Antimicrobial resistance and its association with tolerance to heavy metals in agriculture production. - Related Documents




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407701.0000Antimicrobial resistance and its association with tolerance to heavy metals in agriculture production. Antimicrobial resistance is a recognized public health challenge that since its emergence limits the therapeutic options available to veterinarians and clinicians alike, when treatment is warranted. This development is further compounded by the paucity of new antibiotics. The agri-food industry benefits from the availability of antimicrobial compounds for food-animal production and crop protection. Nonetheless, their improper use can result in the selection for bacteria that are phenotypically resistant to these compounds. Another class of agents used in agriculture includes various cationic metals that can be included in animal diets as nutritional supplements or spread on pastures to support crop growth and protection. Heavy metals, in particular, are giving rise to concerns among public health professionals, as they can persist in the environment remaining stable for prolonged periods. Moreover, bacteria can also exhibit resistance to these chemical elements and the genes encoding this phenotype can be physically localized to plasmids that may also contain one or more antimicrobial resistance-encoding gene(s). This paper reviews our current understanding of the role that bacteria play in expressing resistance to heavy metals. It will describe how heavy metals are used in agri-food production, and explore evidence available to link resistance to heavy metals and antimicrobial compounds. In addition, possible solutions to reduce the impact of heavy metal resistance are also discussed, including using organic minerals and reducing the level of trace minerals in animal feed rations.201728213031
406810.9999Co-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
968520.9999Biofilm: A Hotspot for Emerging Bacterial Genotypes. Bacteria have the ability to adapt to changing environments through rapid evolution mediated by modification of existing genetic information, as well as by horizontal gene transfer (HGT). This makes bacteria a highly successful life form when it comes to survival. Unfortunately, this genetic plasticity may result in emergence and dissemination of antimicrobial resistance and virulence genes, and even the creation of multiresistant "superbugs" which may pose serious threats to public health. As bacteria commonly reside in biofilms, there has been an increased interest in studying these phenomena within biofilms in recent years. This review summarizes the present knowledge within this important area of research. Studies on bacterial evolution in biofilms have shown that mature biofilms develop into diverse communities over time. There is growing evidence that the biofilm lifestyle may be more mutagenic than planktonic growth. Furthermore, all three main mechanisms for HGT have been observed in biofilms. This has been shown to occur both within and between bacterial species, and higher transfer rates in biofilms than in planktonic cultures were detected. Of special concern are the observations that mutants with increased antibiotic resistance occur at higher frequency in biofilms than in planktonic cultures even in the absence of antibiotic exposure. Likewise, efficient dissemination of antimicrobial resistance genes, as well as virulence genes, has been observed within the biofilm environment. This new knowledge emphasizes the importance of biofilm awareness and control.201829914658
406730.9999Metal Resistance and Its Association With Antibiotic Resistance. Antibiotic resistance is recognised as a major global threat to public health by the World Health Organization. Currently, several hundred thousand deaths yearly can be attributed to infections with antibiotic-resistant bacteria. The major driver for the development of antibiotic resistance is considered to be the use, misuse and overuse of antibiotics in humans and animals. Nonantibiotic compounds, such as antibacterial biocides and metals, may also contribute to the promotion of antibiotic resistance through co-selection. This may occur when resistance genes to both antibiotics and metals/biocides are co-located together in the same cell (co-resistance), or a single resistance mechanism (e.g. an efflux pump) confers resistance to both antibiotics and biocides/metals (cross-resistance), leading to co-selection of bacterial strains, or mobile genetic elements that they carry. Here, we review antimicrobial metal resistance in the context of the antibiotic resistance problem, discuss co-selection, and highlight critical knowledge gaps in our understanding.201728528649
