A metagenomic analysis for combination therapy of multiple classes of antibiotics on the prevention of the spread of antibiotic-resistant genes. - Related Documents




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770201.0000A metagenomic analysis for combination therapy of multiple classes of antibiotics on the prevention of the spread of antibiotic-resistant genes. Antibiotics used systemically to treat infections may have off-target effects on the gut microbiome, potentially resulting in the emergence of drug-resistant bacteria or selection of pathogenic species. These organisms may present a risk to the host and spread to the environment with a risk of transmission in the community. To investigate the risk of emergent antibiotic resistance in the gut microbiome following systemic treatment with antibiotics, this metagenomic analysis project used next-generation sequencing, a custom-built metagenomics pipeline, and differential abundance analysis to study the effect of antibiotics (ampicillin, ciprofloxacin, and fosfomycin) in monotherapy and different combinations at high and low doses, to determine the effect on resistome and taxonomic composition in the gut of Balb/c mice. The results showed that low-dose monotherapy treatments showed little change in microbiome composition but did show an increase in expression of many antibiotic-resistant genes (ARGs) posttreatment. Dual combination treatments allowed the emergence of some conditionally pathogenic bacteria and some increase in the abundance of ARGs despite a general decrease in microbiota diversity. Triple combination treatment was the most successful in inhibiting emergence of relevant opportunistic pathogens and completely suppressed all ARGs after 72 h of treatment. The relative abundances of mobile genetic elements that can enhance transmission of antibiotic resistance either decreased or remained the same for combination therapy while increasing for low-dose monotherapy. Combination therapy prevented the emergence of ARGs and decreased bacterial diversity, while low-dose monotherapy treatment increased ARGs and did not greatly change bacterial diversity.202337908118
325710.9999The effect of antibiotics on the gut microbiome: a metagenomics analysis of microbial shift and gut antibiotic resistance in antibiotic treated mice. BACKGROUND: Emergence of antibiotic resistance is a global public health concern. The relationships between antibiotic use, the gut community composition, normal physiology and metabolism, and individual and public health are still being defined. Shifts in composition of bacteria, antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs) after antibiotic treatment are not well-understood. METHODS: This project used next-generation sequencing, custom-built metagenomics pipeline and differential abundance analysis to study the effect of antibiotic monotherapy on resistome and taxonomic composition in the gut of Balb/c mice infected with E. coli via transurethral catheterization to investigate the evolution and emergence of antibiotic resistance. RESULTS: There is a longitudinal decrease of gut microbiota diversity after antibiotic treatment. Various ARGs are enriched within the gut microbiota despite an overall reduction of the diversity and total amount of bacteria after antibiotic treatment. Sometimes treatment with a specific class of antibiotics selected for ARGs that resist antibiotics of a completely different class (e.g. treatment of ciprofloxacin or fosfomycin selected for cepA that resists ampicillin). Relative abundance of some MGEs increased substantially after antibiotic treatment (e.g. transposases in the ciprofloxacin group). CONCLUSIONS: Antibiotic treatment caused a remarkable reduction in diversity of gut bacterial microbiota but enrichment of certain types of ARGs and MGEs. These results demonstrate an emergence of cross-resistance as well as a profound change in the gut resistome following oral treatment of antibiotics.202032228448
770120.9999Elucidating selection processes for antibiotic resistance in sewage treatment plants using metagenomics. Sewage treatment plants (STPs) have repeatedly been suggested as "hotspots" for the emergence and dissemination of antibiotic-resistant bacteria. A critical question still unanswered is if selection pressures within STPs, caused by residual antibiotics or other co-selective agents, are sufficient to specifically promote resistance. To address this, we employed shotgun metagenomic sequencing of samples from different steps of the treatment process in three Swedish STPs. In parallel, concentrations of selected antibiotics, biocides and metals were analyzed. We found that concentrations of tetracycline and ciprofloxacin in the influent were above predicted concentrations for resistance selection, however, there was no consistent enrichment of resistance genes to any particular class of antibiotics in the STPs, neither for biocide and metal resistance genes. The most substantial change of the bacterial communities compared to human feces occurred already in the sewage pipes, manifested by a strong shift from obligate to facultative anaerobes. Through the treatment process, resistance genes against antibiotics, biocides and metals were not reduced to the same extent as fecal bacteria. The OXA-48 gene was consistently enriched in surplus and digested sludge. We find this worrying as OXA-48, still rare in Swedish clinical isolates, provides resistance to carbapenems, one of our most critically important classes of antibiotics. Taken together, metagenomics analyses did not provide clear support for specific antibiotic resistance selection. However, stronger selective forces affecting gross taxonomic composition, and with that resistance gene abundances, limit interpretability. Comprehensive analyses of resistant/non-resistant strains within relevant species are therefore warranted.201627542633
