Mathematical modelling of antimicrobial resistance in agricultural waste highlights importance of gene transfer rate. - Related Documents




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397901.0000Mathematical modelling of antimicrobial resistance in agricultural waste highlights importance of gene transfer rate. Antimicrobial resistance is of global concern. Most antimicrobial use is in agriculture; manures and slurry are especially important because they contain a mix of bacteria, including potential pathogens, antimicrobial resistance genes and antimicrobials. In many countries, manures and slurry are stored, especially over winter, before spreading onto fields as organic fertilizer. Thus, these are a potential location for gene exchange and selection for resistance. We develop and analyse a mathematical model to quantify the spread of antimicrobial resistance in stored agricultural waste. We use parameters from a slurry tank on a UK dairy farm as an exemplar. We show that the spread of resistance depends in a subtle way on the rates of gene transfer and antibiotic inflow. If the gene transfer rate is high, then its reduction controls resistance, while cutting antibiotic inflow has little impact. If the gene transfer rate is low, then reducing antibiotic inflow controls resistance. Reducing length of storage can also control spread of resistance. Bacterial growth rate, fitness costs of carrying antimicrobial resistance and proportion of resistant bacteria in animal faeces have little impact on spread of resistance. Therefore, effective treatment strategies depend critically on knowledge of gene transfer rates.201626906100
399210.9999Resistance in the environment. Antibiotics, disinfectants and bacteria resistant to them have been detected in environmental compartments such as waste water, surface water, ground water, sediments and soils. Antibiotics are released into the environment after their use in medicine, veterinary medicine and their employment as growth promoters in animal husbandry, fish farming and other fields. There is increasing concern about the growing resistance of pathogenic bacteria in the environment, and their ecotoxic effects. Increasingly, antibiotic resistance is seen as an ecological problem. This includes both the ecology of resistance genes and that of the resistant bacteria themselves. Little is known about the effects of subinhibitory concentrations of antibiotics and disinfectants on environmental bacteria, especially with respect to resistance. According to the present state of our knowledge, the impact on the frequency of resistance transfer by antibacterials present in the environment is questionable. The input of resistant bacteria into the environment seems to be an important source of resistance in the environment. The possible impact of resistant bacteria on the environment is not yet known. Further research into these issues is warranted.200415215223
647920.9999Fate and transport of antibiotic residues and antibiotic resistance genes following land application of manure waste. Antibiotics are used in animal livestock production for therapeutic treatment of disease and at subtherapeutic levels for growth promotion and improvement of feed efficiency. It is estimated that approximately 75% of antibiotics are not absorbed by animals and are excreted in waste. Antibiotic resistance selection occurs among gastrointestinal bacteria, which are also excreted in manure and stored in waste holding systems. Land application of animal waste is a common disposal method used in the United States and is a means for environmental entry of both antibiotics and genetic resistance determinants. Concerns for bacterial resistance gene selection and dissemination of resistance genes have prompted interest about the concentrations and biological activity of drug residues and break-down metabolites, and their fate and transport. Fecal bacteria can survive for weeks to months in the environment, depending on species and temperature, however, genetic elements can persist regardless of cell viability. Phylogenetic analyses indicate antibiotic resistance genes have evolved, although some genes have been maintained in bacteria before the modern antibiotic era. Quantitative measurements of drug residues and levels of resistance genes are needed, in addition to understanding the environmental mechanisms of genetic selection, gene acquisition, and the spatiotemporal dynamics of these resistance genes and their bacterial hosts. This review article discusses an accumulation of findings that address aspects of the fate, transport, and persistence of antibiotics and antibiotic resistance genes in natural environments, with emphasis on mechanisms pertaining to soil environments following land application of animal waste effluent.200919398507
