Beyond the desert sands: decoding the relationship between camels, gut microbiota, and antibiotic resistance through metagenomics. - Related Documents




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771101.0000Beyond the desert sands: decoding the relationship between camels, gut microbiota, and antibiotic resistance through metagenomics. BACKGROUND: Camels, known as the enduring "ships of the desert," host a complex gut microbiota that plays a crucial role in their survival in extreme environments. However, amidst the fascinating discoveries about the camel gut microbiota, concerns about antibiotic resistance have emerged as a significant global challenge affecting both human and animal populations. Indeed, the continued use of antibiotics in veterinary medicine has led to the widespread emergence of antibiotic-resistant bacteria, which has worsened through gene transfer. METHODS: This study offers a deeper examination of this pressing issue by harnessing the potent tools of metagenomics to explore the intricate interplay between the camel (Camelus ferus) gut microbiota and antibiotic resistance. RESULTS: Samples from wild camels yielded varying amounts of raw and clean data, generating scaftigs and open reading frames. The camel fecal microbiome was dominated by bacteria (mainly Bacillota and Bacteriodota), followed by viruses, archaea, and eukaryota. The most abundant genera were the Bacteroides, Ruminococcus, and Clostridium. Functional annotation revealed enriched pathways in metabolism, genetic information processing, and cellular processes, with key pathways involving carbohydrate transport and metabolism, replication, and amino acid transport. CAZy database analysis showed high abundances of glycoside hydrolases and glycosyl transferases. Antibiotic resistance gene (ARG) analysis identified Bacillota and Bacteroidota as the main reservoirs, with vancomycin resistance genes being the most prevalent. This study identified three major resistance mechanisms: antibiotic target alteration, antibiotic target protection, and antibiotic efflux. CONCLUSION: These findings contribute to a broader understanding of antibiotic resistance within animal microbiomes and provide a foundation for further investigations of strategies to manage and mitigate antibiotic resistance.202439763640
840910.9997Comparative genomics reveals key adaptive mechanisms in pathogen host-niche specialization. INTRODUCTION: Understanding the key factors that enable bacterial pathogens to adapt to new hosts is crucial, as host-microbe interactions not only influence host health but also drive bacterial genome diversification, thereby enhancing pathogen survival in various ecological niches. METHODS: We conducted a comparative genomic analysis of 4,366 high-quality bacterial genomes isolated from various hosts and environments. Bioinformatics databases and machine learning approaches were used to identify genomic differences in functional categories, virulence factors, and antibiotic resistance genes across different ecological niches. RESULTS: Significant variability in bacterial adaptive strategies was observed. Human-associated bacteria, particularly from the phylum Pseudomonadota, exhibited higher detection rates of carbohydrate-active enzyme genes and virulence factors related to immune modulation and adhesion, indicating co-evolution with the human host. In contrast, bacteria from environmental sources, particularly those from the phyla Bacillota and Actinomycetota, showed greater enrichment in genes related to metabolism and transcriptional regulation, highlighting their high adaptability to diverse environments. Bacteria from clinical settings had higher detection rates of antibiotic resistance genes, particularly those related to fluoroquinolone resistance. Animal hosts were identified as important reservoirs of resistance genes. Key host-specific bacterial genes, such as hypB, were found to potentially play crucial roles in regulating metabolism and immune adaptation in human-associated bacteria. DISCUSSION: These findings highlight niche-specific genomic features and adaptive mechanisms of bacterial pathogens. This study provides valuable insights into the genetic basis of host-pathogen interactions and offers evidence to inform pathogen transmission control, infection management, and antibiotic stewardship.202540547794