406040.9999Current status of antibiotic resistance in animal production. It is generally accepted that the more antibiotics we use, the faster bacteria will develop resistance. Further it has been more or less accepted that once an antibiotic is withdrawn from the clinic, the resistance genes will eventually disappear, [table: see text] since they will no more be of any survival value for the bacterial cell. However, recent research has shown that after a long time period of exposure to antibiotics, certain bacterial species may adapt to this environment in such a way that they keep their resistance genes stably also after the removal of antibiotics. Thus, there is reason to believe that once resistance has developed it will not even in the long term be eradicated. What then can we do not to increase further the already high level of antibiotic-resistant bacteria in animals? We should of course encourage a prudent use of these valuable drugs. In Sweden antibiotics are not used for growth promoting purposes and are available only after veterinary prescription on strict indications. Generally, antimicrobial treatment of animals on individual or on herd basis should not be considered unless in connection with relevant diagnostics. The amounts of antibiotics used and the development of resistance in important pathogens should be closely monitored. Furthermore, resistance monitoring in certain non-pathogenic intestinal bacteria, which may serve as a reservoir for resistance genes is probably more important than hitherto anticipated. Once the usage of or resistance to a certain antibiotic seems to increase in an alarming way, steps should be taken to limit the usage of the drug in order to prevent further spread of resistance genes in animals, humans and the environment. Better methods for detecting and quantifying antibiotic resistance have to be developed. Screening methods must be standardized and evaluated in order to obtain comparable and reliable results from different countries. The genetic mechanisms for development of resistance and spread of resistance genes should be studied in detail. Research in these areas will lead to new ideas on how to inhibit the resistance mechanisms. So far, it has been well established that a heavy antimicrobial drug selective pressure in overcrowded populations of production animals creates favourable environments both for the emergence and the spread of antibiotic resistance genes.199910783714
407050.9999Antibiotic Resistance Mechanisms in Bacteria: Relationships Between Resistance Determinants of Antibiotic Producers, Environmental Bacteria, and Clinical Pathogens. Emergence of antibiotic resistant pathogenic bacteria poses a serious public health challenge worldwide. However, antibiotic resistance genes are not confined to the clinic; instead they are widely prevalent in different bacterial populations in the environment. Therefore, to understand development of antibiotic resistance in pathogens, we need to consider important reservoirs of resistance genes, which may include determinants that confer self-resistance in antibiotic producing soil bacteria and genes encoding intrinsic resistance mechanisms present in all or most non-producer environmental bacteria. While the presence of resistance determinants in soil and environmental bacteria does not pose a threat to human health, their mobilization to new hosts and their expression under different contexts, for example their transfer to plasmids and integrons in pathogenic bacteria, can translate into a problem of huge proportions, as discussed in this review. Selective pressure brought about by human activities further results in enrichment of such determinants in bacterial populations. Thus, there is an urgent need to understand distribution of resistance determinants in bacterial populations, elucidate resistance mechanisms, and determine environmental factors that promote their dissemination. This comprehensive review describes the major known self-resistance mechanisms found in producer soil bacteria of the genus Streptomyces and explores the relationships between resistance determinants found in producer soil bacteria, non-producer environmental bacteria, and clinical isolates. Specific examples highlighting potential pathways by which pathogenic clinical isolates might acquire these resistance determinants from soil and environmental bacteria are also discussed. Overall, this article provides a conceptual framework for understanding the complexity of the problem of emergence of antibiotic resistance in the clinic. Availability of such knowledge will allow researchers to build models for dissemination of resistance genes and for developing interventions to prevent recruitment of additional or novel genes into pathogens.201830555448
419760.9999Antibiotic-resistant bacteria: a challenge for the food industry. Antibiotic-resistant bacteria were first described in the 1940s, but whereas new antibiotics were being discovered at a steady rate, the consequences of this phenomenon were slow to be appreciated. At present, the paucity of new antimicrobials coming into the market has led to the problem of antibiotic resistance fast escalating into a global health crisis. Although the selective pressure exerted by the use of antibiotics (particularly overuse or misuse) has been deemed the major factor in the emergence of bacterial resistance to these antimicrobials, concerns about the role of the food industry have been growing in recent years and have been raised at both national and international levels. The selective pressure exerted by the use of antibiotics (primary production) and biocides (e.g., disinfectants, food and feed preservatives, or decontaminants) is the main driving force behind the selection and spread of antimicrobial resistance throughout the food chain. Genetically modified (GM) crops with antibiotic resistance marker genes, microorganisms added intentionally to the food chain (probiotic or technological) with potentially transferable antimicrobial resistance genes, and food processing technologies used at sub-lethal doses (e.g., alternative non-thermal treatments) are also issues for concern. This paper presents the main trends in antibiotic resistance and antibiotic development in recent decades, as well as their economic and health consequences, current knowledge concerning the generation, dissemination, and mechanisms of antibacterial resistance, progress to date on the possible routes for emergence of resistance throughout the food chain and the role of foods as a vehicle for antibiotic-resistant bacteria. The main approaches to prevention and control of the development, selection, and spread of antibacterial resistance in the food industry are also addressed.201323035919