399330.9999Environmental dissemination of antibiotic resistance genes and correlation to anthropogenic contamination with antibiotics. Antibiotic resistance is a growing problem which threatens modern healthcare globally. Resistance has traditionally been viewed as a clinical problem, but recently non-clinical environments have been highlighted as an important factor in the dissemination of antibiotic resistance genes (ARGs). Horizontal gene transfer (HGT) events are likely to be common in aquatic environments; integrons in particular are well suited for mediating environmental dissemination of ARGs. A growing body of evidence suggests that ARGs are ubiquitous in natural environments. Particularly, elevated levels of ARGs and integrons in aquatic environments are correlated to proximity to anthropogenic activities. The source of this increase is likely to be routine discharge of antibiotics and resistance genes, for example, via wastewater or run-off from livestock facilities and agriculture. While very high levels of antibiotic contamination are likely to select for resistant bacteria directly, the role of sub-inhibitory concentrations of antibiotics in environmental antibiotic resistance dissemination remains unclear. In vitro studies have shown that low levels of antibiotics can select for resistant mutants and also facilitate HGT, indicating the need for caution. Overall, it is becoming increasingly clear that the environment plays an important role in dissemination of antibiotic resistance; further studies are needed to elucidate key aspects of this process. Importantly, the levels of environmental antibiotic contamination at which resistant bacteria are selected for and HGT is facilitated at should be determined. This would enable better risk analyses and facilitate measures for preventing dissemination and development of antibiotic resistance in the environment.201526356096
398940.9999Antibiotic-Resistant Bacteria in Aquaculture and Climate Change: A Challenge for Health in the Mediterranean Area. Aquaculture is the productive activity that will play a crucial role in the challenges of the millennium, such as the need for proteins that support humans and the respect for the environment. Aquaculture is an important economic activity in the Mediterranean basin. A great impact is presented, however, by aquaculture practices as they involve the use of antibiotics for treatment and prophylaxis. As a consequence of the use of antibiotics in aquaculture, antibiotic resistance is induced in the surrounding bacteria in the column water, sediment, and fish-associated bacterial strains. Through horizontal gene transfer, bacteria can diffuse antibiotic-resistance genes and mobile resistance genes further spreading genetic determinants. Once triggered, antibiotic resistance easily spreads among aquatic microbial communities and, from there, can reach human pathogenic bacteria, making vain the use of antibiotics for human health. Climate change claims a significant role in this context, as rising temperatures can affect cell physiology in bacteria in the same way as antibiotics, causing antibiotic resistance to begin with. The Mediterranean Sea represents a 'hot spot' in terms of climate change and aspects of antibiotic resistance in aquaculture in this area can be significantly amplified, thus increasing threats to human health. Practices must be adopted to counteract negative impacts on human health, with a reduction in the use of antibiotics as a pivotal point. In the meantime, it is necessary to act against climate change by reducing anthropogenic impacts, for example by reducing CO(2) emissions into the atmosphere. The One Health type approach, which involves the intervention of different skills, such as veterinary, ecology, and medicine in compliance with the principles of sustainability, is necessary and strongly recommended to face these important challenges for human and animal health, and for environmental safety in the Mediterranean area.202134073520
648750.9999An evaluation of conventional and nature-based technologies for controlling antibiotic-resistant bacteria and antibiotic-resistant genes in wastewater treatment plants. Antibiotic resistance is a globally recognized health concern which leads to longer hospital stays, increased morbidity, increased mortality, and higher medical costs. Understanding how antibiotic resistance persists and exchanges in environmental systems like soil, water, and wastewater are critically important for understanding the emergence of pathogens with new resistance profiles and the subsequent exposure of people who indirectly/directly come in contact with these pathogens. There are concerns about the widespread application of prophylactic antibiotics in the clinical and agriculture sectors, as well as chemicals/detergents used in food and manufacturing industries, especially the quaternary ammonium compounds which have been found responsible for the generation of resistant genes in water and soil. The rates of horizontal gene transfer increase where there is a lack of proper water/wastewater infrastructure, high antibiotic manufacturing industries, or endpoint users - such as hospitals and intensive agriculture. Conventional wastewater treatment technologies are often inefficient in the reduction of ARB/ARGs and provide the perfect combination of conditions for the development of antibiotic resistance. The wastewater discharged from municipal facilities may therefore be enriched with bacterial communities/pathogens and provide a suitable environment (due to the presence of nutrients and other pollutants) to enhance the transfer of antibiotic resistance. However, facilities with tertiary treatment (either traditional/emerging technologies) provide higher rates of reduction. This review provides a synthesis of the current understanding of wastewater treatment and antibiotic resistance, examining the drivers that may accelerate their possible transmission to a different environment, and highlighting the need for tertiary technologies used in treatment plants for the reduction of resistant bacteria/genes.202438286289