965720.9996Machine Learning Leveraging Genomes from Metagenomes Identifies Influential Antibiotic Resistance Genes in the Infant Gut Microbiome. Antibiotic resistance in pathogens is extensively studied, and yet little is known about how antibiotic resistance genes of typical gut bacteria influence microbiome dynamics. Here, we leveraged genomes from metagenomes to investigate how genes of the premature infant gut resistome correspond to the ability of bacteria to survive under certain environmental and clinical conditions. We found that formula feeding impacts the resistome. Random forest models corroborated by statistical tests revealed that the gut resistome of formula-fed infants is enriched in class D beta-lactamase genes. Interestingly, Clostridium difficile strains harboring this gene are at higher abundance in formula-fed infants than C. difficile strains lacking this gene. Organisms with genes for major facilitator superfamily drug efflux pumps have higher replication rates under all conditions, even in the absence of antibiotic therapy. Using a machine learning approach, we identified genes that are predictive of an organism's direction of change in relative abundance after administration of vancomycin and cephalosporin antibiotics. The most accurate results were obtained by reducing annotated genomic data to five principal components classified by boosted decision trees. Among the genes involved in predicting whether an organism increased in relative abundance after treatment are those that encode subclass B2 beta-lactamases and transcriptional regulators of vancomycin resistance. This demonstrates that machine learning applied to genome-resolved metagenomics data can identify key genes for survival after antibiotics treatment and predict how organisms in the gut microbiome will respond to antibiotic administration. IMPORTANCE The process of reconstructing genomes from environmental sequence data (genome-resolved metagenomics) allows unique insight into microbial systems. We apply this technique to investigate how the antibiotic resistance genes of bacteria affect their ability to flourish in the gut under various conditions. Our analysis reveals that strain-level selection in formula-fed infants drives enrichment of beta-lactamase genes in the gut resistome. Using genomes from metagenomes, we built a machine learning model to predict how organisms in the gut microbial community respond to perturbation by antibiotics. This may eventually have clinical applications.201829359195
768530.9996Gut heavy metal and antibiotic resistome of humans living in the high Arctic. Contaminants, such as heavy metals (HMs), accumulate in the Arctic environment and the food web. The diet of the Indigenous Peoples of North Greenland includes locally sourced foods that are central to their nutritional, cultural, and societal health but these foods also contain high concentrations of heavy metals. While bacteria play an essential role in the metabolism of xenobiotics, there are limited studies on the impact of heavy metals on the human gut microbiome, and it is so far unknown if and how Arctic environmental contaminants impact the gut microbes of humans living in and off the Arctic environment. Using a multiomics approach including amplicon, metagenome, and metatranscriptome sequencing, we identified and assembled a near-complete (NC) genome of a mercury-resistant bacterial strain from the human gut microbiome, which expressed genes known to reduce mercury toxicity. At the overall ecological level studied through α- and β-diversity, there was no significant effect of heavy metals on the gut microbiota. Through the assembly of a high number of NC metagenome-assembled genomes (MAGs) of human gut microbes, we observed an almost complete overlap between heavy metal-resistant strains and antibiotic-resistant strains in which resistance genes were all located on the same genetic elements.202439539714
768140.9996Amoebae contribute to the diversity and fate of antibiotic resistance genes in drinking water system. Free-living amoebae represent a significant eukaryotic group that thrives in drinking water systems, posing considerable risks to water quality due to their inherent pathogenicity and associations with various microorganisms. However, the symbiotic microbial profiles of different amoeba species and the impact of amoeba-bacteria interactions on the antibiotic resistome within drinking water systems remain poorly understood. In this study, we obtained 24 amoeba isolates from tap water, encompassing diverse phyla within the amoeba lineage. Through metagenome sequencing, we uncovered variations in symbiotic microbiome composition across different amoeba species and strains. Notably, amoebae acted as vectors for human pathogens, including bacteria and viruses. The majority of symbionts carried multiple antibiotic-resistance genes and virulence factors. Furthermore, dominant symbiotic species could be cultured independently, underscoring the critical role of amoebae in preserving and transmitting antibiotic-resistant opportunistic pathogens in drinking water systems. Disinfection experiments demonstrated highly diverse viability of amoebae and their protective capabilities for symbionts against chlorine disinfection. Our findings expand the germplasm bank for amoebae and symbiotic bacteria derived from tap water and emphasize the necessity for further research on amoeba-bacteria symbiosis to ensure drinking water quality and public health safety.202541101029
