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938800.9972Suboptimal environmental conditions prolong phage epidemics in bacterial populations. Infections by filamentous phages, which are usually nonlethal to the bacterial cells, influence bacterial fitness in various ways. While phage-encoded accessory genes, for example virulence genes, can be highly beneficial, the production of viral particles is energetically costly and often reduces bacterial growth. Consequently, if costs outweigh benefits, bacteria evolve resistance, which can shorten phage epidemics. Abiotic conditions are known to influence the net-fitness effect for infected bacteria. Their impact on the dynamics and trajectories of host resistance evolution, however, remains yet unknown. To address this, we experimentally evolved the bacterium Vibrio alginolyticus in the presence of a filamentous phage at three different salinity levels, that is (1) ambient, (2) 50% reduction and (3) fluctuations between reduced and ambient. In all three salinities, bacteria rapidly acquired resistance through super infection exclusion (SIE), whereby phage-infected cells acquired immunity at the cost of reduced growth. Over time, SIE was gradually replaced by evolutionary fitter surface receptor mutants (SRM). This replacement was significantly faster at ambient and fluctuating conditions compared with the low saline environment. Our experimentally parameterized mathematical model explains that suboptimal environmental conditions, in which bacterial growth is slower, slow down phage resistance evolution ultimately prolonging phage epidemics. Our results may explain the high prevalence of filamentous phages in natural environments where bacteria are frequently exposed to suboptimal conditions and constantly shifting selections regimes. Thus, our future ocean may favour the emergence of phage-born pathogenic bacteria and impose a greater risk for disease outbreaks, impacting not only marine animals but also humans.202437337348
960010.9972Novel "Superspreader" Bacteriophages Promote Horizontal Gene Transfer by Transformation. Bacteriophages infect an estimated 10(23) to 10(25) bacterial cells each second, many of which carry physiologically relevant plasmids (e.g., those encoding antibiotic resistance). However, even though phage-plasmid interactions occur on a massive scale and have potentially significant evolutionary, ecological, and biomedical implications, plasmid fate upon phage infection and lysis has not been investigated to date. Here we show that a subset of the natural lytic phage population, which we dub "superspreaders," releases substantial amounts of intact, transformable plasmid DNA upon lysis, thereby promoting horizontal gene transfer by transformation. Two novel Escherichia coli phage superspreaders, SUSP1 and SUSP2, liberated four evolutionarily distinct plasmids with equal efficiency, including two close relatives of prominent antibiotic resistance vectors in natural environments. SUSP2 also mediated the extensive lateral transfer of antibiotic resistance in unbiased communities of soil bacteria from Maryland and Wyoming. Furthermore, the addition of SUSP2 to cocultures of kanamycin-resistant E. coli and kanamycin-sensitive Bacillus sp. bacteria resulted in roughly 1,000-fold more kanamycin-resistant Bacillus sp. bacteria than arose in phage-free controls. Unlike many other lytic phages, neither SUSP1 nor SUSP2 encodes homologs to known hydrolytic endonucleases, suggesting a simple potential mechanism underlying the superspreading phenotype. Consistent with this model, the deletion of endonuclease IV and the nucleoid-disrupting protein ndd from coliphage T4, a phage known to extensively degrade chromosomal DNA, significantly increased its ability to promote plasmid transformation. Taken together, our results suggest that phage superspreaders may play key roles in microbial evolution and ecology but should be avoided in phage therapy and other medical applications. IMPORTANCE: Bacteriophages (phages), viruses that infect bacteria, are the planet's most numerous biological entities and kill vast numbers of bacteria in natural environments. Many of these bacteria carry plasmids, extrachromosomal DNA elements that frequently encode antibiotic resistance. However, it is largely unknown whether plasmids are destroyed during phage infection or released intact upon phage lysis, whereupon their encoded resistance could be acquired and manifested by other bacteria (transformation). Because phages are being developed to combat antibiotic-resistant bacteria and because transformation is a principal form of horizontal gene transfer, this question has important implications for biomedicine and microbial evolution alike. Here we report the isolation and characterization of two novel Escherichia coli phages, dubbed "superspreaders," that promote extensive plasmid transformation and efficiently disperse antibiotic resistance genes. Our work suggests that phage superspreaders are not suitable for use in medicine but may help drive bacterial evolution in natural environments.201728096488