398060.9999Antimicrobial resistance in dairy slurry tanks: A critical point for measurement and control. Waste from dairy production is one of the largest sources of contamination from antimicrobial resistant bacteria (ARB) and genes (ARGs) in many parts of the world. However, studies to date do not provide necessary evidence to inform antimicrobial resistance (AMR) countermeasures. We undertook a detailed, interdisciplinary, longitudinal analysis of dairy slurry waste. The slurry contained a population of ARB and ARGs, with resistances to current, historical and never-used on-farm antibiotics; resistances were associated with Gram-negative and Gram-positive bacteria and mobile elements (ISEcp1, Tn916, Tn21-family transposons). Modelling and experimental work suggested that these populations are in dynamic equilibrium, with microbial death balanced by fresh input. Consequently, storing slurry without further waste input for at least 60 days was predicted to reduce ARB spread onto land, with > 99 % reduction in cephalosporin resistant Escherichia coli. The model also indicated that for farms with low antibiotic use, further reductions are unlikely to reduce AMR further. We conclude that the slurry tank is a critical point for measurement and control of AMR, and that actions to limit the spread of AMR from dairy waste should combine responsible antibiotic use, including low total quantity, avoidance of human critical antibiotics, and choosing antibiotics with shorter half-lives, coupled with appropriate slurry storage.202236122459
399070.9999Environmental pollution by antibiotics and by antibiotic resistance determinants. Antibiotics are among the most successful drugs used for human therapy. However, since they can challenge microbial populations, they must be considered as important pollutants as well. Besides being used for human therapy, antibiotics are extensively used for animal farming and for agricultural purposes. Residues from human environments and from farms may contain antibiotics and antibiotic resistance genes that can contaminate natural environments. The clearest consequence of antibiotic release in natural environments is the selection of resistant bacteria. The same resistance genes found at clinical settings are currently disseminated among pristine ecosystems without any record of antibiotic contamination. Nevertheless, the effect of antibiotics on the biosphere is wider than this and can impact the structure and activity of environmental microbiota. Along the article, we review the impact that pollution by antibiotics or by antibiotic resistance genes may have for both human health and for the evolution of environmental microbial populations.200919560847
646280.9999Human health implications of clinically relevant bacteria in wastewater habitats. The objective of this review is to reflect on the multiple roles of bacteria in wastewater habitats with particular emphasis on their harmful potential for human health. Indigenous bacteria promote a series of biochemical and metabolic transformations indispensable to achieve wastewater treatment. Some of these bacteria may be pathogenic or harbour antibiotic resistance or virulence genes harmful for human health. Several chemical contaminants (heavy metals, disinfectants and antibiotics) may select these bacteria or their genes. Worldwide studies show that treated wastewater contain antibiotic resistant bacteria or genes encoding virulence or antimicrobial resistance, evidencing that treatment processes may fail to remove efficiently these bio-pollutants. The contamination of the surrounding environment, such as rivers or lakes receiving such effluents, is also documented in several studies. The current state of the art suggests that only some of antibiotic resistance and virulence potential in wastewater is known. Moreover, wastewater habitats may favour the evolution and dissemination of new resistance and virulence genes and the emergence of new pathogens. For these reasons, additional research is needed in order to obtain a more detailed assessment of the long-term effects of wastewater discharges. In particular, it is important to measure the human and environmental health risks associated with wastewater reuse.201323508533
399190.9999Antibiotic resistant pathogenic bacteria and their resistance genes in bacterial biofilms. Biofilm-forming bacteria are ubiquitous in the environment and also include biofilm-forming pathogens. Environmental biofilms may form a reservoir for risk genes and may act as a challenge for human health. Examples of the health relevance of biofilms are the increase in antibiotic resistant bacteria hosted in biofilms in hospital and environment and consequently the interaction of these bacteria with human cells, e.g. in the immune system. Although data concerning the occurrence and spread of resistant bacteria within hospital care units are available, the fate of these bacteria in the environment and especially in the aquatic environment has barely been investigated. Once antibiotic resistant bacteria have entered the environment, a back coupling by ingestion or other possible entry into the host has to be prevented. Therefore a strategy to investigate paths of entry, accumulation and spread of resistant bacteria in environmental compartments has been developed using quantitative determination of genetic resistance determinants. Additionally a bacterial bioassay assessed bioeffectivity thresholds of low antibiotic concentrations. This approach enables an evaluation of the potential of contaminated waters to exert a selection pressure on bacterial communities and thus promote the persistence of resistant organisms. Completed with an indicator system for the identification of sources of multiresistant bacteria a concept for monitoring and evaluation of environmental compartments with respect to their potential of antibiotic resistance dissemination is suggested.200616705607