762530.9999Antimicrobial peptides: An alternative to antibiotic for mitigating the risks of Antibiotic resistance in aquaculture. The utilization of antibiotics increases the prevalence of antibiotic resistance genes (ARGs) in various matrices and poses the potential risk of ARG transmission, garnering global attention. Antimicrobial peptides (AMPs) represent a promising novel category of antimicrobials that may address the urgent issue of antibiotic resistance. Here, a zebrafish cultivation assay in which zebrafish were fed a diet supplemented with AMP (Cecropin A) or antibiotics was conducted to determine the effects of the intervention on the microorganisms and antibiotic resistance spectrum in zebrafish gut samples. Cecropin A treatment decreased the α-diversity of the microbiota. Moreover, NMDS (nonmetric multidimensional scaling) results revealed that the β-diversity in the microbiota was more similar between the control (CK) and Cecropin A samples than between the antibiotic treatment groups. The absolute quantity of ARGs in the AMP treatment was less than that observed in the antibiotic treatment. The findings indicated that FFCH7168, Chitinibacter and Cetobacterium were the most significant biomarkers detected in the CK, Cecropin A and antibiotic treatments, respectively. Although the use of antibiotics notably enhanced the occurrence of multidrug-resistant bacteria, the application of Cecropin A did not lead to this phenomenon. The results indicated that the application of AMPs can effectively manage and control ARGs in aquaculture.202438442817
770340.9998The impact of antibiotic exposure on antibiotic resistance gene dynamics in the gut microbiota of inflammatory bowel disease patients. BACKGROUND: While antibiotics are commonly used to treat inflammatory bowel disease (IBD), their widespread application can disturb the gut microbiota and foster the emergence and spread of antibiotic resistance. However, the dynamic changes to the human gut microbiota and direction of resistance gene transmission under antibiotic effects have not been clearly elucidated. METHODS: Based on the Human Microbiome Project, a total of 90 fecal samples were collected from 30 IBD patients before, during and after antibiotic treatment. Through the analysis workflow of metagenomics, we described the dynamic process of changes in bacterial communities and resistance genes pre-treatment, during and post-treatment. We explored potential consistent relationships between gut microbiota and resistance genes, and established gene transmission networks among species before and after antibiotic use. RESULTS: Exposure to antibiotics can induce alterations in the composition of the gut microbiota in IBD patients, particularly a reduction in probiotics, which gradually recovers to a new steady state after cessation of antibiotics. Network analyses revealed intra-phylum transfers of resistance genes, predominantly between taxonomically close organisms. Specific resistance genes showed increased prevalence and inter-species mobility after antibiotic cessation. CONCLUSION: This study demonstrates that antibiotics shape the gut resistome through selective enrichment and promotion of horizontal gene transfer. The findings provide insights into ecological processes governing resistance gene dynamics and dissemination upon antibiotic perturbation of the microbiota. Optimizing antibiotic usage may help limit unintended consequences like increased resistance in gut bacteria during IBD management.202438694799
962950.9998Costs of antibiotic resistance genes depend on host strain and environment and can influence community composition. Antibiotic resistance genes (ARGs) benefit host bacteria in environments containing corresponding antibiotics, but it is less clear how they are maintained in environments where antibiotic selection is weak or sporadic. In particular, few studies have measured if the direct effect of ARGs on host fitness is fixed or if it depends on the host strain, perhaps marking some ARG-host combinations as selective refuges that can maintain ARGs in the absence of antibiotic selection. We quantified the fitness effects of six ARGs in 11 diverse Escherichia spp. strains. Three ARGs (bla(TEM-116), cat and dfrA5, encoding resistance to β-lactams, chloramphenicol, and trimethoprim, respectively) imposed an overall cost, but all ARGs had an effect in at least one host strain, reflecting a significant strain interaction effect. A simulation predicts these interactions can cause the success of ARGs to depend on available host strains, and, to a lesser extent, can cause host strain success to depend on the ARGs present in a community. These results indicate the importance of considering ARG effects across different host strains, and especially the potential of refuge strains to allow resistance to persist in the absence of direct selection, in efforts to understand resistance dynamics.202438889784
