Dissemination of Antimicrobial Resistance in Microbial Ecosystems through Horizontal Gene Transfer

Urban wastewater treatment plants (UWTPs) are among the main sources of antibiotics' release into the environment. The occurrence of antibiotics may promote the selection of antibiotic resistance genes (ARGs) and antibiotic resistant bacteria (ARB), which shade health risks to humans and animals. In this paper the fate of ARB and ARGs in UWTPs, focusing on different processes/technologies (i.e., biological processes, advanced treatment technologies and disinfection), was critically reviewed. The mechanisms by which biological processes influence the development/selection of ARB and ARGs transfer are still poorly understood. Advanced treatment technologies and disinfection process are regarded as a major tool to control the spread of ARB into the environment. In spite of intense efforts made over the last years to bring solutions to control antibiotic resistance spread in the environment, there are still important gaps to fill in. In particular, it is important to: (i) improve risk assessment studies in order to allow accurate estimates about the maximal abundance of ARB in UWTPs effluents that would not pose risks for human and environmental health; (ii) understand the factors and mechanisms that drive antibiotic resistance maintenance and selection in wastewater habitats. The final objective is to implement wastewater treatment technologies capable of assuring the production of UWTPs effluents with an acceptable level of ARB. Copyright © 2013 Elsevier B.V. All rights reserved.

The large majority of antibiotics currently used for treating infections and the antibiotic resistance genes acquired by human pathogens each have an environmental origin. Recent work indicates that the function of these elements in their environmental reservoirs may be very distinct from the "weapon-shield" role they play in clinical settings. Changes in natural ecosystems, including the release of large amounts of antimicrobials, might alter the population dynamics of microorganisms, including selection of resistance, with consequences for human health that are difficult to predict.

Plasmids are key vectors of horizontal gene transfer and essential genetic engineering tools. They code for genes involved in many aspects of microbial biology, including detoxication, virulence, ecological interactions, and antibiotic resistance. While many studies have decorticated the mechanisms of mobility in model plasmids, the identification and characterization of plasmid mobility from genome data are unexplored. By reviewing the available data and literature, we established a computational protocol to identify and classify conjugation and mobilization genetic modules in 1,730 plasmids. This allowed the accurate classification of proteobacterial conjugative or mobilizable systems in a combination of four mating pair formation and six relaxase families. The available evidence suggests that half of the plasmids are nonmobilizable and that half of the remaining plasmids are conjugative. Some conjugative systems are much more abundant than others and preferably associated with some clades or plasmid sizes. Most very large plasmids are nonmobilizable, with evidence of ongoing domestication into secondary chromosomes. The evolution of conjugation elements shows ancient divergence between mobility systems, with relaxases and type IV coupling proteins (T4CPs) often following separate paths from type IV secretion systems. Phylogenetic patterns of mobility proteins are consistent with the phylogeny of the host prokaryotes, suggesting that plasmid mobility is in general circumscribed within large clades. Our survey suggests the existence of unsuspected new relaxases in archaea and new conjugation systems in cyanobacteria and actinobacteria. Few genes, e.g., T4CPs, relaxases, and VirB4, are at the core of plasmid conjugation, and together with accessory genes, they have evolved into specific systems adapted to specific physiological and ecological contexts.