938520.9972A generalised model for generalised transduction: the importance of co-evolution and stochasticity in phage mediated antimicrobial resistance transfer. Antimicrobial resistance is a major global challenge. Of particular concern are mobilizable elements that can transfer resistance genes between bacteria, leading to pathogens with new combinations of resistance. To date, mathematical models have largely focussed on transfer of resistance by plasmids, with fewer studies on transfer by bacteriophages. We aim to understand how best to model transfer of resistance by transduction by lytic phages. We show that models of lytic bacteriophage infection with empirically derived realistic phage parameters lead to low numbers of bacteria, which, in low population or localised environments, lead to extinction of bacteria and phage. Models that include antagonistic co-evolution of phage and bacteria produce more realistic results. Furthermore, because of these low numbers, stochastic dynamics are shown to be important, especially to spread of resistance. When resistance is introduced, resistance can sometimes be fixed, and at other times die out, with the probability of each outcome sensitive to bacterial and phage parameters. Specifically, that outcome most strongly depends on the baseline death rate of bacteria, with phage-mediated spread favoured in benign environments with low mortality over more hostile environments. We conclude that larger-scale models should consider spatial compartmentalisation and heterogeneous microenviroments, while encompassing stochasticity and co-evolution.202032490523
938930.9971Individual bacteria in structured environments rely on phenotypic resistance to phage. Bacteriophages represent an avenue to overcome the current antibiotic resistance crisis, but evolution of genetic resistance to phages remains a concern. In vitro, bacteria evolve genetic resistance, preventing phage adsorption or degrading phage DNA. In natural environments, evolved resistance is lower possibly because the spatial heterogeneity within biofilms, microcolonies, or wall populations favours phenotypic survival to lytic phages. However, it is also possible that the persistence of genetically sensitive bacteria is due to less efficient phage amplification in natural environments, the existence of refuges where bacteria can hide, and a reduced spread of resistant genotypes. Here, we monitor the interactions between individual planktonic bacteria in isolation in ephemeral refuges and bacteriophage by tracking the survival of individual cells. We find that in these transient spatial refuges, phenotypic resistance due to reduced expression of the phage receptor is a key determinant of bacterial survival. This survival strategy is in contrast with the emergence of genetic resistance in the absence of ephemeral refuges in well-mixed environments. Predictions generated via a mathematical modelling framework to track bacterial response to phages reveal that the presence of spatial refuges leads to fundamentally different population dynamics that should be considered in order to predict and manipulate the evolutionary and ecological dynamics of bacteria-phage interactions in naturally structured environments.202134637438
863040.9971Environmental fate and behaviour of antibiotic resistance genes and small interference RNAs released from genetically modified crops. Rising global populations have amplified food scarcity across the world and ushered in the development of genetically modified (GM) crops to overcome these challenges. Cultivation of major crops such as corn and soy has favoured GM crops over conventional varieties to meet crop production and resilience needs. Modern GM crops containing small interference RNA molecules and antibiotic resistance genes have become increasingly common in the United States. However, the use of these crops remains controversial due to the uncertainty regarding the unintended release of its genetic material into the environment and possible downstream effects on human and environmental health. DNA or RNA transgenes may be exuded from crop tissues during cultivation or released during plant decomposition and adsorbed by soil. This can contribute to the persistence and bioavailability in soil or water environment and possible uptake by soil microbial communities and further passing of this information to neighbouring bacteria, disrupting microbial ecosystem services such as nutrient cycling and soil fertility. In this review, transgene mechanisms of action, uses in crops, and knowledge regarding their environmental fate and impact to microbes are evaluated. This aims to encapsulate the current knowledge and promote further research regarding unintended effects transgenes may cause.202235892194