742960.9998Industrial wastewater treatment plant enriches antibiotic resistance genes and alters the structure of microbial communities. Antibiotic resistance is an emerging global health crisis, driven largely by overuse and misuse of antibiotics. However, there are examples in which the production of these antimicrobial agents has polluted the environment with active antibiotic residues, selecting for antibiotic resistant bacteria and the genes they carry. In this work, we have used shotgun metagenomics to investigate the taxonomic structure and resistance gene composition of sludge communities in a treatment plant in Croatia receiving wastewater from production of the macrolide antibiotic azithromycin. We found that the total abundance of antibiotic resistance genes was three times higher in sludge from the treatment plant receiving wastewater from pharmaceutical production than in municipal sludge from a sewage treatment plant in Zagreb. Surprisingly, macrolide resistance genes did not have higher abundances in the industrial sludge, but genes associated with mobile genetic elements such as integrons had. We conclude that at high concentrations of antibiotics, selection may favor taxonomic shifts towards intrinsically resistant species or strains harboring chromosomal resistance mutations rather than acquisition of mobile resistance determinants. Our results underscore the need for regulatory action also within Europe to avoid release of antibiotics into the environment.201931301473
385970.9998Co-selection of antibiotic resistance via copper shock loading on bacteria from a drinking water bio-filter. Heavy metal contamination of source water frequently occurred in developing countries as a result of accidents. To address the problems, most of the previous studies have focused on engineering countermeasures. In this study, we investigated the effects of heavy metals, particularly copper, on the development of antibiotic resistance by establishing a copper shock loading test. Results revealed that co-selection occurred rapidly within 6 h. Copper, at the levels of 10 and 100 mg/L, significantly increased bacterial resistance to the antibiotics tested, including rifampin, erythromycin, kanamycin, and a few others. A total of 117 antimicrobial-resistance genes were detected from 12 types of genes, and the relative abundance of most genes (particularly mobile genetic elements intⅠand transposons) was markedly enriched by at least one fold. Furthermore, the copper shock loading altered the bacterial community. Numerous heavy metal and antibiotic resistant strains were screened out and enriched. These strains are expected to enhance the overall level of resistance. More noticeably, the majority of the co-selected antibiotic resistance could sustain for at least 20 h in the absence of copper and antimicrobial drugs. Resistance to vancomycin, erythromycin and lincomycin even could remain for 7 days. The prominent selection pressure by the copper shock loading implies that a real accident most likely poses similar impacts on the water environment. An accidental release of heavy metals would not only cause harm to the ecological environment, but also contribute to the development of bacterial antibiotic resistance. Broader concerns should be raised about the biological risks caused by sudden releases of pollutants by accidents.201829059628
386280.9998Interaction of tetracycline and copper co-intake in inducing antibiotic resistance genes and potential pathogens in mouse gut. The widespread use of copper and tetracycline as growth promoters in the breeding industry poses a potential threat to environmental health. Nevertheless, to the best of our knowledge, the potential adverse effects of copper and tetracycline on the gut microbiota remain unknown. Herein, mice were fed different concentrations of copper and/or tetracycline for 6 weeks to simulate real life-like exposure in the breeding industry. Following the exposure, antibiotic resistance genes (ARGs), potential pathogens, and other pathogenic factors were analyzed in mouse feces. The co-exposure of copper with tetracycline significantly increased the abundance of ARGs and enriched more potential pathogens in the gut of the co-treated mice. Copper and/or tetracycline exposure increased the abundance of bacteria carrying either ARGs, metal resistance genes, or virulence factors, contributing to the widespread dissemination of potentially harmful genes posing a severe risk to public health. Our study provides insights into the effects of copper and tetracycline exposure on the gut resistome and potential pathogens, and our findings can help reduce the risks associated with antibiotic resistance under the One Health framework.202438527398