9631100.9999Mathematical model for the transport of fluoroquinolone and its resistant bacteria in aquatic environment. Development of antibiotic resistance in environmental bacteria is a direct threat to public health. Therefore, it becomes necessary to understand the fate and transport of antibiotic and its resistant bacteria. This paper presents a mathematical model for spatial and temporal transport of fluoroquinolone and its resistant bacteria in the aquatic environment of the river. The model includes state variables for organic matter, fluoroquinolone, heavy metals, and susceptible and resistant bacteria in the water column and sediment bed. Resistant gene is the factor which makes bacteria resistant to a particular antibiotic and is majorly carried on plasmids. Plasmid-mediated resistance genes are transferable between different bacterial species through conjugation (horizontal resistance transfer). This model includes plasmid dynamics between susceptible and resistant bacteria by considering the rate of horizontal resistance gene transfer among bacteria and the rate of losing resistance (segregation). The model describes processes which comprise of advection, dispersion, degradation, adsorption, diffusion, settling, resuspension, microbial growth, segregation, and transfer of resistance genes. The mathematical equations were solved by using numerical methods (implicit-explicit scheme) with appropriate boundary conditions. The development of the present model was motivated by the fact that the Musi River is heavily impacted by antibiotic pollution which led to the development of antibiotic resistance in its aquatic environment. The model was simulated for hypothetical pollution scenarios to predict the future conditions under various pollution management alternatives. The simulation results of the model for different cases show that the concentration of antibiotic, the concentration of organic matter, segregation rate, and horizontal transfer rate are the governing factors in the variation of population density of resistant bacteria. The treatment of effluents for antibiotics might be costly for the bulk drug manufacturing industries, but the guidelines can be made to reduce the organic matter which can limit the growth rate of microbes and reduce the total microbial population in the river. The reduction in antibiotic concentration can reduce the selection pressure on bacteria and can limit the population of resistant culture and its influence zone in the river stretch; however, complete removal of antibiotics may not result in complete elimination of antibiotic-resistant bacteria.201828780691
3994110.9999Environmental Biofilms as Reservoirs for Antimicrobial Resistance. Characterizing the response of microbial communities to a range of antibiotic concentrations is one of the strategies used to understand the impact of antibiotic resistance. Many studies have described the occurrence and prevalence of antibiotic resistance in microbial communities from reservoirs such as hospitals, sewage, and farm feedlots, where bacteria are often exposed to high and/or constant concentrations of antibiotics. Outside of these sources, antibiotics generally occur at lower, sub-minimum inhibitory concentrations (sub-MICs). The constant exposure to low concentrations of antibiotics may serve as a chemical "cue" that drives development of antibiotic resistance. Low concentrations of antibiotics have not yet been broadly described in reservoirs outside of the aforementioned environments, nor is the transfer and dissemination of antibiotic resistant bacteria and genes within natural microbial communities fully understood. This review will thus focus on low antibiotic-concentration environmental reservoirs and mechanisms that are important in the dissemination of antibiotic resistance to help identify key knowledge gaps concerning the environmental resistome.202134970233
3985120.9999The scourge of antibiotic resistance: the important role of the environment. Antibiotic resistance and associated genes are ubiquitous and ancient, with most genes that encode resistance in human pathogens having originated in bacteria from the natural environment (eg, β-lactamases and fluoroquinolones resistance genes, such as qnr). The rapid evolution and spread of "new" antibiotic resistance genes has been enhanced by modern human activity and its influence on the environmental resistome. This highlights the importance of including the role of the environmental vectors, such as bacterial genetic diversity within soil and water, in resistance risk management. We need to take more steps to decrease the spread of resistance genes in environmental bacteria into human pathogens, to decrease the spread of resistant bacteria to people and animals via foodstuffs, wastes and water, and to minimize the levels of antibiotics and antibiotic-resistant bacteria introduced into the environment. Reducing this risk must include improved management of waste containing antibiotic residues and antibiotic-resistant microorganisms.201323723195