644050.9970Fate and transport of biological microcontaminants bound to microplastics in the soil environment. Microplastics, fragmented plastic particles with a maximum dimension <5 mm, are an emerging contaminant of concern that can also serve as a vector of other chemical and biological contaminants. Compared to chemical contaminants, the potential of microplastics to adsorb biological microcontaminants such as antibiotic resistance genes, small interference RNAs, and pathogenic viruses is not well understood. Many current microplastic studies are based in the aquatic environment (freshwater, seawater, and wastewater), even though the terrestrial environment is considered both an important sink and source of microplastics. Microplastics co-occur with biological microcontaminants in many terrestrial environments including agricultural soils, where biosolids containing both contaminants are often applied as a soil amendment. Recent research suggests that microplastics in these environments can increase gene persistence and flow, which could have unintended downstream consequences for environmental microbiome health and resilience. Antibiotic resistance genes and silencing RNAs bound to microplastics, for example, have the potential to increase resistance and alter gene expression in environmental bacteria, respectively. This review evaluates the sources and pathways of microplastics and biological microcontaminants in the terrestrial environment as well as potential sorption mechanisms that can encourage long-range transport and persistence. Novel sources of biological microcontaminants are considered, and the role of microplastics in promoting the persistence and flow of biological microcontaminants evaluated. Finally, future research directions are suggested to increase understanding of the mechanisms that drive the fate and transport of microplastic-biological microcontaminant complexes in the terrestrial environment and better inform risk management.202337247742
650360.9970The role of operating parameters and oxidative damage mechanisms of advanced chemical oxidation processes in the combat against antibiotic-resistant bacteria and resistance genes present in urban wastewater. An upsurge in the study of antibiotic resistance in the environment has been observed in the last decade. Nowadays, it is becoming increasingly clear that urban wastewater is a key source of antibiotic resistance determinants, i.e. antibiotic-resistant bacteria and antibiotic resistance genes (ARB&ARGs). Urban wastewater reuse has arisen as an important component of water resources management in the European Union and worldwide to address prolonged water scarcity issues. Especially, biological wastewater treatment processes (i.e. conventional activated sludge), which are widely applied in urban wastewater treatment plants, have been shown to provide an ideal environment for the evolution and spread of antibiotic resistance. The ability of advanced chemical oxidation processes (AOPs), e.g. light-driven oxidation in the presence of H(2)O(2), ozonation, homogeneous and heterogeneous photocatalysis, to inactivate ARB and remove ARGs in wastewater effluents has not been yet evaluated through a systematic and integrated approach. Consequently, this review seeks to provide an extensive and critical appraisal on the assessment of the efficiency of these processes in inactivating ARB and removing ARGs in wastewater effluents, based on recent available scientific literature. It tries to elucidate how the key operating conditions may affect the process efficiency, while pinpointing potential areas for further research and major knowledge gaps which need to be addressed. Also, this review aims at shedding light on the main oxidative damage pathways involved in the inactivation of ARB and removal of ARGs by these processes. In general, the lack and/or heterogeneity of the available scientific data, as well as the different methodological approaches applied in the various studies, make difficult the accurate evaluation of the efficiency of the processes applied. Besides the operating conditions, the variable behavior observed by the various examined genetic constituents of the microbial community, may be directed by the process distinct oxidative damage mechanisms in place during the application of each treatment technology. For example, it was shown in various studies that the majority of cellular damage by advanced chemical oxidation may be on cell wall and membrane structures of the targeted bacteria, leaving the internal components of the cells relatively intact/able to repair damage. As a result, further in-depth mechanistic studies are required, to establish the optimum operating conditions under which oxidative mechanisms target internal cell components such as genetic material and ribosomal structures more intensively, thus conferring permanent damage and/or death and preventing potential post-treatment re-growth.201829153875