964850.9996The highly diverse Antarctic Peninsula soil microbiota as a source of novel resistance genes. The rise of multiresistant bacterial pathogens is currently one of the most critical threats to global health, encouraging a better understanding of the evolution and spread of antimicrobial resistance. In this regard, the role of the environment as a source of resistance mechanisms remains poorly understood. Moreover, we still know a minimal part of the microbial diversity and resistome present in remote and extreme environments, hosting microbes that evolved to resist harsh conditions and thus a potentially rich source of novel resistance genes. This work demonstrated that the Antarctic Peninsula soils host a remarkable microbial diversity and a widespread presence of autochthonous antibiotic-resistant bacteria and resistance genes. We observed resistance to a wide array of antibiotics among isolates, including Pseudomonas resisting ten or more different compounds, with an overall increased resistance in bacteria from non-intervened areas. In addition, genome analysis of selected isolates showed several genes encoding efflux pumps, as well as a lack of known resistance genes for some of the resisted antibiotics, including colistin, suggesting novel uncharacterized mechanisms. By combining metagenomic approaches based on analyzing raw reads, assembled contigs, and metagenome-assembled genomes, we found hundreds of widely distributed genes potentially conferring resistance to different antibiotics (including an outstanding variety of inactivation enzymes), metals, and biocides, hosted mainly by Polaromonas, Pseudomonas, Streptomyces, Variovorax, and Burkholderia. Furthermore, a proportion of these genes were found inside predicted plasmids and other mobile elements, including a putative OXA-like carbapenemase from Polaromonas harboring conserved key residues and predicted structural features. All this evidence indicates that the Antarctic Peninsula soil microbiota has a broad natural resistome, part of which could be transferred horizontally to pathogenic bacteria, acting as a potential source of novel resistance genes.202234856283
769160.9996Antimicrobial Chemicals Associate with Microbial Function and Antibiotic Resistance Indoors. Humans purposefully and inadvertently introduce antimicrobial chemicals into buildings, resulting in widespread compounds, including triclosan, triclocarban, and parabens, in indoor dust. Meanwhile, drug-resistant infections continue to increase, raising concerns that buildings function as reservoirs of, or even select for, resistant microorganisms. Support for these hypotheses is limited largely since data describing relationships between antimicrobials and indoor microbial communities are scant. We combined liquid chromatography-isotope dilution tandem mass spectrometry with metagenomic shotgun sequencing of dust collected from athletic facilities to characterize relationships between indoor antimicrobial chemicals and microbial communities. Elevated levels of triclosan and triclocarban, but not parabens, were associated with distinct indoor microbiomes. Dust of high triclosan content contained increased Gram-positive species with diverse drug resistance capabilities, whose pangenomes were enriched for genes encoding osmotic stress responses, efflux pump regulation, lipid metabolism, and material transport across cell membranes; such triclosan-associated functional shifts have been documented in laboratory cultures but not yet from buildings. Antibiotic-resistant bacterial isolates were cultured from all but one facility, and resistance often increased in buildings with very high triclosan levels, suggesting links between human encounters with viable drug-resistant bacteria and local biocide conditions. This characterization uncovers complex relationships between antimicrobials and indoor microbiomes: some chemicals elicit effects, whereas others may not, and no single functional or resistance factor explained chemical-microbe associations. These results suggest that anthropogenic chemicals impact microbial systems in or around buildings and their occupants, highlighting an emergent need to identify the most important indoor, outdoor, and host-associated sources of antimicrobial chemical-resistome interactions. IMPORTANCE The ubiquitous use of antimicrobial chemicals may have undesired consequences, particularly on microbes in buildings. This study shows that the taxonomy and function of microbes in indoor dust are strongly associated with antimicrobial chemicals-more so than any other feature of the buildings. Moreover, we identified links between antimicrobial chemical concentrations in dust and culturable bacteria that are cross-resistant to three clinically relevant antibiotics. These findings suggest that humans may be influencing the microbial species and genes that are found indoors through the addition and removal of particular antimicrobial chemicals.201830574558
