Heavy Metals as Catalysts in the Evolution of Antimicrobial Resistance and the Mechanisms Underpinning Co-selection. - Related Documents




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963701.0000Heavy Metals as Catalysts in the Evolution of Antimicrobial Resistance and the Mechanisms Underpinning Co-selection. The menace caused by antibiotic resistance in bacteria is acknowledged on a global scale. Concerns over the same are increasing because of the selection pressure exerted by a huge number of different antimicrobial agents, including heavy metals. Heavy metals are non-metabolizable and recalcitrant to degradation, therefore the bacteria can expel the pollutants out of the system and make it less harmful via different mechanisms. The selection of antibiotic-resistant bacteria may be influenced by heavy metals present in environmental reservoirs. Through co-resistance and cross-resistance processes, the presence of heavy metals in the environment can act as co-selecting agents, hence increasing resistance to both heavy metals and antibiotics. The horizontal gene transfer or mutation assists in the selection of mutant bacteria resistant to the polluted environment. Hence, bioremediation and biodegradation are sustainable methods for the natural clean-up of pollutants. This review sheds light on the occurrence of metal and antibiotic resistance in the environment via the co-resistance and cross-resistance mechanisms underpinning co-selection emphasizing the dearth of studies that specifically examine the method of co-selection in clinical settings. Furthermore, it is advised that future research incorporate both culture- and molecular-based methodologies to further our comprehension of the mechanisms underlying bacterial co- and cross-resistance to antibiotics and heavy metals.202438642082
428310.9999Development, spread and persistence of antibiotic resistance genes (ARGs) in the soil microbiomes through co-selection. Bacterial pathogens resistant to multiple antibiotics are emergent threat to the public health which may evolve in the environment due to the co-selection of antibiotic resistance, driven by poly aromatic hydrocarbons (PAHs) and/or heavy metal contaminations. The co-selection of antibiotic resistance (AMR) evolves through the co-resistance or cross-resistance, or co-regulatory mechanisms, present in bacteria. The persistent toxic contaminants impose widespread pressure in both clinical and environmental setting, and may potentially cause the maintenance and spread of antibiotic resistance genes (ARGs). In the past few years, due to exponential increase of AMR, numerous drugs are now no longer effective to treat infectious diseases, especially in cases of bacterial infections. In this mini-review, we have described the role of co-resistance and cross-resistance as main sources for co-selection of ARGs; while other co-regulatory mechanisms are also involved with cross-resistance that regulates multiple ARGs. However, co-factors also support selections, which results in development and evolution of ARGs in absence of antibiotic pressure. Efflux pumps present on the same mobile genetic elements, possibly due to the function of Class 1 integrons (Int1), may increase the presence of ARGs into the environment, which further is promptly changed as per environmental conditions. This review also signifies that mutation plays important role in the expansion of ARGs due to presence of diverse types of anthropogenic pollutants, which results in overexpression of efflux pump with higher bacterial fitness cost; and these situations result in acquisition of resistant genes. The future aspects of co-selection with involvement of systems biology, synthetic biology and gene network approaches have also been discussed.202032681784
428420.9999Overview on the role of heavy metals tolerance on developing antibiotic resistance in both Gram-negative and Gram-positive bacteria. Environmental health is a critical concern, continuously contaminated by physical and biological components (viz., anthropogenic activity), which adversely affect on biodiversity, ecosystems and human health. Nonetheless, environmental pollution has great impact on microbial communities, especially bacteria, which try to evolve in changing environment. For instance, during the course of adaptation, bacteria easily become resistance to antibiotics and heavy metals. Antibiotic resistance genes are now one of the most vital pollutants, provided as a source of frequent horizontal gene transfer. In this review, the environmental cause of multidrug resistance (MDR) that was supposed to be driven by either heavy metals or combination of environmental factors was essentially reviewed, especially focussed on the correlation between accumulation of heavy metals and development of MDR by bacteria. This kind of correlation was seemed to be non-significant, i.e. paradoxical. Gram-positive bacteria accumulating much of toxic heavy metal (i.e. highly stress tolerance) were unlikely to become MDR, whereas Gram-negative bacteria that often avoid accumulation of toxic heavy metal by efflux pump systems were come out to be more prone to MDR. So far, other than antibiotic contaminant, no such available data strongly support the direct influence of heavy metals in bacterial evolution of MDR; combinations of factors may drive the evolution of antibiotic resistance. Therefore, Gram-positive bacteria are most likely to be an efficient member in treatment of industrial waste water, especially in the removal of heavy metals, perhaps inducing the less chance of antibiotic resistance pollution in the environment.202133811263