3977130.9999Assessing the Impact of Heat Treatment of Food on Antimicrobial Resistance Genes and Their Potential Uptake by Other Bacteria-A Critical Review. The dissemination of antibiotic resistance genes (ARGs) is a global health concern. This study identifies and critically reviews the published evidence on whether cooking (heating) food to eliminate bacterial contamination induces sufficient damage to the functionality of ARGs. Overall, the review found that there is evidence in the literature that Antimicrobial Resistant (AMR) bacteria are no more heat resistant than non-AMR bacteria. Consequently, recommended heat treatments sufficient to kill non-AMR bacteria in food (70 °C for at least 2 min, or equivalent) should be equally effective in killing AMR bacteria. The literature shows there are several mechanisms through which functional genes from AMR bacteria could theoretically persist in heat-treated food and be transferred to other bacteria. The literature search found sparce published evidence on whether ARGs may actually persist in food after effective heat treatments, and whether functional genes can be transferred to other bacteria. However, three publications have demonstrated that functional ARGs in plasmids may be capable of persisting in foods after effective heat treatments. Given the global impact of AMR, there is clearly a need for further practical research on this topic to provide sufficient evidence to fully assess whether there is a risk to human health from the persistence of functional ARGs in heat-treated and cooked foods.202134943652
7433140.9999Manure as a Potential Hotspot for Antibiotic Resistance Dissemination by Horizontal Gene Transfer Events. The increasing demand for animal-derived foods has led to intensive and large-scale livestock production with the consequent formation of large amounts of manure. Livestock manure is widely used in agricultural practices as soil fertilizer worldwide. However, several antibiotic residues, antibiotic resistance genes (ARGs) and antibiotic-resistant bacteria are frequently detected in manure and manure-amended soils. This review explores the role of manure in the persistence and dissemination of ARGs in the environment, analyzes the procedures used to decrease antimicrobial resistance in manure and the potential impact of manure application in public health. We highlight that manure shows unique features as a hotspot for antimicrobial gene dissemination by horizontal transfer events: richness in nutrients, a high abundance and diversity of bacteria populations and antibiotic residues that may exert a selective pressure on bacteria and trigger gene mobilization; reduction methodologies are able to reduce the concentrations of some, but not all, antimicrobials and microorganisms. Conjugation events are often seen in the manure environment, even after composting. Antibiotic resistance is considered a growing threat to human, animal and environmental health. Therefore, it is crucial to reduce the amount of antimicrobials and the load of antimicrobial resistant bacteria that end up in soil.202032823495
4127150.9999The Perfect Condition for the Rising of Superbugs: Person-to-Person Contact and Antibiotic Use Are the Key Factors Responsible for the Positive Correlation between Antibiotic Resistance Gene Diversity and Virulence Gene Diversity in Human Metagenomes. Human metagenomes with a high diversity of virulence genes tend to have a high diversity of antibiotic-resistance genes and vice-versa. To understand this positive correlation, we simulated the transfer of these genes and bacterial pathogens in a community of interacting people that take antibiotics when infected by pathogens. Simulations show that people with higher diversity of virulence and resistance genes took antibiotics long ago, not recently. On the other extreme, we find people with low diversity of both gene types because they took antibiotics recently-while antibiotics select specific resistance genes, they also decrease gene diversity by eliminating bacteria. In general, the diversity of virulence and resistance genes becomes positively correlated whenever the transmission probability between people is higher than the probability of losing resistance genes. The positive correlation holds even under changes of several variables, such as the relative or total diversity of virulence and resistance genes, the contamination probability between individuals, the loss rate of resistance genes, or the social network type. Because the loss rate of resistance genes may be shallow, we conclude that the transmission between people and antibiotic usage are the leading causes for the positive correlation between virulence and antibiotic-resistance genes.202134065307
