Team:Peking R/HumanPractice

  Review of Antibiotic Use and Potential Harms

Since their discovery, antibiotics have been considered as the primary solution to most infectious diseases and have saved billions of lives. However, the abuse of antibiotics, combined with the widespread use of antibiotic resistance genes as selection markers, have lead to a worldwide hazard to public health - bacterial antibiotic resistance. It has become much easier to find antibiotic-resistant bacteria around us[1]. Increasing reports regarding superbugs - bacteria that are resistant to most common antibiotics - is also raising public concern. They have posed great threats to public health by increasing the possibilities of infectious disease outbreaks, such as the recent E.coli outbreak in Europe a few months ago. E.U. has reported 25,000 deaths caused by bacterial infection, which has even outsmarted newly invented antibiotics[2]. (See http://blogs.nature.com/news/2011/06/europes_e_coli_out-break_time_f.html for a full version of the report) It is widely believed that the abuse of antibiotics accounts for the spread of antibiotic-resistant bacteria. However, the fact that laboratory work also significantly contributes to this process cannot be ignored. Our Human Practice focuses on the treatment of used or excessive antibiotic-resistant bacteria, and discusses feasible precautions against the spread of antibiotic-resistant microbes.

Inappropriate use of antibiotics is a major cause of bacterial antibiotic resistance. The public used to depend on antibiotics to treat infections regardless of whether they are of viral origins or may be treated by means other than antibiotics. To make matters worse, in many countries, the public has access to antibiotics without prescriptions. As the public does not strictly follow instructions at all times, bacterial antibiotic resistance is further aggravated. The challenge in confronting antibiotic resistance lies in the possibility that even if antibiotic use is reduced, resistant clones would remain persistent and cannot be rapidly outcompeted by their susceptible relatives[3].

Besides treatment of infections, antibiotics are also widely used in agriculture, where they are added to food for animals to prevent infectious diseases and promote growth. It is relatively more difficult for the public, however, to establish the correlation between antibiotic use on farm animals and potential hazards to public health. Despite the lack of statistical data confirming the scale of antibiotic use, it is reasonable to estimate that the majority of antibiotics and related products are used in agriculture for their cheapness and safety to livestock. Besides, it is also unlikely that farmers will carefully control the dosage of antibiotics applied to animals. Consequentially, excessive amounts of antibiotics selects for bacteria with stronger resistance, and the related genes may be transferred to other microbes through horizontal gene transfer[4], which may then pose greater challenges to biosafety.
One of the primary goals of synthetic biology is to render the design of biological systems easier for more researchers to take part in the design process. Great efforts have been made to develop toolkits which are easy and convenient for users without professional backgrounds in biology[5]. The extensive use of such toolboxes has attracted researchers from other disciplines such as engineering and computer sciences, contributing cross-disciplinary skills and techniques to conventional biological sciences. However, the participation of researchers lacking systematic training in biosafety inevitably increases the risk of biohazards, including:

1. High possibility that in the near future organizations of non-research origins will be able to  produce recombinant or mutant species in a large scale, probably threatening the environment and public safety.
2. Improper treatment of microbes and corresponding DNA fragments in the laboratory by researchers unaware of biosafety.

Researchers, being too familiar with antibiotic-resistant bacteria to treat them with caution, may also negatively affect public safety even if they have indeed undergone professional training in biosafety. Common treatments, such as pouring solutions or medium containing microbes into the sewer or throwing them into garbage cans, may expose antibiotic-resistant bacteria to the environment, increasing the risk of transferring antibiotic-resistant genes to wildtype microbes. A more subtle form of risk is the ever wider application of Polymerase Chain Reaction(PCR), which allows microbial DNA fragments to be rapidly replicated and promotes formation of mutant or recombinant DNA via error-prone replication[6].

reference:

[1]1. Livermore, D.M. Has the era of untreatable infections arrived? J. Antimicrob. Chemother 64 (suppl 1), i29–36 (2009).
[2]. As E. coli Outbreak Recedes, New Questions Come to the Fore. Science 333, 27 (2011).
[3]. Andersson, D.I., and Hughes, D., Persistence of antibiotic resistance in bacterial populations. FEMS Microbiol Rev(2011).­(Accepted Article)
[4]. Wiedenbeck, J., and Cohan, F.M., Origins of Bacterial Diversity through Horizontal Genetic Transfer and Adaptation to New Ecological Niches. FEMS Microbiol Rev(2011).­(Accepted Article)
[5]. Schmidt, M., Diffusion of synthetic biology: a challenge to biosafety. Syst Synth Biol 2, 1–6 (2008).
[6]. Bügl, H., Danner, J.P., Molinari, R.J., Mulligan, J.T., Park, H., Bas Reichert, Roth, D.A., Wagner, R., Budowle, B., Scripp, R.M., Smith, J.A.L., Steele, S.J., Church, G., and Endy, D., DNA Synthesis and Biological Security. Nat Biotech 25, 627-629 (2007).