423870.9999Biocide tolerance in bacteria. Biocides have been employed for centuries, so today a wide range of compounds showing different levels of antimicrobial activity have become available. At the present time, understanding the mechanisms of action of biocides has also become an important issue with the emergence of bacterial tolerance to biocides and the suggestion that biocide and antibiotic resistance in bacteria might be linked. While most of the mechanisms providing antibiotic resistance are agent specific, providing resistance to a single antimicrobial or class of antimicrobial, there are currently numerous examples of efflux systems that accommodate and, thus, provide tolerance to a broad range of structurally unrelated antimicrobials, both antibiotics and biocides. If biocide tolerance becomes increasingly common and it is linked to antibiotic resistance, not only resistant (even multi-resistant) bacteria could be passed along the food chain, but also there are resistance determinants that can spread and lead to the emergence of new resistant microorganisms, which can only be detected and monitored when the building blocks of resistance traits are understood on the molecular level. This review summarizes the main advances reached in understanding the mechanism of action of biocides, the mechanisms of bacterial resistance to both biocides and antibiotics, and the incidence of biocide tolerance in bacteria of concern to human health and the food industry.201323340387
968680.9999Selective pressures for public antibiotic resistance. The rapid increase of antibiotic-resistant pathogens is severely limiting our current treatment possibilities. An important subset of the resistance mechanisms conferring antibiotic resistance have public effects, allowing otherwise susceptible bacteria to also survive antibiotic treatment. As susceptible bacteria can survive treatment without bearing the metabolic cost of producing the resistance mechanism, there is potential to increase their relative frequency in the population and, as such, select against resistant bacteria. Multiple studies showed that this altered selection for resistance is dependent on various environmental and treatment parameters. In this review, we provide a comprehensive overview of their most important findings and describe the main factors impacting the selection for resistance. In-depth understanding of the driving forces behind selection can aid in the design and implementation of alternative treatments which limit the risk of resistance development.202539158370
428290.9999Efflux Pump Inhibitors in Controlling Antibiotic Resistance: Outlook under a Heavy Metal Contamination Context. Multi-drug resistance to antibiotics represents a growing challenge in treating infectious diseases. Outside the hospital, bacteria with the multi-drug resistance (MDR) phenotype have an increased prevalence in anthropized environments, thus implying that chemical stresses, such as metals, hydrocarbons, organic compounds, etc., are the source of such resistance. There is a developing hypothesis regarding the role of metal contamination in terrestrial and aquatic environments as a selective agent in the proliferation of antibiotic resistance caused by the co-selection of antibiotic and metal resistance genes carried by transmissible plasmids and/or associated with transposons. Efflux pumps are also known to be involved in either antibiotic or metal resistance. In order to deal with these situations, microorganisms use an effective strategy that includes a range of expressions based on biochemical and genetic mechanisms. The data from numerous studies suggest that heavy metal contamination could affect the dissemination of antibiotic-resistant genes. Environmental pollution caused by anthropogenic activities could lead to mutagenesis based on the synergy between antibiotic efficacy and the acquired resistance mechanism under stressors. Moreover, the acquired resistance includes plasmid-encoded specific efflux pumps. Soil microbiomes have been reported as reservoirs of resistance genes that are available for exchange with pathogenic bacteria. Importantly, metal-contaminated soil is a selective agent that proliferates antibiotic resistance through efflux pumps. Thus, the use of multi-drug efflux pump inhibitors (EPIs) originating from natural plants or synthetic compounds is a promising approach for restoring the efficacy of existing antibiotics, even though they face a lot of challenges.202337049674