9629160.9999Costs of antibiotic resistance genes depend on host strain and environment and can influence community composition. Antibiotic resistance genes (ARGs) benefit host bacteria in environments containing corresponding antibiotics, but it is less clear how they are maintained in environments where antibiotic selection is weak or sporadic. In particular, few studies have measured if the direct effect of ARGs on host fitness is fixed or if it depends on the host strain, perhaps marking some ARG-host combinations as selective refuges that can maintain ARGs in the absence of antibiotic selection. We quantified the fitness effects of six ARGs in 11 diverse Escherichia spp. strains. Three ARGs (bla(TEM-116), cat and dfrA5, encoding resistance to β-lactams, chloramphenicol, and trimethoprim, respectively) imposed an overall cost, but all ARGs had an effect in at least one host strain, reflecting a significant strain interaction effect. A simulation predicts these interactions can cause the success of ARGs to depend on available host strains, and, to a lesser extent, can cause host strain success to depend on the ARGs present in a community. These results indicate the importance of considering ARG effects across different host strains, and especially the potential of refuge strains to allow resistance to persist in the absence of direct selection, in efforts to understand resistance dynamics.202438889784
3996170.9999Antibiotic resistance gene spread due to manure application on agricultural fields. The usage of antibiotics in animal husbandry has promoted the development and abundance of antibiotic resistance in farm environments. Manure has become a reservoir of resistant bacteria and antibiotic compounds, and its application to agricultural soils is assumed to significantly increase antibiotic resistance genes and selection of resistant bacterial populations in soil. The genome location of resistance genes is likely to shift towards mobile genetic elements such as broad-host-range plasmids, integrons, and transposable elements. Horizontal transfer of these elements to bacteria adapted to soil or other habitats supports their environmental transmission independent of the original host. The human exposure to soil-borne resistance has yet to be determined, but is likely to be severely underestimated.201121546307
9630180.9999Novel Insights into Selection for Antibiotic Resistance in Complex Microbial Communities. Recent research has demonstrated that selection for antibiotic resistance occurs at very low antibiotic concentrations in single-species experiments, but the relevance of these findings when species are embedded in complex microbial communities is unclear. We show that the strength of selection for naturally occurring resistance alleles in a complex community remains constant from low subinhibitory to above clinically relevant concentrations. Selection increases with antibiotic concentration before reaching a plateau where selection remains constant over a 2-order-magnitude concentration range. This is likely to be due to cross protection of the susceptible bacteria in the community following rapid extracellular antibiotic degradation by the resistant population, shown experimentally through a combination of chemical quantification and bacterial growth experiments. Metagenome and 16S rRNA analyses of sewage-derived bacterial communities evolved under cefotaxime exposure show preferential enrichment for bla(CTX-M) genes over all other beta-lactamase genes, as well as positive selection and co-selection for antibiotic resistant, opportunistic pathogens. These findings have far-reaching implications for our understanding of the evolution of antibiotic resistance, by challenging the long-standing assumption that selection occurs in a dose-dependent manner.IMPORTANCE Antibiotic resistance is one of the greatest global issues facing society. Still, comparatively little is known about selection for resistance at very low antibiotic concentrations. We show that the strength of selection for clinically important resistance genes within a complex bacterial community can remain constant across a large antibiotic concentration range (wide selective space). Therefore, largely understudied ecological compartments could be just as important as clinical environments for selection of antibiotic resistance.201830042197
4101190.9999What Is the Role of the Environment in the Emergence of Novel Antibiotic Resistance Genes? A Modeling Approach. It is generally accepted that intervention strategies to curb antibiotic resistance cannot solely focus on human and veterinary medicine but must also consider environmental settings. While the environment clearly has a role in transmission of resistant bacteria, its role in the emergence of novel antibiotic resistance genes (ARGs) is less clear. It has been suggested that the environment constitutes an enormous recruitment ground for ARGs to pathogens, but its extent is practically unknown. We have constructed a model framework for resistance emergence and used available quantitative data on relevant processes to identify limiting steps in the appearance of ARGs in human pathogens. We found that in a majority of possible scenarios, the environment would only play a minor role in the emergence of novel ARGs. However, the uncertainty is enormous, highlighting an urgent need for more quantitative data. Specifically, more data is most needed on the fitness costs of ARG carriage, the degree of dispersal of resistant bacteria from the environment to humans, and the rates of mobilization and horizontal transfer of ARGs. This type of data is instrumental to determine which processes should be targeted for interventions to curb development and transmission of ARGs in the environment.202134792330