648470.9969Microbial assisted phytodepuration for water reclamation: Environmental benefits and threats. Climate changes push for water reuse as a priority to counteract water scarcity and minimize water footprint especially in agriculture, one of the highest water consuming human activities. Phytodepuration is indicated as a promising technology for water reclamation, also in the light of its economic and ecological sustainability, and the use of specific bacterial inocula for microbial assisted phytodepuration has been proposed as a further advance for its implementation. Here we provided an overview on the selection and use of plant growth promoting bacteria in Constructed Wetland (CW) systems, showing their advantages in terms of plant growth support and pollutant degradation abilities. Moreover, CWs are also proposed for the removal of emerging organic pollutants like antibiotics from urban wastewaters. We focused on this issue, still debated in the literature, revealing the necessity to deepen the knowledge on the antibiotic resistance spread into the environment in relation to treated wastewater release and reuse. In addition, given the presence in the plant system of microhabitats (e.g. rhizosphere) that are hot spot for Horizontal Gene Transfer, we highlighted the importance of gene exchange to understand if these events can promote the diffusion of antibiotic resistance genes and antibiotic resistant bacteria, possibly entering in the food production chain when treated wastewater is used for irrigation. Ideally, this new knowledge will lead to improve the design of phytodepuration systems to maximize the quality and safety of the treated effluents in compliance with the 'One Health' concept.202031605997
961980.9969Phage "delay" towards enhancing bacterial escape from biofilms: a more comprehensive way of viewing resistance to bacteriophages. In exploring bacterial resistance to bacteriophages, emphasis typically is placed on those mechanisms which completely prevent phage replication. Such resistance can be detected as extensive reductions in phage ability to form plaques, that is, reduced efficiency of plating. Mechanisms include restriction-modification systems, CRISPR/Cas systems, and abortive infection systems. Alternatively, phages may be reduced in their "vigor" when infecting certain bacterial hosts, that is, with phages displaying smaller burst sizes or extended latent periods rather than being outright inactivated. It is well known, as well, that most phages poorly infect bacteria that are less metabolically active. Extracellular polymers such as biofilm matrix material also may at least slow phage penetration to bacterial surfaces. Here I suggest that such "less-robust" mechanisms of resistance to bacteriophages could serve bacteria by slowing phage propagation within bacterial biofilms, that is, delaying phage impact on multiple bacteria rather than necessarily outright preventing such impact. Related bacteria, ones that are relatively near to infected bacteria, e.g., roughly 10+ µm away, consequently may be able to escape from biofilms with greater likelihood via standard dissemination-initiating mechanisms including erosion from biofilm surfaces or seeding dispersal/central hollowing. That is, given localized areas of phage infection, so long as phage spread can be reduced in rate from initial points of contact with susceptible bacteria, then bacterial survival may be enhanced due to bacteria metaphorically "running away" to more phage-free locations. Delay mechanisms-to the extent that they are less specific in terms of what phages are targeted-collectively could represent broader bacterial strategies of phage resistance versus outright phage killing, the latter especially as require specific, evolved molecular recognition of phage presence. The potential for phage delay should be taken into account when developing protocols of phage-mediated biocontrol of biofilm bacteria, e.g., as during phage therapy of chronic bacterial infections.201731294157
968790.9969Spread of organisms with novel genotypes: thoughts from an ecological perspective. One category of objection to the release of organisms produced by genetic engineering is based on the fear that such organisms may persist in the environment and damage existing ecosystems. An assessment of environmental risk thus involves an ecological question analogous to the introduction of exotic species which has been known to produce serious ecological disruptions. An investigation of the literature on exotic introductions reveals, however, that foreign species do not invariably produce adverse changes. Ecologists believe that only a fraction of immigrating species actually produces ecological dislocation while the majority probably fail to penetrate existing biotic assemblages. Stressed or simplified environments are, however, more vulnerable to successful invasion. Unfortunately, because very little information has ever been collected to document the number or causes of failed introductions, it is impossible to quantify the probability that any introduced species will or will not cause serious disturbance purely on the basis of historical evidence. The development and spread of genotypes that confer resistance to chemical control agents in insects and microorganisms is also analogous to genetic engineering in that human activity contributes to the spread of new genotypes. In both groups of