ReviewEnvironmental pollution by antibiotics and by antibiotic resistance determinants
Introduction
Antibiotics are probably the most successful family of drugs so far developed for improving human health. Besides this fundamental application, antibiotics (antimicrobials at large) have also been used for preventing and treating animals and plants infections as well as for promoting growth in animal farming (McManus et al., 2002, Smith et al., 2002, Singer et al., 2003, Cabello, 2006). All these applications made antibiotics to be released in large amounts in natural ecosystems. Little is known on the overall effects of antibiotics on the population dynamics of the microbiosphere (Sarmah et al., 2006). However, the effect of antibiotics used for treating infections or for farming purposes in the selection of antibiotic-resistant microorganisms, which can impact human health has been studied in more detail (Witte, 1998, Ferber, 2003, Singer et al., 2003). As stated by the World Health Organization, the increasing emergence of antibiotic resistance in human pathogens is a special concern, not only for treating infectious disease, but also for other pathologies in which antibiotic prophylaxis is needed for avoiding associated infections. In this regard, the spread of antibiotic-resistant bacteria “…means that commonplace medical procedures once previously taken for granted could be conceivably consigned to medical limbo. The repercussions are almost unimaginable” (WHO, 2000).
It is important to remark that several antibiotics are produced by environmental microorganisms (Waksman and Woodruff, 1940). Conversely, antibiotic resistance genes, acquired by pathogenic bacteria trough Horizontal Gene Transfer (HGT) have been originated as well in environmental bacteria (Davies, 1997), although they can evolve later on under strong antibiotic selective pressure during the treatment of infections (Martinez and Baquero, 2000, Martinez et al., 2007). To understand in full the development of resistance, we will thus need to address the study of antibiotics and their resistance genes, not just in clinics but in natural non-clinical environments also (Martinez, 2008). The situation concerning antibiotics and their resistances resembles in some aspects to heavy metal contamination. Like antibiotics, heavy metals are natural compounds present in different ecosystems. However, their utilization by humans has increased their bioavailability, leading to dramatic changes in polluted ecosystems. Differing to heavy metals that challenge all forms of life, antimicrobials mainly alter the microbiosphere and probably because of this, the consequences of antibiotic pollution on the biodiversity have received less attention.
Understanding heavy metal resistance in natural ecosystems may help as well to understand antibiotic resistance in the environment. The elements involved in the resistance to heavy metals are encoded in the chromosomes of bacteria like Ralstonia metallidurans (Mergeay et al., 2003), which are well adapted for surviving in naturally heavy metals-rich habitats (e.g. volcanic soils). However, strong selective pressure due to anthropogenic pollution has made that these chromosomally-encoded determinants are now present in gene-transfer units, so that they can efficiently spread among bacterial populations (Silver and Phung, 1996, Silver and Phung, 2005, Nies, 2003). Similarly, antibiotic resistance genes that were naturally present in the chromosomes of environmental bacteria (D'Acosta et al., 2006, Wright, 2007, Fajardo et al., 2008) are now present in plasmids that can be transferred to human pathogens. It has been highlighted that the contact of bacteria from human-associated microbiota with environmental microorganisms in sewage plants or in natural ecosystems is an important feature to understand the emergence of novel mechanisms of resistance in human pathogens (Baquero et al., 2008). A key issue for this emergence will be the integration of antibiotic resistance genes in gene-transfer elements (e.g. plasmids), a feature that is favoured by the release of antibiotics in natural ecosystems (Cattoir et al., 2008).
Section snippets
Functional role of antibiotics and antibiotic resistance elements in bacterial natural ecosystems
Since antibiotics are efficient inhibitors of bacterial growth produced by environmental microorganisms, it has been widely accepted that their role in nature will be to inhibit microbial competitors. Conversely, antibiotic resistance determinants should serve to avoid the activity of antibiotics, in such a way that they would be a good example of the Darwinian struggle for life. Although this can be true in some occasions, an alternative hypothesis stating that antibiotics could be signal
Different consequences of antibiotic pollution and antibiotic resistance pollution
Antibiotic utilization for clinical or farming purposes selects resistant microorganisms (Teuber, 2001, Livermore, 2005). It is thus predictable that residues from hospitals or farms will contain both types of pollutants: antibiotics and resistance genes. Nevertheless, the fate of both types of pollutants is likely different. Several antibiotics are natural compounds that have been in contact with environmental microbiota for millions of years and are thus biodegradable, an even serve as a food
Release, behaviour and effects of antibiotics in natural ecosystems
Most antibiotics used for preventing or treating infections in humans or animals as well as for promoting faster growth of livestock are only partially metabolized and are then discharged along the excreta, either to sewage treatment plants or straightforward in waters or soils (Dolliver and Gupta, 2008). Besides, antimicrobial compounds used in intensive fish farming are added directly to the water rendering high local concentrations both in water and in adjoining sediments (Cabello, 2006). In
When an antibiotic resistance gene is a pollutant
Several works highlight the presence of antibiotic resistance genes in pristine, isolated or extreme environments that are unlikely contaminated with antibiotics used by humans. These include the deep terrestrial subsurface (Brown and Balkwill, 2009), non-contaminated Antarctic waters (De Souza et al., 2006) or deep Greenland ice core (Miteva et al., 2004) among others. These works constitute a good example of the ubiquity of genes that might confer resistance upon expression in a heterologous
Mechanisms for the maintenance of antibiotic resistance genes
A key issue for predicting the fate of antibiotic resistance genes in natural environments is the understanding of their effects on bacterial physiology. It has been assumed that antibiotic resistance confers a metabolic burden for the resistant bacteria so that they will be out-competed by their wild-type counterparts in the absence of antibiotic selective pressure (Andersson and Levin, 1999, Andersson, 2006). Although in some occasions this is likely true, some examples demonstrate that
Consequences of pollution by antibiotic resistance genes
Pollution by antibiotic resistance genes can increase the chances of human pathogens for acquiring resistance. The release of residues containing human microbiota into environments containing bacteria enriched in resistance elements increases the possibility of acquiring novel resistance determinants by human-linked bacteria. For this reason, it has been proposed that the release of residues from hospitals that contain human commensal and infective bacteria (resistant and susceptible) as well
Concluding remarks
The release of high concentrations of antibiotics and resistance genes in natural ecosystems is a recent event in evolutionary terms. Nevertheless, both types of pollution can impact the structure and the activity of environmental microbial populations. Given that environmental microorganisms are the original source of resistance genes acquired through HGT by human pathogens (Davies, 1997), these changes are relevant for the future of human health. It has been reported that the same antibiotic
Acknowledgements
Author's laboratory is supported by grants BIO2005-04278 and BIO2008-00090 from the Spanish Ministerio de Ciencia e Innovación, and LSHM-CT-2005-518152 and LSHM-CT-2005-018705 from European Union. Thanks are given to Helen Green for language editing.
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