646530.9999Knowledge gaps in the assessment of antimicrobial resistance in surface waters. The spread of antibiotic resistance in the water environment has been widely described. However, still many knowledge gaps exist regarding the selection pressure from antibiotics, heavy metals and other substances present in surface waters as a result of anthropogenic activities, as well as the extent and impact of this phenomenon on aquatic organisms and humans. In particular, the relationship between environmental concentrations of antibiotics and the acquisition of ARGs by antibiotic-sensitive bacteria as well as the impact of heavy metals and other selective agents on antimicrobial resistance (AMR) need to be defined. Currently, established safety values are based on the effects of antibiotic toxicity neglecting the question of AMR spread. In turn, risk assessment of antibiotics in waterbodies remains a complex question implicating multiple variables and unknowns reinforced by the lack of harmonized protocols and official guidelines. In the present review, we discussed current state-of-the-art and the knowledge gaps related to pressure exerted by antibiotics and heavy metals on aquatic environments and their relationship to the spread of AMR. Along with this latter, we reflected on (i) the risk assessment in surface waters, (ii) selective pressures contributing to its transfer and propagation and (iii) the advantages of metagenomics in investigating AMR. Furthermore, the role of microplastics in co-selection for metal and antibiotic resistance, together with the need for more studies in freshwater are highlighted.202134625810
406840.9999Co-selection for antibiotic resistance by environmental contaminants. The environment is increasingly recognised as a hotspot for the selection and dissemination of antibiotic resistant bacteria and antibiotic resistance genes. These can be selected for by antibiotics and non-antibiotic agents (such as metals and biocides), with the evidence to support this well established by observational and experimental studies. However, there is emerging evidence to suggest that plant protection products (such as herbicides), and non-antibiotic drugs (such as chemotherapeutic agents), can also co-select for antibiotic resistance. This review aims to provide an overview of four classes of non-antibiotic agents (metals, biocides, plant protection products, and non-antibiotic drugs) and how they may co-select for antibiotic resistance, with a particular focus on the environment. It also aims to identify key knowledge gaps that should be addressed in future work, to better understand these potential co-selective agents.202439843965
963950.9999Co-selection mechanism for bacterial resistance to major chemical pollutants in the environment. Bacterial resistance is an emerging global public health problem, posing a significant threat to animal and human health. Chemical pollutants present in the environment exert selective pressure on bacteria, which acquire resistance through co-resistance, cross-resistance, co-regulation, and biofilm resistance. Resistance genes are horizontally transmitted in the environment through four mechanisms including conjugation transfer, bacterial transformation, bacteriophage transduction, and membrane vesicle transport, and even enter human bodies through the food chain, endangering human health. Although the co-selection effects of bacterial resistance to chemical pollutants has attracted widespread attention, the co-screening mechanism and co-transmission mechanisms remain unclear. Therefore, this article summarises the current research status of the co-selection effects and mechanism of environmental pollutants resistance, emphasising the necessity of studying the co-selection mechanism of bacteria against major chemical pollutants, and lays a solid theoretical foundation for conducting risk assessment of bacterial resistance.202438101638
646060.9999Biocides as drivers of antibiotic resistance: A critical review of environmental implications and public health risks. The widespread and indiscriminate use of biocides poses significant threats to global health, socioeconomic development, and environmental sustainability by accelerating antibiotic resistance. Bacterial resistance development is highly complex and influenced significantly by environmental factors. Increased biocide usage in households, agriculture, livestock farming, industrial settings, and hospitals produces persistent chemical residues that pollute soil and aquatic environments. Such contaminants contribute to the selection and proliferation of resistant bacteria and antimicrobial resistance genes (ARGs), facilitating their dissemination among humans, animals, and ecosystems. In this review, we conduct a critical assessment of four significant issues pertaining to this topic. Specifically, (i) the role