428170.9996Investigating RND efflux pumps in Sphingobium yanoikuyae P4: the role of nonpathogenic bacteria in antibiotic resistance gene spread amid environmental contamination. The widespread and inappropriate application of antibiotics across human and veterinary medicine has generated pressing global health threats, principally the emergence of antimicrobial resistance (AMR) and the contamination of the environment with antibiotics. A fundamental mechanism fueling environmental AMR is the proliferation and horizontal dissemination of antibiotic resistance genes (ARGs), with efflux transporter proteins functioning as central intermediaries. Surprisingly, nonpathogenic bacteria, which are usually regarded as harmless, now pose a substantial risk to society due to the presence of efflux transporters, which make them AMR contributors. In this study, the genomic analysis of the nonpathogenic soil bacterium Sphingobium yanoikuyae P4 revealed an RND (Resistance-Nodulation-Division) efflux pump containing the relevant domains responsible for antibiotic efflux. Molecular docking studies revealed high affinities between the efflux pump and various antibiotics, including fluoroquinolones, beta-lactams, and sulfonamides, raising the possibility of their efflux into the environment. Antibiotic susceptibility tests showed reduced susceptibility due to the action of this efflux transporter. Furthermore, the genome analysis suggested the presence of mobile genetic elements and plasmid-associated sequences, indicating possible horizontal gene transfer. The data highlights that both nonpathogenic and pathogenic bacteria are crucial for capturing and transmitting antibiotic-resistance genes. These results confirm the disregard for existing concerns over the substantial role of nonpathogenic environmental bacteria in the ecological resistome and warrant the need to consider such microorganisms in monitoring and controlling AMR.202540737558
769480.9996The Human Gut Resistome up to Extreme Longevity. Antibiotic resistance (AR) is indisputably a major health threat which has drawn much attention in recent years. In particular, the gut microbiome has been shown to act as a pool of AR genes, potentially available to be transferred to opportunistic pathogens. Herein, we investigated for the first time changes in the human gut resistome during aging, up to extreme longevity, by analyzing shotgun metagenomics data of fecal samples from a geographically defined cohort of 62 urban individuals, stratified into four age groups: young adults, elderly, centenarians, and semisupercentenarians, i.e., individuals aged up to 109 years. According to our findings, some AR genes are similarly represented in all subjects regardless of age, potentially forming part of the core resistome. Interestingly, aging was found to be associated with a higher burden of some AR genes, including especially proteobacterial genes encoding multidrug efflux pumps. Our results warn of possible health implications and pave the way for further investigations aimed at containing AR accumulation, with the ultimate goal of promoting healthy aging. IMPORTANCE Antibiotic resistance is widespread among different ecosystems, and in humans it plays a key role in shaping the composition of the gut microbiota, enhancing the ecological fitness of certain bacterial populations when exposed to antibiotics. A considerable component of the definition of healthy aging and longevity is associated with the structure of the gut microbiota, and, in this regard, the presence of antibiotic-resistant bacteria is critical to many pathologies that come about with aging. However, the structure of the resistome has not yet been sufficiently elucidated. Here, we show distinct antibiotic resistance assets and specific microbial consortia characterizing the human gut resistome through aging.202134494880
966090.9996Interkingdom Gut Microbiome and Resistome of the Cockroach Blattella germanica. Cockroaches are intriguing animals with two coexisting symbiotic systems, an endosymbiont in the fat body, involved in nitrogen metabolism, and a gut microbiome whose diversity, complexity, role, and developmental dynamics have not been fully elucidated. In this work, we present a metagenomic approach to study Blattella germanica populations not treated, treated with kanamycin, and recovered after treatment, both naturally and by adding feces to the diet, with the aim of better understanding the structure and function of its gut microbiome along the development as well as the characterization of its resistome.IMPORTANCE For the first time, we analyze the interkingdom hindgut microbiome of this species, including bacteria, fungi, archaea, and viruses. Network analysis reveals putative cooperation between core bacteria that could be key for ecosystem equilibrium. We also show how antibiotic treatments alter microbiota diversity and function, while both features are restored after one untreated generation. Combining data from B. germanica treated with three antibiotics, we have characterized this species' resistome. It includes genes involved in resistance to several broad-spectrum antibiotics frequently used in the clinic. The presence of genetic elements involved in DNA mobilization indicates that they can be transferred among microbiota partners. Therefore, cockroaches can be considered reservoirs of antibiotic resistance genes (ARGs) and potential transmission vectors.202133975971
