antibiotic resistance

By Ian Pepper, The University of Arizona

Published in Environ Sci. Technol. 2018 52:3949-3959

Microorganisms naturally produce and secrete antibiotic compounds, which can inhibit the growth of competing microbes in the environment. Due in part to their germicidal effects, antibiotics are useful as therapeutic agents for the control of infectious disease in humans and animals. However, the more that antibiotics are used for the treatment or prevention of disease, the greater the likelihood that resistant disease strains will occur. Antibiotic bacteria are commonly detected in biosolids, so I undertook a literature review to examine the question of whether biosolids might contribute to “environmental antibiotic resistance.” 

The first and perhaps most effective antibiotic discovered was penicillin, serendipitously isolated from the soil fungus Penicillium by Sir Alexander Fleming in 1929. A second major antibiotic, streptomycin, was later isolated from the soil actinomycete Streptomyces griseus, by the soil microbiologist Selman Waksman in 1943. Waksman received the Nobel Prize for this discovery in 1952 - the only soil scientist to ever achieve such an honor. These powerful antibiotics revolutionized our ability to treat infectious diseases, but not without a concomitant cost.

Bacteria are simple prokaryotic microbes that can metabolize and replicate very quickly, resulting in remarkable genetic plasticity and adaptability. The existence of only one bacterial cell with a genetic or mutational change that confers resistance to an antibiotic agent encountered in the environment is sufficient for the subsequent proliferation of antibiotic resistant bacteria (ARB) that contain antibiotic resistant genes (ARG). ARGs are now considered to be a class of emerging contaminants.  Thus, the more that antibiotics are used for the treatment or prevention of disease, the greater the likelihood that resistant strains will occur due to the selective advantages conferred by ARG. More specifically, the potential for the transfer of antibiotic resistance to human pathogenic microbes that subsequently can no longer be controlled by the prescribed antibiotics is of paramount concern. The conundrum then, is the more an antibiotic is utilized to prevent infectious disease, the less effective it will become over time. In addition, public health risks increase significantly when bacteria accumulate resistance to multiple antibiotics, making them particularly difficult to control as in the case of methicillin-resistant Staphylococcus aureus (MRSA). CDC estimates of antibiotic resistant infections are a minimum of 2 million people in the United States annually resulting in 23,000 deaths. 

ARB and ARG are commonly detected in domestic wastewater, agricultural waste releases from concentrated animal feedlot operations (CAFOs), biosolids and animal manures, hospital waste discharged into sewers, and soil and water.  The role of anthropogenic activity on the incidence of ARB and ARG led to the introduction of the term “environmental antibiotic resistance,”  as well as several review articles including “The Scourge of Antibiotic Resistance; The Important Role of the Environment,” and “Urban Wastewater Treatment Plants as Hotspots for Antibiotic Resistant Bacteria and Genes Spread into the Environment: A Review”.  

However, the vast majority of antibiotics are natural products synthesized by soil microorganisms. All soils, even pristine soils, contain antibiotics and antibiotic resistant bacteria. Even more stunning is documentation that antibiotic resistance in soils existed on earth over a billion years ago. By using data from the literature it can be shown that in an acre, there are ≃ 1016 antibiotic resistant bacteria in the soil. Again using data from the literature, it can be shown that land application of 2 tons of biosolids to that acre only increases the number of ARBs by ≃ 0.1%. Therefore it is not surprising that a number of studies have shown that land application of biosolids results in no significant increase in ARBs. 

Based on inputs of ARBs from land application of biosolids, relative to the numbers of ARBs that were already in the soil, it can be concluded that the vast majority of antibiotic resistance in soil is due to natural phenomena that has been present for millions or even billions of years, and not land application.