of biocides in exerting selective pressure within the environmental resistome, thereby promoting the proliferation of resistant microbial populations and contributing to the global spread of antimicrobial resistance genes (ARGs); (ii) the role of biocides in triggering transient phenotypic adaptations in bacteria, including efflux pump overexpression, membrane alterations, and reduced porin expression, which often result in cross-resistance to multiple antibiotics; (iii) the capacity of biocides to disrupt bacteria and make the genetic content accessible, releasing DNA into the environment that remains intact under certain conditions, facilitating horizontal gene transfer and the spread of resistance determinants; (iv) the capacity of biocides to disrupt bacterial cells, releasing intact DNA into the environment and enhancing horizontal gene transfer of resistance determinants; and (iv) the selective interactions between biocides and bacterial biofilms in the environment, strengthening biofilm cohesion, inducing resistance mechanisms, and creating reservoirs for resistant microorganisms and ARG dissemination. Collectively, this review highlights the critical environmental and public health implications of biocide use, emphasizing an urgent need for strategic interventions to mitigate their role in antibiotic resistance proliferation.202540230384
398870.9999The Phenomenon of Antibiotic Resistance in the Polar Regions: An Overview of the Global Problem. The increasing prevalence of antibiotic resistance is a global problem in human and animal health. This leads to a reduction in the therapeutic effectiveness of the measures used so far and to the limitation of treatment options, which may pose a threat to human health and life. The problem of phenomenon of antibiotic resistance affects more and more the polar regions. This is due to the increase in tourist traffic and the number of people staying at research stations, unmodernised sewage systems in inhabited areas, as well as the migration of animals or the movement of microplastics, which may contain resistant bacteria. Research shows that the presence of antibiotic resistance genes is more dominant in zones of human and wildlife influence than in remote areas. In a polluted environment, there is evidence of a direct correlation between human activity and the spread and survival of antibiotic-resistant bacteria. Attention should be paid to the presence of resistance to synthetic and semi-synthetic antibiotics in the polar regions, which is likely to be correlated with human presence and activity, and possible steps to be taken. We need to understand many more aspects of this, such as bacterial epigenetics and environmental stress, in order to develop effective strategies for minimizing the spread of antibiotic resistance genes. Studying the diversity and abundance of antibiotic resistance genes in regions with less anthropogenic activity could provide insight into the diversity of primary genes and explain the historical evolution of antibiotic resistance.202337034396
646980.9999From environment to clinic: the role of pesticides in antimicrobial resistance. Antimicrobial resistance (AMR) in pathogens has been associated mainly with excessive use of antibiotics. Most studies of resistance have focused on clinical pathogens; however, microorganisms are exposed to numerous anthropogenic substances. Few studies have sought to determine the effects of chemical substances on microorganisms. Exposure to these substances may contribute to increased rates of AMR. Understanding microorganism communities in natural environments and AMR mechanisms under the effects of anthropogenic substances, such as pesticides, is important to addressing the current crisis of antimicrobial resistance. This report draws attention to molecules, rather than antibiotics, that are commonly used in agrochemicals and may be involved in developing AMR in non-clinical environments, such as soil. This report examines pesticides as mediators for the appearance of AMR, and as a route for antibiotic resistance genes and antimicrobial resistant bacteria to the anthropic environment. Available evidence suggests that the natural environment may be a key dissemination route for antibiotic-resistant genes. Understanding the interrelationship of soil, water, and pesticides is fundamental to raising awareness of the need for environmental monitoring programs and overcoming the current crisis of AMR.202032973897
646690.9999The antibiotic resistome: gene flow in environments, animals and human beings. The antibiotic resistance is natural in bacteria and predates the human use of antibiotics. Numerous antibiotic resistance genes (ARGs) have been discovered to confer resistance to a wide range of antibiotics. The ARGs in natural environments are highly integrated and tightly regulated in specific bacterial metabolic networks. However, the antibiotic selection pressure conferred by the use of antibiotics in both human medicine and agriculture practice leads to a significant increase of antibiotic resistance and a steady accumulation of ARGs in bacteria. In this review, we summarized, with an emphasis on an ecological point of view, the important research progress regarding the collective ARGs (antibiotic resistome) in bacterial communities of natural environments, human and animals, i.e., in the one health settings.We propose that the resistance gene flow in nature is "from the natural environments" and "to the natural environments"; human and animals, as intermediate recipients and disseminators, contribute greatly to such a resistance gene "circulation."201728500429