738590.9998Soil-specific responses in the antibiotic resistome of culturable Acinetobacter spp. and other non-fermentative Gram-negative bacteria following experimental manure application. Acinetobacter spp. and other non-fermenting Gram-negative bacteria (NFGNB) represent an important group of opportunistic pathogens due to their propensity for multiple, intrinsic, or acquired antimicrobial resistance (AMR). Antimicrobial resistant bacteria and their genes can spread to the environment through livestock manure. This study investigated the effects of fresh manure from dairy cows under antibiotic prophylaxis on the antibiotic resistome and AMR hosts in microcosms using pasture soil. We specifically focused on culturable Acinetobacter spp. and other NFGNB using CHROMagar Acinetobacter. We conducted two 28-days incubation experiments to simulate natural deposition of fresh manure on pasture soil and evaluated the effects on antibiotic resistance genes (ARGs) and bacterial hosts through shotgun metagenomics. We found that manure application altered the abundance and composition of ARGs and their bacterial hosts, and that the effects depended on the soil source. Manure enriched the antibiotic resistome of bacteria only in the soil where native bacteria had a low abundance of ARGs. Our study highlights the role of native soil bacteria in modulating the consequences of manure deposition on soil and confirms the potential of culturable Acinetobacter spp. and other NFGNB to accumulate AMR in pasture soil receiving fresh manure.202337977851
4127100.9998The Perfect Condition for the Rising of Superbugs: Person-to-Person Contact and Antibiotic Use Are the Key Factors Responsible for the Positive Correlation between Antibiotic Resistance Gene Diversity and Virulence Gene Diversity in Human Metagenomes. Human metagenomes with a high diversity of virulence genes tend to have a high diversity of antibiotic-resistance genes and vice-versa. To understand this positive correlation, we simulated the transfer of these genes and bacterial pathogens in a community of interacting people that take antibiotics when infected by pathogens. Simulations show that people with higher diversity of virulence and resistance genes took antibiotics long ago, not recently. On the other extreme, we find people with low diversity of both gene types because they took antibiotics recently-while antibiotics select specific resistance genes, they also decrease gene diversity by eliminating bacteria. In general, the diversity of virulence and resistance genes becomes positively correlated whenever the transmission probability between people is higher than the probability of losing resistance genes. The positive correlation holds even under changes of several variables, such as the relative or total diversity of virulence and resistance genes, the contamination probability between individuals, the loss rate of resistance genes, or the social network type. Because the loss rate of resistance genes may be shallow, we conclude that the transmission between people and antibiotic usage are the leading causes for the positive correlation between virulence and antibiotic-resistance genes.202134065307
3256110.9998Co-localization of antibiotic resistance genes is widespread in the infant gut microbiome and associates with an immature gut microbial composition. BACKGROUND: In environmental bacteria, the selective advantage of antibiotic resistance genes (ARGs) can be increased through co-localization with genes such as other ARGs, biocide resistance genes, metal resistance genes, and virulence genes (VGs). The gut microbiome of infants has been shown to contain numerous ARGs, however, co-localization related to ARGs is unknown during early life despite frequent exposures to biocides and metals from an early age. RESULTS: We conducted a comprehensive analysis of genetic co-localization of resistance genes in a cohort of 662 Danish children and examined the association between such co-localization and environmental factors as well as gut microbial maturation. Our study showed that co-localization of ARGs with other resistance and virulence genes is common in the early gut microbiome and is associated with gut bacteria that are indicative of low maturity. Statistical models showed that co-localization occurred mainly in the phylum Proteobacteria independent of high ARG content and contig length. We evaluated the stochasticity of co-localization occurrence using enrichment scores. The most common forms of co-localization involved tetracycline and fluoroquinolone resistance genes, and, on plasmids, co-localization predominantly occurred in the form of class 1 integrons. Antibiotic use caused a short-term increase in mobile ARGs, while non-mobile ARGs showed no significant change. Finally, we found that a high abundance of VGs was associated with low gut microbial maturity and that VGs showed even higher potential for mobility than ARGs. CONCLUSIONS: We found that the phenomenon of co-localization between ARGs and other resistance and VGs was prevalent in the gut at the beginning of life. It reveals the diversity that sustains antibiotic resistance and therefore indirectly emphasizes the need to apply caution in the use of antimicrobial agents in clinical practice, animal husbandry, and daily life to mitigate the escalation of resistance. Video Abstract.202438730321
