli's periplasmic space, the beta-lactamase will degrade the penicillin. This way the overall concentration of antibiotics in the water will start to decrease. Furthermore, we would like to characterize these signal sequences with other antibacterial resistance genes in order to have E-coli excrete other proteins, such as erythromycin esterase A, that would target a different class of antibiotics and therefore make our construct more effective. We hope to be able to apply our construct in a water treatment plant in the form of a bioreactor in order to decrease the levels of penicillin in the water system and limit the amount of time the bacteria will have to adapt to the stressed, antibiotic-rich environment.