6476100.9999Sustainable strategies: Nature-based solutions to tackle antibiotic resistance gene proliferation and improve agricultural productivity and soil quality. The issue of antibiotic resistance is now recognized by the World Health Organisation (WHO) as one of the major problems in human health. Although its effects are evident in the healthcare settings, the root cause should be traced back to the One Health link, extending from animals to the environment. In fact, the use of organic fertilizers in agroecosystems represents one, if not the primary, cause of the introduction of antibiotics and antibiotic-resistant bacteria into the soil. Since the concentrations of antibiotics introduced into the soil are residual, the agroecosystem has become a perfect environment for the selection and proliferation of antibiotic resistance genes (ARGs). The continuous influx of these emerging contaminants (i.e., antibiotics) into the agroecosystem results in the selection and accumulation of ARGs in soil bacteria, occasionally giving rise to multi-resistant bacteria. These bacteria may harbour ARGs related to various antibiotics on their plasmids. In this context, these bacteria can potentially enter the human sphere when individuals consume food from contaminated agroecosystems, leading to the acquisition of multi-resistant bacteria. Once introduced into the nosocomial environment, these bacteria pose a significant threat to human health. In this review, we analyse how the use of digestate as an organic fertilizer can mitigate the spread of ARGs in agroecosystems. Furthermore, we highlight how, according to European guidelines, digestate can be considered a Nature-Based Solution (NBS). This NBS not only has the ability to mitigate the spread of ARGs in agroecosystems but also offers the opportunity to further improve Microbial-Based Solutions (MBS), with the aim of enhancing soil quality and productivity.202438307185
3993110.9999Environmental 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
4102120.9999Forces shaping the antibiotic resistome. Antibiotic resistance has become a problem of global scale. Resistance arises through mutation or through the acquisition of resistance gene(s) from other bacteria in a process called horizontal gene transfer (HGT). While HGT is recognized as an important factor in the dissemination of resistance genes in clinical pathogens, its role in the environment has been called into question by a recent study published in Nature. The authors found little evidence of HGT in soil using a culture-independent functional metagenomics approach, which is in contrast to previous work from the same lab showing HGT between the environment and human microbiome. While surprising at face value, these results may be explained by the lack of selective pressure in the environment studied. Importantly, this work suggests the need for careful monitoring of environmental antibiotic pollution and stringent antibiotic stewardship in the fight against resistance.201425213620
9638130.9999Response of microbial antibiotic resistance to pesticides: An emerging health threat. The spread of microbial antibiotic resistance has seriously threatened public health globally. Non-antibiotic stressors have significantly contributed to the evolution of bacterial antibiotic resistance. Although numerous studies have been conducted on the potential risk of pesticide pollution for bacterial antibiotic resistance, a systematic review of these concerns is still lacking. In the present study, we elaborate the mechanism underlying the effects of pesticides on bacterial antibiotic resistance acquisition as well as the propagation of antimicrobial resistance. Pesticide stress enhanced the acquisition of antibiotic resistance in bacteria via various mechanisms, including the activation of efflux pumps, inhibition of outer membrane pores for resistance to antibiotics, and gene mutation induction. Horizontal gene transfer is a major mechanism whereby pesticides influence the transmission of antibiotic resistance genes (ARGs) in bacteria. Pesticides promoted the conjugation transfer of ARGs by increasing cell membrane permeability and increased the proportion of bacterial mobile gene elements, which facilitate the spread of ARGs. This review can improve our understanding regarding the pesticide-induced generation and spread of ARGs and antibiotic resistant bacteria. Moreover, it can be applied to reduce the ecological risks of ARGs in the future.202235977623