7405120.9998Microbial Diversity and Antimicrobial Resistance Profile in Microbiota From Soils of Conventional and Organic Farming Systems. Soil is one of the biggest reservoirs of microbial diversity, yet the processes that define the community dynamics are not fully understood. Apart from soil management being vital for agricultural purposes, it is also considered a favorable environment for the evolution and development of antimicrobial resistance, which is due to its high complexity and ongoing competition between the microorganisms. Different approaches to agricultural production might have specific outcomes for soil microbial community composition and antibiotic resistance phenotype. Therefore in this study we aimed to compare the soil microbiota and its resistome in conventional and organic farming systems that are continually influenced by the different treatment (inorganic fertilizers and pesticides vs. organic manure and no chemical pest management). The comparison of the soil microbial communities revealed no major differences among the main phyla of bacteria between the two farming styles with similar soil structure and pH. Only small differences between the lower taxa could be observed indicating that the soil community is stable, with minor shifts in composition being able to handle the different styles of treatment and fertilization. It is still unclear what level of intensity can change microbial composition but current conventional farming in Central Europe demonstrates acceptable level of intensity for soil bacterial communities. When the resistome of the soils was assessed by screening the total soil DNA for clinically relevant and soil-derived antibiotic resistance genes, a low variety of resistance determinants was detected (resistance to β-lactams, aminoglycosides, tetracycline, erythromycin, and rifampicin) with no clear preference for the soil farming type. The same soil samples were also used to isolate antibiotic resistant cultivable bacteria, which were predominated by highly resistant isolates of Pseudomonas, Stenotrophomonas, Sphingobacterium and Chryseobacterium genera. The resistance of these isolates was largely dependent on the efflux mechanisms, the soil Pseudomonas spp. relying mostly on RND, while Stenotrophomonas spp. and Chryseobacterium spp. on RND and ABC transporters.201931105678
7705130.9998Oxytetracycline reduces the diversity of tetracycline-resistance genes in the Galleria mellonella gut microbiome. BACKGROUND: Clinically-relevant multidrug resistance is sometimes present in bacteria not exposed to human-made antibiotics, in environments without extreme selective pressures, such as the insect gut. The use of antibiotics on naïve microbiomes often leads to decreased microbe diversity and increased antibiotic resistance. RESULTS: Here we investigate the impact of antibiotics on the insect gut microbiome by identifying tetracycline-resistance genes in the gut bacteria of greater wax moth (Galleria mellonella) larvae, feeding on artificial food containing oxytetracycline. We determined that G. mellonella can be raised on artificial food for over five generations and that the insects tolerate low doses of antibiotics in their diets, but doses of oxytetracycline higher than sub-inhibitory lead to early larval mortality. In our experiments, greater wax moth larvae had a sparse microbiome, which is consistent with previous findings. Additionally, we determined that the microbiome of G. mellonella larvae not exposed to antibiotics carries a number of tetracycline-resistance genes and some of that diversity is lost upon exposure to strong selective pressure. CONCLUSIONS: We show that G. mellonella larvae can be raised on artificial food, including antibiotics, for several generations and that the microbiome can be sampled. We show that, in the absence of antibiotics, the insect gut microbiome can maintain a diverse pool of tetracycline-resistance genes. Selective pressure, from exposure to the antibiotic oxytetracycline, leads to microbiome changes and alteration in the tetracycline-resistance gene pool.201830594143
7388140.9998Poultry manure-derived microorganisms as a reservoir and source of antibiotic resistance genes transferred to soil autochthonous microorganisms. Animal husbandry is increasing yearly due to the growing demand for meat and livestock products, among other reasons. To meet these demands, prophylactic antibiotics are used in the livestock industry (i.e., poultry farming) to promote health and stimulate animal growth. However, antibiotics are not fully metabolized by animals, and they are evacuated to the environment with excreta. Animal manure is used as fertilizer to reduce the volume of waste generated in the livestock sector. However, manure often contains microorganisms harboring antibiotic resistance genes (ARGs). Then, the microbiome of manure applicate to the soil may contribute to the spread of antibiotic resistance in the environment, including autochthonous soil-dwelling microorganisms. The present study was conducted during the crops growing season in Poland (May to September 2019) to determine the influence of poultry manure as well as poultry manure supplemented with selected antibiotics on the diversity of the soil microbiome in treatments that had not been previously fertilized with manure and the ability of antibiotic-resistant bacteria to transfer ARGs to other soil bacteria. Antibiotic concentrations were elevated at the beginning of the study and decreased over time. Poultry manure induced significant changes in the structure of