4078100.9999Antibiotic resistance in bacteria associated with food animals: a United States perspective of livestock production. The use of antimicrobial compounds in food animal production provides demonstrated benefits, including improved animal health, higher production and, in some cases, reduction in foodborne pathogens. However, use of antibiotics for agricultural purposes, particularly for growth enhancement, has come under much scrutiny, as it has been shown to contribute to the increased prevalence of antibiotic-resistant bacteria of human significance. The transfer of antibiotic resistance genes and selection for resistant bacteria can occur through a variety of mechanisms, which may not always be linked to specific antibiotic use. Prevalence data may provide some perspective on occurrence and changes in resistance over time; however, the reasons are diverse and complex. Much consideration has been given this issue on both domestic and international fronts, and various countries have enacted or are considering tighter restrictions or bans on some types of antibiotic use in food animal production. In some cases, banning the use of growth-promoting antibiotics appears to have resulted in decreases in prevalence of some drug resistant bacteria; however, subsequent increases in animal morbidity and mortality, particularly in young animals, have sometimes resulted in higher use of therapeutic antibiotics, which often come from drug families of greater relevance to human medicine. While it is clear that use of antibiotics can over time result in significant pools of resistance genes among bacteria, including human pathogens, the risk posed to humans by resistant organisms from farms and livestock has not been clearly defined. As livestock producers, animal health experts, the medical community, and government agencies consider effective strategies for control, it is critical that science-based information provide the basis for such considerations, and that the risks, benefits, and feasibility of such strategies are fully considered, so that human and animal health can be maintained while at the same time limiting the risks from antibiotic-resistant bacteria.200717600481
9681110.9999Uses of antimicrobials in plant agriculture. Bacterial diseases of plants are less prevalent than diseases caused by fungi and viruses. Antimicrobials for prophylactic treatment of bacterial diseases of plants are limited in availability, use, and efficacy, and therapeutic use is largely ineffective. Most applications are by spray treatments in orchards. Monitoring and surveillance for drug resistance are not routinely done. In the United States, data on use of antimicrobials for treatment of bacterial diseases of plants are limited to streptomycin and oxytetracycline. Resistance to streptomycin has become widespread among bacterial phytopathogens; no resistance among these bacteria has yet been reported for oxytetracycline. No human health effects have been documented since inception of use of antimicrobials in plants in the 1950s. Transfer of antimicrobial resistance from marker genes in transgenic plants to bacteria has not been documented under natural conditions in field-grown plants. However, antimicrobial-resistance genes are being eliminated from use as marker genes because of concerns about possible transfer from plant genomes back to bacteria, with further horizontal transfer to the bacteria in the environment, or from plant genomes to animals by plant consumption. No new antimicrobials are expected to be used in plant agriculture because of high costs of development, regulatory constraints, and environmental and human health concerns. Alternatives to antimicrobials, such as biocontrol agents, transgenic plants, and novel chemicals, are being developed and marketed, although their efficacy remains to be determined.200211988880
9684120.9999Pesticide degrading natural multidrug resistance bacterial flora. Multidrug-resistant (MDR) bacteria are a growing threat to humans across the world. Antibiotic resistance is a global problem that has developed through continuous antibiotic use, combinatorial antibiotic use, pesticide-antibiotic cross-resistance, and horizontal gene transfer, as well as various other modes. Pesticide-antibiotic cross-resistance and the subsequent expansion of drug-resistant bacteria are critically documented in this review, the primary focus of which is to assess the impact of indiscriminate pesticide use on the development of microbial communities with parallel pesticide and multidrug resistance. The consumption of pesticide-contaminated food products and the use of broad-spectrum antibiotics by humans and in livestock animals have favored the development of both antibiotic and pesticide-resistant bacterial flora via natural selection. Pesticide resistance mainly develops through defensive bacterial adaptations such as biofilm formation, induced mutations, and horizontal/vertical gene transfer through plasmids or transposons, as well as through the increased expression of certain hydrolytic enzymes. Pesticide resistance genes are always transferred as gene clusters, and they may also carry genes essential for antibiotic resistance. Moreover, for some induced mutations, the mutated active site of the affected enzyme may allow degradation of both pesticides and antibiotics, resulting in cross-resistance. A few studies have shown that the sub-lethal exposure of wild-type strains to herbicides induces antibiotic resistance. This review concludes that xenobiotic exposure leads to cross-resistance in wild microbial flora, which requires further study to develop therapeutic approaches to overcome the threats of MDR bacteria and superbugs.201829223450