organisms, resistant genotypes can come to predominate in even geographically widespread populations with great rapidity. Resistance to pesticides in insects is usually found to be determined by single genes. In bacteria, antibiotic resistance genes are usually, if not always, associated with the extrachromosomal genetic elements known as plasmids. Bacteria seem to be able to transmit plasmid-borne genes between species and genera with facility. The ease with which new genes can be inserted into bacteria via plasmid vectors in recombinant technology is thus a two-edged sword. It may be very difficult to keep inserted genes isolated in single bacterial strains. The evaluation of the literature on which this report is based suggests that an ecological approach for risk assessment is appropriate. Microorganisms, for which genetic engineering is of most immediate importance, exhibit the same ecological properties as higher organisms. The proportion of an organism's genome which is novel has no direct correlation with the magnitude of impact such a change may have in economic, medical, or ecological terms. Meaningful probabilities for persistence of engineered organisms in the environment will have to be generated by experiment, probably with model microbial ecosystems.19836576449
6473100.9969The potential implications of reclaimed wastewater reuse for irrigation on the agricultural environment: The knowns and unknowns of the fate of antibiotics and antibiotic resistant bacteria and resistance genes - A review. The use of reclaimed wastewater (RWW) for the irrigation of crops may result in the continuous exposure of the agricultural environment to antibiotics, antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs). In recent years, certain evidence indicate that antibiotics and resistance genes may become disseminated in agricultural soils as a result of the amendment with manure and biosolids and irrigation with RWW. Antibiotic residues and other contaminants may undergo sorption/desorption and transformation processes (both biotic and abiotic), and have the potential to affect the soil microbiota. Antibiotics found in the soil pore water (bioavailable fraction) as a result of RWW irrigation may be taken up by crop plants, bioaccumulate within plant tissues and subsequently enter the food webs; potentially resulting in detrimental public health implications. It can be also hypothesized that ARGs can spread among soil and plant-associated bacteria, a fact that may have serious human health implications. The majority of studies dealing with these environmental and social challenges related with the use of RWW for irrigation were conducted under laboratory or using, somehow, controlled conditions. This critical review discusses the state of the art on the fate of antibiotics, ARB and ARGs in agricultural environment where RWW is applied for irrigation. The implications associated with the uptake of antibiotics by plants (uptake mechanisms) and the potential risks to public health are highlighted. Additionally, knowledge gaps as well as challenges and opportunities are addressed, with the aim of boosting future research towards an enhanced understanding of the fate and implications of these contaminants of emerging concern in the agricultural environment. These are key issues in a world where the increasing water scarcity and the continuous appeal of circular economy demand answers for a long-term safe use of RWW for irrigation.201728689129
9626110.9969Daphnia as a refuge for an antibiotic resistance gene in an experimental freshwater community. Mechanisms that enable the maintenance of antibiotic resistance genes in the environment are still greatly unknown. Here we show that the tetracycline resistance gene tet(A) is largely removed from the pelagic aquatic bacterial community through filter feeding by Daphnia obtusa while it becomes detectable within the microbiome of the daphniids themselves, where it was not present prior to the experiment. We moreover show that a multitude of Daphnia-associated bacterial taxa are potential carriers of tet(A) and postulated that the biofilm-like structures, where bacteria grow in, may enable horizontal transfer of such genes. This experiment highlights the need to take ecological interactions and a broad range of niches into consideration when studying and discussing the fate of antibiotic resistance genes in nature.201627459256