microbial communities in soil; the diversity of the soil microbiome decreased, and the abundance of bacterial genera Bradyrhizobium, Streptomyces, and Pseudomonas, which are characteristic of the analyzed manure, increased. Over time, soil microbial diversity was restored to the state observed before the application of manure. Genes conferring resistance to multiple drugs as well as genes encoding resistance to bacitracin and aminoglycosides were the most frequently identified ARGs in the analyzed bacteria, including on mobile genetic elements. Multidrug resistance was observed in 17 bacterial taxa, whereas ARGs were identified in 32 bacterial taxa identified in the soil microbiome. The results of the study conclude that the application of poultry manure supplemented with antibiotics initially affects soil microbiome and resistome diversity but finally, the soil shows resilience and returns to its original state after time, with most antibiotic resistance genes disappearing. This phenomenon is of great importance in sustainable soil health after manure application.202337832303
3997150.9998Pyrosequencing of antibiotic-contaminated river sediments reveals high levels of resistance and gene transfer elements. The high and sometimes inappropriate use of antibiotics has accelerated the development of antibiotic resistance, creating a major challenge for the sustainable treatment of infections world-wide. Bacterial communities often respond to antibiotic selection pressure by acquiring resistance genes, i.e. mobile genetic elements that can be shared horizontally between species. Environmental microbial communities maintain diverse collections of resistance genes, which can be mobilized into pathogenic bacteria. Recently, exceptional environmental releases of antibiotics have been documented, but the effects on the promotion of resistance genes and the potential for horizontal gene transfer have yet received limited attention. In this study, we have used culture-independent shotgun metagenomics to investigate microbial communities in river sediments exposed to waste water from the production of antibiotics in India. Our analysis identified very high levels of several classes of resistance genes as well as elements for horizontal gene transfer, including integrons, transposons and plasmids. In addition, two abundant previously uncharacterized resistance plasmids were identified. The results suggest that antibiotic contamination plays a role in the promotion of resistance genes and their mobilization from environmental microbes to other species and eventually to human pathogens. The entire life-cycle of antibiotic substances, both before, under and after usage, should therefore be considered to fully evaluate their role in the promotion of resistance.201121359229
9630160.9998Novel Insights into Selection for Antibiotic Resistance in Complex Microbial Communities. Recent research has demonstrated that selection for antibiotic resistance occurs at very low antibiotic concentrations in single-species experiments, but the relevance of these findings when species are embedded in complex microbial communities is unclear. We show that the strength of selection for naturally occurring resistance alleles in a complex community remains constant from low subinhibitory to above clinically relevant concentrations. Selection increases with antibiotic concentration before reaching a plateau where selection remains constant over a 2-order-magnitude concentration range. This is likely to be due to cross protection of the susceptible bacteria in the community following rapid extracellular antibiotic degradation by the resistant population, shown experimentally through a combination of chemical quantification and bacterial growth experiments. Metagenome and 16S rRNA analyses of sewage-derived bacterial communities evolved under cefotaxime exposure show preferential enrichment for bla(CTX-M) genes over all other beta-lactamase genes, as well as positive selection and co-selection for antibiotic resistant, opportunistic pathogens. These findings have far-reaching implications for our understanding of the evolution of antibiotic resistance, by challenging the long-standing assumption that selection occurs in a dose-dependent manner.IMPORTANCE Antibiotic resistance is one of the greatest global issues facing society. Still, comparatively little is known about selection for resistance at very low antibiotic concentrations. We show that the strength of selection for clinically important resistance genes within a complex bacterial community can remain constant across a large antibiotic concentration range (wide selective space). Therefore, largely understudied ecological compartments could be just as important as clinical environments for selection of antibiotic resistance.201830042197