6467140.9999The role of biofilms as environmental reservoirs of antibiotic resistance. Antibiotic resistance has become a significant and growing threat to public and environmental health. To face this problem both at local and global scales, a better understanding of the sources and mechanisms that contribute to the emergence and spread of antibiotic resistance is required. Recent studies demonstrate that aquatic ecosystems are reservoirs of resistant bacteria and antibiotic resistance genes as well as potential conduits for their transmission to human pathogens. Despite the wealth of information about antibiotic pollution and its effect on the aquatic microbial resistome, the contribution of environmental biofilms to the acquisition and spread of antibiotic resistance has not been fully explored in aquatic systems. Biofilms are structured multicellular communities embedded in a self-produced extracellular matrix that acts as a barrier to antibiotic diffusion. High population densities and proximity of cells in biofilms also increases the chances for genetic exchange among bacterial species converting biofilms in hot spots of antibiotic resistance. This review focuses on the potential effect of antibiotic pollution on biofilm microbial communities, with special emphasis on ecological and evolutionary processes underlying acquired resistance to these compounds.201526583011
4017150.9999Non-antibiotic compounds associated with humans and the environment can promote horizontal transfer of antimicrobial resistance genes. Horizontal gene transfer plays a key role in the global dissemination of antimicrobial resistance (AMR). AMR genes are often carried on self-transmissible plasmids, which are shared amongst bacteria primarily by conjugation. Antibiotic use has been a well-established driver of the emergence and spread of AMR. However, the impact of commonly used non-antibiotic compounds and environmental pollutants on AMR spread has been largely overlooked. Recent studies found common prescription and over-the-counter drugs, artificial sweeteners, food preservatives, and environmental pollutants, can increase the conjugative transfer of AMR plasmids. The potential mechanisms by which these compounds promote plasmid transmission include increased membrane permeability, upregulation of plasmid transfer genes, formation of reactive oxygen species, and SOS response gene induction. Many questions remain around the impact of most non-antibiotic compounds on AMR plasmid conjugation in clinical isolates and the long-term impact on AMR dissemination. By elucidating the role of routinely used pharmaceuticals, food additives, and pollutants in the dissemination of AMR, action can be taken to mitigate their impact by closely monitoring use and disposal. This review will discuss recent progress on understanding the influence of non-antibiotic compounds on plasmid transmission, the mechanisms by which they promote transfer, and the level of risk they pose.202437462915
4285160.9999Living with sulfonamides: a diverse range of mechanisms observed in bacteria. Sulfonamides are the oldest class of synthetic antibiotics still in use in clinical and veterinary settings. The intensive utilization of sulfonamides has been leading to the widespread contamination of the environment with these xenobiotic compounds. Consequently, in addition to pathogens and commensals, also bacteria inhabiting a wide diversity of environmental compartments have been in contact with sulfonamides for almost 90 years. This review aims at giving an overview of the effect of sulfonamides on bacterial cells, including the strategies used by bacteria to cope with these bacteriostatic agents. These include mechanisms of antibiotic resistance, co-metabolic transformation, and partial or total mineralization of sulfonamides. Possible implications of these mechanisms on the ecosystems and dissemination of antibiotic resistance are also discussed. KEY POINTS: • Sulfonamides are widespread xenobiotic pollutants; • Target alteration is the main sulfonamide resistance mechanism observed in bacteria; • Sulfonamides can be modified, degraded, or used as nutrients by some bacteria.202033175245
3994170.9999Environmental 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
6463180.9999Antibiotic resistance in urban aquatic environments: can it be controlled? Over the last decade, numerous evidences have contributed to establish a link between the natural and human-impacted environments and the growing public health threat that is the antimicrobial resistance. In the environment, in particular in areas subjected to strong anthropogenic pressures, water plays a major role on the transformation and transport of contaminants including antibiotic residues, antibiotic-resistant bacteria, and antibiotic resistance genes. Therefore, the urban water cycle, comprising water abstraction, disinfection, and distribution for human consumption, and the collection, treatment, and delivery of wastewater to the environment, is a particularly interesting loop to track the fate of antibiotic resistance in the environment and to assess the risks of its transmission back to humans. In this article, the relevance of different transepts of the urban water cycle on the potential enrichment and spread of antibiotic resistance is reviewed. According to this analysis, some gaps of knowledge, research needs, and control measures are suggested. The critical rationale behind the measures suggested and the desirable involvement of some key action players is also discussed.201626649735
6462190.9999Human 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