4231130.9999Recent investigations and updated criteria for the assessment of antibiotic resistance in food lactic acid bacteria. The worldwide use, and misuse, of antibiotics for about sixty years in the so-called antibiotic era, has been estimated in some one to ten million tons, a relevant part of which destined for non-therapeutic purposes such as growth promoting treatments for livestock or crop protection. As highly adaptable organisms, bacteria have reacted to this dramatic change in their environment by developing several well-known mechanisms of antibiotic resistance and are becoming increasingly resistant to conventional antibiotics. In recent years, commensal bacteria have become a cause of concern since they may act as reservoirs for the antibiotic resistance genes found in human pathogens. In particular, the food chain has been considered the main route for the introduction of animal and environment associated antibiotic resistant bacteria into the human gastrointestinal tract (GIT) where these genes may be transferred to pathogenic and opportunistic bacteria. As fundamental microbial communities in a large variety of fermented foods and feed, the anaerobe facultative, aerotolerant lactic acid bacteria (LAB) are likely to play a pivotal role in the resistance gene exchange occurring in the environment, food, feed and animal and human GIT. Therefore their antibiotic resistance features and their genetic basis have recently received increasing attention. The present article summarises the results of the latest studies on the most typical genera belonging to the low G + C branch of LAB. The evolution of the criteria established by European regulatory bodies to ensure a safe use of microorganisms in food and feed, including the assessment of their antibiotic resistance is also reviewed.201121515393
9456140.9999Antibiotic treatments and microbes in the gut. Antibiotic therapies are important in combating disease-causing microorganisms and maintaining host health. It is widely accepted that exposure of the gut microbiota to antibiotics can lead to decreased susceptibility and the development of multi-drug-resistant disease-causing organisms, which can be a major clinical problem. It is also important to consider that antibiotics not only target pathogenic bacteria in the gut, but also can have damaging effects on the ecology of commensal species. This can reduce intrinsic colonization resistance and contribute to problems with antibiotic resistance, including lateral transfer of resistance genes. Our knowledge of the impact of antibiotic treatment on the ecology of the normal microbiota has been increased by recent advances in molecular methods and use of in vitro model systems to investigate the impact of antibiotics on the biodiversity of gut populations and the spread of antibiotic resistance. These highlight the need for more detailed structural and functional information on the long-term antibiotic-associated alterations in the gut microbiome, and spread of antibiotic resistance genes. This will be crucial for the development of strategies, such as targeted therapeutics, probiotics, prebiotics and synbiotics, to prevent perturbations in the gut microbiota, the restoration of beneficial species and improvements in host health.201424471523
4016150.9999Antimicrobial-induced horizontal transfer of antimicrobial resistance genes in bacteria: a mini-review. The emergence and spread of antimicrobial resistance (AMR) among pathogenic bacteria constitute an accelerating crisis for public health. The selective pressures caused by increased use and misuse of antimicrobials in medicine and livestock production have accelerated the overall selection of resistant bacteria. In addition, horizontal gene transfer (HGT) plays an important role in the spread of resistance genes, for example mobilizing reservoirs of AMR from commensal bacteria into pathogenic ones. Antimicrobials, besides antibacterial function, also result in undesirable effects in the microbial populations, including the stimulation of HGT. The main aim of this narrative review was to present an overview of the current knowledge of the impact of antimicrobials on HGT in bacteria, including the effects of transformation, transduction and conjugation, as well as other less well-studied mechanisms of HGT. It is widely accepted that conjugation plays a major role in the spread of AMR in bacteria, and the focus of this review is therefore mainly on the evidence provided that antimicrobial treatment affects this process. Other mechanisms of HGT have so far been deemed less important in this respect; however, recent discoveries suggest their role may be larger than previously thought, and the review provides an update on the rather limited knowledge currently available regarding the impact of antimicrobial treatment on these processes as well. A conclusion from the review is that there is an urgent need to investigate the mechanisms of antimicrobial-induced HGT, since this will be critical for developing new strategies to combat the spread of AMR.202234894259