7471170.9998Impact of fluoroquinolone and heavy metal pollution on antibiotic resistance maintenance in aquatic ecosystems. BACKGROUND: Freshwater pollution with compounds used during anthropogenic activities could be a major driver of antibiotic resistance emergence and dissemination in environmental settings. Fluoroquinolones and heavy metals are two widely used aquatic pollutants that show a high stability in the environment and have well-known effects on antibiotic resistance selection. However, the impact of these compounds on antibiotic resistance maintenance in aquatic ecosystems remains unknown. In this study, we used a microcosm approach to determine the persistence of two fluoroquinolones (ciprofloxacin, ofloxacin) and two heavy metals (copper and zinc) in the Rhône river over 27 days. In addition, we established links between antibiotic and metal pollution, alone and in combination, and the composition of freshwater bacterial communities, the selection of specific members and the selection and maintenance of antibiotic and metal resistance genes (ARGs and MRGs) using a metagenomics approach. RESULTS: Whereas ofloxacin was detected at higher levels in freshwater after 27 days, copper had the strongest influence on bacterial communities and antibiotic and metal resistance gene selection. In addition, heavy metal exposure selected for some ARG-harboring bacteria that contained MRGs. Our research shows a heavy metal-driven transient co-selection for fluoroquinolone resistance in an aquatic ecosystem that could be largely explained by the short-term selection of Pseudomonas subpopulations harboring both fluoroquinolone efflux pumps and copper resistance genes. CONCLUSION: This research highlights the complexity and compound-specificity of dose-response relationships in freshwater ecosystems and provides new insights into the medium-term community structure modifications induced by overall sub-inhibitory levels of antibiotic and heavy metal pollution that may lead to the selection and maintenance of antibiotic resistance in low-impacted ecosystems exposed to multiple pollutants.202540426239
7427180.9998A Review of Antibiotics, Antibiotic Resistant Bacteria, and Resistance Genes in Aquaculture: Occurrence, Contamination, and Transmission. Antibiotics are commonly used to prevent and control diseases in aquaculture. However, long-term/overuse of antibiotics not only leaves residues but results in the development of antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs). Antibiotics, ARB, and ARGs are widespread in aquaculture ecosystems. However, their impacts and interaction mechanisms in biotic and abiotic media remain to be clarified. In this paper, we summarized the detection methods, present status, and transfer mechanisms of antibiotics, ARB, and ARGs in water, sediment, and aquaculture organisms. Currently, the dominant methods of detecting antibiotics, ARB, and ARGs are UPLC-MS/MS, 16S rRNA sequencing, and metagenomics, respectively. Tetracyclines, macrolides, fluoroquinolones, and sulfonamides are most frequently detected in aquaculture. Generally, antibiotic concentrations and ARG abundance in sediment are much higher than those in water. Yet, no obvious patterns in the category of antibiotics or ARB are present in organisms or the environment. The key mechanisms of resistance to antibiotics in bacteria include reducing the cell membrane permeability, enhancing antibiotic efflux, and structural changes in antibiotic target proteins. Moreover, horizontal transfer is a major pathway for ARGs transfer, including conjugation, transformation, transduction, and vesiculation. Identifying, quantifying, and summarizing the interactions and transmission mechanisms of antibiotics, ARGs, and ARB would provide useful information for future disease diagnosis and scientific management in aquaculture.202337235235
7704190.9998Temporal development and potential interactions between the gut microbiome and resistome in early childhood. Antimicrobial resistance-associated infections have become a major threat to global health. The gut microbiome serves as a major reservoir of bacteria with antibiotic resistance genes; whereas, the temporal development of gut resistome during early childhood and the factors influencing it remain unclear. Moreover, the potential interactions between gut microbiome and resistome still need to be further explored. In this study, we found that antibiotic treatment led to destabilization of the gut microbiome and resistome structural communities, exhibiting a greater impact on the resistome than on the microbiome. The composition of the gut resistome at various developmental stages was influenced by the abundance and richness of different core microbes. First exposure to antibiotics led to a dramatic increase in the number of opportunistic pathogens carrying multidrug efflux pump encoding genes. Multiple factors could influence the gut microbiome and resistome formation. The data may provide new insights into early-life research.IMPORTANCEIn recent years, the irrational or inappropriate use of antibiotics, an important life-saving medical intervention, has led to the emergence and increase of drug-resistant and even multidrug-resistant bacteria. It remains unclear how antibiotic exposure affects various developmental stages of early childhood and how gut core microbes under antibiotic exposure affect the structural composition of the gut resistome. In this study, we focused on early antibiotic exposure and analyzed these questions in detail using samples from infants at various developmental stages. The significance of our research is to elucidate the impact of early antibiotic exposure on the dynamic patterns of the gut resistome in children and to provide new insights for early-life studies.202438193687