8344120.9969Role of environmental stresses in elevating resistance mutations in bacteria: Phenomena and mechanisms. Mutations are an important origin of antibiotic resistance in bacteria. While there is increasing evidence showing promoted resistance mutations by environmental stresses, no retrospective research has yet been conducted on this phenomenon and its mechanisms. Herein, we summarized the phenomena of stress-elevated resistance mutations in bacteria, generalized the regulatory mechanisms and discussed the environmental and human health implications. It is shown that both chemical pollutants, such as antibiotics and other pharmaceuticals, biocides, metals, nanoparticles and disinfection byproducts, and non-chemical stressors, such as ultraviolet radiation, electrical stimulation and starvation, are capable of elevating resistance mutations in bacteria. Notably, resistance mutations are more likely to occur under sublethal or subinhibitory levels of these stresses, suggesting a considerable environmental concern. Further, mechanisms for stress-induced mutations are summarized in several points, namely oxidative stress, SOS response, DNA replication and repair systems, RpoS regulon and biofilm formation, all of which are readily provoked by common environmental stresses. Given bacteria in the environment are confronted with a variety of unfavorable conditions, we propose that the stress-elevated resistance mutations are a universal phenomenon in the environment and represent a nonnegligible risk factor for ecosystems and human health. The present review identifies a need for taking into account the pollutants' ability to elevate resistance mutations when assessing their environmental and human health risks and highlights the necessity of including resistance mutations as a target to prevent antibiotic resistance evolution.202235691443
9391130.9969Bacteria-phage (co)evolution is constrained in a synthetic community across multiple bacteria-phage pairs. Bacteriophages can be important drivers of bacterial densities and, therefore, microbial community composition and function. These ecological interactions are likely to be greatly affected by evolutionary dynamics because bacteria can rapidly evolve resistance to phage, while phage can reciprocally evolve to increase infectivity. Most studies to date have explored eco-evolutionary dynamics using isolated pairs of bacteria-phage, but in nature, multiple bacteria and phages coexist and (co)evolve simultaneously. How coevolution plays out in this context is poorly understood. Here, we examine how three coexisting soil bacteria (Ochrobactrum sp., Pseudomonas sp. and Variovorax sp.) interact and evolve with three species-specific bacteriophages over 8 weeks of experimental evolution, both as host-parasite pairs in isolation and as a mixed community. Across all species, phage resistance evolution was inhibited in polyculture, with the most pronounced effect on Ochrobactrum. Between bacteria-phage pairs, there were also substantial differences in the effect of phage on host densities and evolutionary dynamics, including whether pairs coevolved. Our results also indicate bacteria have a relative advantage over phage, with high rates of phage extinction and/or lower densities in polyculture. These contrasts emphasize the difficulty in generalizing findings from monoculture to polyculture and between model bacteria-phage pairs to wider systems. Future studies should consider how multiple bacteria and phage pairs interact simultaneously to better understand how coevolutionary dynamics happen in natural communities.202540536890
8675140.9969Adaptive Strategies in a Poly-Extreme Environment: Differentiation of Vegetative Cells in Serratia ureilytica and Resistance to Extreme Conditions. Poly-extreme terrestrial habitats are often used as analogs to extra-terrestrial environments. Understanding the adaptive strategies allowing bacteria to thrive and survive under these conditions could help in our quest for extra-terrestrial planets suitable for life and understanding how life evolved in the harsh early earth conditions. A prime example of such a survival strategy is the modification of vegetative cells into resistant resting structures. These differentiated cells are often observed in response to harsh environmental conditions. The environmental strain (strain Lr5/4) belonging to Serratia ureilytica was isolated from a geothermal spring in Lirima, Atacama Desert, Chile. The Atacama Desert is the driest habitat on Earth and furthermore, due to its high altitude, it is exposed to an increased amount of UV radiation. The geothermal spring from which the strain was isolated is oligotrophic and the temperature of 54°C exceeds mesophilic conditions (15 to 45°C). Although the vegetative cells were tolerant to various environmental insults (desiccation, extreme pH, glycerol), a modified cell type was formed in response to nutrient deprivation, UV radiation and thermal shock. Scanning (SEM) and Transmission Electron Microscopy (TEM) analyses of vegetative cells and the modified cell structures were performed. In SEM, a change toward a circular shape with reduced size was observed. These circular cells possessed what appears as extra coating layers under TEM. The resistance of the modified cells was also investigated, they were resistant to wet heat, UV radiation and desiccation, while vegetative cells did not withstand any of those conditions. A phylogenomic analysis was undertaken to investigate the presence of known genes involved in dormancy in other bacterial clades. Genes related to spore-formation in Myxococcus and Firmicutes were found in S. ureilytica Lr5/4 genome; however, these genes were not enough for a full sporulation pathway that resembles either group. Although, the molecular pathway of cell differentiation in S. ureilytica Lr5/4 is not fully defined, the identified genes may contribute to the modified phenotype in the Serratia genus. Here, we show that a modified cell structure can occur as a response to extremity in a species that was previously not known to deploy this strategy. This strategy may be widely spread in bacteria, but only expressed under poly-extreme environmental conditions.201930804904