5101100.9996Identification of Key Features Pivotal to the Characteristics and Functions of Gut Bacteria Taxa through Machine Learning Methods. BACKGROUND: Gut bacteria critically influence digestion, facilitate the breakdown of complex food substances, aid in essential nutrient synthesis, and contribute to immune system balance. However, current knowledge regarding intestinal bacteria remains insufficient. OBJECTIVE: This study aims to discover essential differences for different intestinal bacteria. METHODS: This study was conducted by investigating a total of 1478 gut bacterial samples comprising 235 Actinobacteria, 447 Bacteroidetes, and 796 Firmicutes, by utilizing sophisticated machine learning algorithms. By building on the dataset provided by Chen et al., we engaged sophisticated machine learning techniques to further investigate and analyze the gut bacterial samples. Each sample in the dataset was described by 993 unique features associated with gut bacteria, including 342 features annotated by the Antibiotic Resistance Genes Database, Comprehensive Antibiotic Research Database, Kyoto Encyclopedia of Genes and Genomes, and Virulence Factors of Pathogenic Bacteria. We employed incremental feature selection methods within a computational framework to identify the optimal features for classification. RESULTS: Eleven feature ranking algorithms selected several key features as pivotal to the characteristics and functions of gut bacteria. These features appear to facilitate the identification of specific gut bacterial species. Additionally, we established quantitative rules for identifying Actinobacteria, Bacteroidetes, and Firmicutes. CONCLUSION: This research underscores the significant potential of machine learning in studying gut microbes and enhances our understanding of the multifaceted roles of gut bacteria.202540671232
7684110.9996Trophic level and proteobacteria abundance drive antibiotic resistance levels in fish from coastal New England. BACKGROUND: The natural marine environment represents a vast reservoir of antimicrobial resistant bacteria. The wildlife that inhabits this environment plays an important role as the host to these bacteria and in the dissemination of resistance. The relationship between host diet, phylogeny, and trophic level and the microbiome/resistome in marine fish is not fully understood. To further explore this relationship, we utilize shotgun metagenomic sequencing to define the gastrointestinal tract microbiomes of seven different marine vertebrates collected in coastal New England waters. RESULTS: We identify inter and intraspecies differences in the gut microbiota of these wild marine fish populations. Furthermore, we find an association between antibiotic resistance genes and host dietary guild, which suggests that higher trophic level organisms have a greater abundance of resistance genes. Additionally, we demonstrate that antibiotic resistance gene burden is positively correlated with Proteobacteria abundance in the microbiome. Lastly, we identify dietary signatures within the gut of these fish and find evidence of possible dietary selection for bacteria with specific carbohydrate utilization potential. CONCLUSIONS: This work establishes a link between host lifestyle/dietary guild, and microbiome composition and the abundance of antibiotic resistance genes within the gastrointestinal tract of marine organisms. We expand the current understanding of marine organism-associated microbial communities and their role as reservoirs of antimicrobial resistance genes.202336879316