4076160.9999Overuse of food-grade disinfectants threatens a global spread of antimicrobial-resistant bacteria. Food-grade disinfectants are extensively used for microbial decontamination of food processing equipment. In recent years, food-grade disinfectants have been increasingly used. However, the overuse of disinfectants causes another major issue, which is the emergence and spread of antimicrobial-resistant bacteria on a global scale. As the ongoing pandemic takes global attention, bacterial infections with antibiotic resistance are another ongoing pandemic that often goes unnoticed and will be the next real threat to humankind. Here, the effects of food-grade disinfectant overuse on the global emergence and spread of antimicrobial-resistant bacteria were reviewed. It was found that longtime exposure to the most common food-grade disinfectants promoted resistance to clinically important antibiotics in pathogenic bacteria, namely cross-resistance. Currently, the use of disinfectants is largely unregulated. The mechanisms of cross-resistance are regulated by intrinsic molecular mechanisms including efflux pumps, DNA repair system, modification of the molecular target, and metabolic adaptation. Cross-resistance can also be acquired by mobile genetic elements. Long-term exposure to disinfectants has an impact on the dissemination of antimicrobial resistance in soil, plants, animals, water, and human gut environments.202436756870
9455170.9999Prospects and Challenges of Bacteriophage Substitution for Antibiotics in Livestock and Poultry Production. The overuse and misuse of antibiotics in the livestock and poultry industry has led to the development of multi-drug resistance in animal pathogens, and antibiotic resistance genes (ARGs) in bacteria transfer from animals to humans through the consumption of animal products, posing a serious threat to human health. Therefore, the use of antibiotics in livestock production has been strictly controlled. As a result, bacteriophages have attracted increasing research interest as antibiotic alternatives, since they are natural invaders of bacteria. Numerous studies have shown that dietary bacteriophage supplementation could regulate intestinal microbial composition, enhance mucosal immunity and the physical barrier function of the intestinal tract, and play an important role in maintaining intestinal microecological stability and normal body development of animals. The effect of bacteriophages used in animals is influenced by factors such as species, dose, and duration. However, as a category of mobile genetic elements, the high frequency of gene exchange of bacteriophages also poses risks of transmitting ARGs among bacteria. Hence, we summarized the mechanism and efficacy of bacteriophage therapy, and highlighted the feasibility and challenges of bacteriophage utilization in farm animal production, aiming to provide a reference for the safe and effective application of bacteriophages as an antibiotic alternative in livestock and poultry.202438248459
4075180.9999Antimicrobial resistance in foodborne pathogens--a cause for concern? The widespread use of antibiotics in food animal production systems has resulted in the emergence of antibiotic resistant zoonotic bacteria that can be transmitted to humans through the food chain. Infection with antibiotic resistant bacteria negatively impacts on public health, due to an increased incidence of treatment failure and severity of disease. Development of resistant bacteria in food animals can result from chromosomal mutations but is more commonly associated with the horizontal transfer of resistance determinants borne on mobile genetic elements. Food may represent a dynamic environment for the continuing transfer of antibiotic resistance determinants between bacteria. Current food preservation systems that use a combination of environmental stresses to reduce growth of bacteria, may serve to escalate development and dissemination of antibiotic resistance among food related pathogens. The increasing reliance on biocides for pathogen control in food production and processing, heightens the risk of selection of biocide-resistant strains. Of particular concern is the potential for sublethal exposure to biocides to select for bacteria with enhanced multi-drug efflux pump activity capable of providing both resistance to biocides and cross-resistance to multiple antibiotics. Although present evidence suggests that biocide resistance is associated with a physiological cost, the possibility of the development of adaptive mutations conferring increased fitness cannot be ruled-out. Strategies aimed at inhibiting efflux pumps and eliminating plasmids could help to restore therapeutic efficacy to antibiotics and reduce the spread of antibiotic resistant foodborne pathogens through the food chain.200818781926
4225190.9999Safety aspects and implications of regulation of probiotic bacteria in food and food supplements. The application of living bacteria as probiotics in food or food supplements requires a careful safety assessment. This review summarizes key issues concerning the safety aspects of bacteria added to particular products marketed for improvement of general health or treatment of (post)infectious symptoms. The bacteria used in such products should be completely safe; however, it can be challenging to provide evidence for absence of all virulence properties. In some cases, virulence factors have been detected in probiotic bacterial strains, and the implications of these traits for safety assessments are discussed. Horizontal gene transfer can result in acquisition of virulence genes or antimicrobial resistance in probiotic bacteria. Antimicrobial resistance in these bacteria can possibly aid the spread of undesired resistance in intestinal bacterial populations. The relative risk of such gene transfers is considered. The generation of complete bacterial genome sequences can both resolve and create safety issues. Current practices of safety assessment procedures in the United States and the European Union are briefly reviewed and a future outlook is provided.200818724773