6451150.9969Antibiotic-Resistant Genes and Bacteria as Evolving Contaminants of Emerging Concerns (e-CEC): Is It Time to Include Evolution in Risk Assessment? The pressing issue of the abundance of antibiotic resistance genes and resistant bacteria in the environment (ARGs and ARB, respectively) requires procedures for assessing the risk to health. The chemo-centric environmental risk assessment models identify hazard(s) in a dose-response manner, obtaining exposure, toxicity, risk, impact and policy. However, this risk assessment approach based on ARGs/ARB evaluation from a quantitative viewpoint shows high unpredictability because ARGs/ARB cannot be considered as standard hazardous molecules: ARB duplicate and ARGs evolve within a biological host. ARGs/ARB are currently listed as Contaminants of Emerging Concern (CEC). In light of such characteristics, we propose to define ARGs/ARB within a new category of evolving CEC (or e-CEC). ARGs/ARB, like any other evolving determinants (e.g., viruses, bacteria, genes), escape environmental controls. When they do so, just one molecule left remaining at a control point can form the origin of a new dangerous and selection-responsive population. As a consequence, perhaps it is time to acknowledge this trait and to include evolutionary concepts within modern risk assessment of e-CEC. In this perspective we analyze the evolutionary responses most likely to influence risk assessment, and we speculate on the means by which current methods could measure evolution. Further work is required to implement and exploit such experimental procedures in future risk assessment protocols.202134572648
9382160.9969The evolution of mutator genes in bacterial populations: the roles of environmental change and timing. Recent studies have found high frequencies of bacteria with increased genomic rates of mutation in both clinical and laboratory populations. These observations may seem surprising in light of earlier experimental and theoretical studies. Mutator genes (genes that elevate the genomic mutation rate) are likely to induce deleterious mutations and thus suffer an indirect selective disadvantage; at the same time, bacteria carrying them can increase in frequency only by generating beneficial mutations at other loci. When clones carrying mutator genes are rare, however, these beneficial mutations are far more likely to arise in members of the much larger nonmutator population. How then can mutators become prevalent? To address this question, we develop a model of the population dynamics of bacteria confronted with ever-changing environments. Using analytical and simulation procedures, we explore the process by which initially rare mutator alleles can rise in frequency. We demonstrate that subsequent to a shift in environmental conditions, there will be relatively long periods of time during which the mutator subpopulation can produce a beneficial mutation before the ancestral subpopulations are eliminated. If the beneficial mutation arises early enough, the overall frequency of mutators will climb to a point higher than when the process began. The probability of producing a subsequent beneficial mutation will then also increase. In this manner, mutators can increase in frequency over successive selective sweeps. We discuss the implications and predictions of these theoretical results in relation to antibiotic resistance and the evolution of mutation rates.200312871898
9237170.9969The gossip paradox: Why do bacteria share genes? Bacteria, in contrast to eukaryotic cells, contain two types of genes: chromosomal genes that are fixed to the cell, and plasmids, smaller loops of DNA capable of being passed from one cell to another. The sharing of plasmid genes between individual bacteria and between bacterial lineages has contributed vastly to bacterial evolution, allowing specialized traits to 'jump ship' between one lineage or species and the next. The benefits of this generosity from the point of view of both recipient cell and plasmid are generally understood: plasmids receive new hosts and ride out selective sweeps across the population, recipient cells gain new traits (such as antibiotic resistance). Explaining this behavior from the point of view of donor cells is substantially more difficult. Donor cells pay a fitness cost in order to share plasmids, and run the risk of sharing advantageous genes with their competition and rendering their own lineage redundant, while seemingly receiving no benefit in return. Using both compartment based models and agent based simulations we demonstrate that 'secretive' genes which restrict horizontal gene transfer are favored over a wide range of models and parameter values, even when sharing carries no direct cost. 'Generous' chromosomal genes which are more permissive of plasmid transfer are found to have neutral fitness at best, and are generally disfavored by selection. Our findings lead to a peculiar paradox: given the obvious benefits of keeping secrets, why do bacteria share information so freely?202235603365
9000180.9969Modelling the synergistic effect of bacteriophage and antibiotics on bacteria: Killers and drivers of resistance evolution. Bacteriophage (phage) are bacterial predators that can also spread antimicrobial resistance (AMR) genes between bacteria by generalised transduction. Phage are often present alongside antibiotics in the environment, yet evidence of their joint killing effect on bacteria is conflicted, and the dynamics of transduction in such systems are unknown. Here, we combine in vitro data and mathematical modelling to identify conditions where phage and antibiotics act in synergy to remove bacteria or drive AMR evolution. We adapt a published model of phage-bacteria dynamics, including transduction, to add the pharmacodynamics of erythromycin and tetracycline, parameterised from new in vitro data. We simulate a system where two strains of Staphylococcus aureus are present at stationary phase, each carrying either an erythromycin or tetracycline resistance gene, and where multidrug-resistant bacteria can be generated by transduction only. We determine rates of bacterial clearance and multidrug-resistant bacteria appearance, when either or both antibiotics and phage are present at varying timings and concentrations. Although phage and antibiotics act in synergy to kill bacteria, by reducing bacterial growth antibiotics reduce phage production. A low concentration of phage introduced shortly after antibiotics fails to replicate and exert a strong killing pressure on bacteria, instead generating multidrug-resistant bacteria by transduction which are then selected for by the antibiotics. Multidrug-resistant bacteria numbers were highest when antibiotics and phage were introduced simultaneously. The interaction between phage and antibiotics leads to a trade-off between a slower clearing rate of bacteria (if antibiotics are added before phage), and a higher risk of multidrug-resistance evolution (if phage are added before antibiotics), exacerbated by low concentrations of phage or antibiotics. Our results form hypotheses to guide future experimental and clinical work on the impact of phage on AMR evolution, notably for studies of phage therapy which should investigate varying timings and concentrations of phage and antibiotics.202236449520
9627190.9968Effects of glyphosate on antibiotic resistance in soil bacteria and its potential significance: A review. The evolution and spread of antibiotic resistance are problems with important consequences for bacterial disease treatment. Antibiotic use in animal production and the subsequent export of antibiotic resistance elements in animal manure to soil is a concern. Recent reports suggest that exposure of pathogenic bacteria to glyphosate increases antibiotic resistance. We review these reports and identify soil processes likely to affect the persistence of glyphosate, antibiotic resistance elements, and their interactions. The herbicide molecular target of glyphosate is not shared by antibiotics, indicating that target-site cross-resistance cannot account for increased antibiotic resistance. The mechanisms of bacterial resistance to glyphosate and antibiotics differ, and bacterial tolerance or resistance to glyphosate does not coincide with increased resistance to antibiotics. Glyphosate in the presence of antibiotics can increase the activity of efflux pumps, which confer tolerance to glyphosate, allowing for an increased frequency of mutation for antibiotic resistance. Such effects are not unique to glyphosate, as other herbicides and chemical pollutants can have the same effect, although glyphosate is used in much larger quantities on agricultural soils than most other chemicals. Most evidence indicates that glyphosate is not mutagenic in bacteria. Some studies suggest that glyphosate enhances genetic exchange of antibiotic-resistance elements through effects on membrane permeability. Glyphosate and antibiotics are often present together in manure-treated soil for at least part of the crop-growing season, and initial studies indicate that glyphosate may increase abundance of antibiotic resistance genes in soil, but longer term investigations under realistic field conditions are needed. Although there are demonstratable interactions among glyphosate, bacteria, and antibiotic resistance, there is limited evidence that normal use of glyphosate poses a substantial risk for increased occurrence of antibiotic-resistant, bacterial pathogens. Longer term field studies using environmentally relevant concentrations of glyphosate and antibiotics are needed.202539587768