7682120.9996Soil Amoebae Are Unexpected Hotspots of Environmental Antibiotics and Antibiotic Resistance Genes. Antibiotic resistance poses a significant threat to human health. While most studies focus on bacteria, interactions between antibiotics and other crucial microbial groups like protists remain uncertain. This study investigates how protists interact with antibiotics and examines how these interactions impact the fate of resistance genes. It reveals that amoebae exhibit high resistance to eight high-risk environmental antibiotics, accumulating significant quantities within their cells. Wild amoeboid strains from distant locations carry substantial antibiotic resistance genes (ARGs) and metal resistance genes (MRGs), with significant heterogeneity within a single species. Amoeboid symbionts and pathogens predominantly carry these genes. Paraburkholderia symbionts have reduced genomes and fewer resistance genes compared to free-living strains, while amoeba-endogenous Stenotrophomonas maltophilia does not exhibit a significantly reduced genome size. This suggests that the amoeboid hosts serve as a temporary medium facilitating its transmission. In summary, the study unveils that soil amoebae represent unexpected hotspots for antibiotics and resistance genes. Future research should assess the effects of antibiotics on often-overlooked protists and explore their role in spreading ARGs and MRGs in ecosystems. Incorporating protists into broader antibiotic resistance research is recommended, highlighting their significance within a One Health perspective.202439584452
9729130.9996Omics technology draws a comprehensive heavy metal resistance strategy in bacteria. The rapid industrial revolution significantly increased heavy metal pollution, becoming a major global environmental concern. This pollution is considered as one of the most harmful and toxic threats to all environmental components (air, soil, water, animals, and plants until reaching to human). Therefore, scientists try to find a promising and eco-friendly technique to solve this problem i.e., bacterial bioremediation. Various heavy metal resistance mechanisms were reported. Omics technologies can significantly improve our understanding of heavy metal resistant bacteria and their communities. They are a potent tool for investigating the adaptation processes of microbes in severe conditions. These omics methods provide unique benefits for investigating metabolic alterations, microbial diversity, and mechanisms of resistance of individual strains or communities to harsh conditions. Starting with genome sequencing which provides us with complete and comprehensive insight into the resistance mechanism of heavy metal resistant bacteria. Moreover, genome sequencing facilitates the opportunities to identify specific metal resistance genes, operons, and regulatory elements in the genomes of individual bacteria, understand the genetic mechanisms and variations responsible for heavy metal resistance within and between bacterial species in addition to the transcriptome, proteome that obtain the real expressed genes. Moreover, at the community level, metagenome, meta transcriptome and meta proteome participate in understanding the microbial interactive network potentially novel metabolic pathways, enzymes and gene species can all be found using these methods. This review presents the state of the art and anticipated developments in the use of omics technologies in the investigation of microbes used for heavy metal bioremediation.202438709343
7704140.9996Temporal 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
7714150.9996Functional traits and health implications of the global household drinking-water microbiome retrieved using an integrative genome-centric approach. The biological safety of drinking water plays a crucial role in public health protection. However, research on the drinking water microbiome remains in its infancy, especially little is known about the potentially pathogenic bacteria in and functional characteristics of the microbiome in household tap water that people are directly exposed to. In this study, we used a genomic-centric approach to construct a genetic catalogue of the drinking water microbiome by analysing 116 metagenomic datasets of household tap water worldwide, spanning nine countries/regions on five continents. We reconstructed 859 high-quality metagenome-assembled genomes (MAGs) spanning 27 bacterial and 2 archaeal phyla, and found that the core MAGs belonging to the phylum Proteobacteria encoded the highest metabolic functional diversity of the 33 key complete metabolic modules. In particular, we found that two core MAGs of Brevibacillus and Methylomona encoded genes for methane metabolism, which may support the growth of heterotrophic organisms observed in the oligotrophic ecosystem. Four MAGs of complete ammonia oxidation (comammox) Nitrospira were identified and functional metabolic analysis suggested these may enable mixotrophic growth and encode genes for reactive oxygen stress defence and arsenite reduction that could aid survival in the environment of oligotrophic drinking water systems. Four MAGs were annotated as potentially pathogenic bacteria (PPB) and thus represented a possible public health concern. They belonged to the genera Acinetobacter (n = 3) and Mycobacterium (n = 1), with a total relative abundance of 1.06 % in all samples. The genomes of PPB A. junii and A. ursingii were discovered to contain antibiotic resistance genes and mobile genetic elements that could contribute to antimicrobial dissemination in drinking water. Further network analysis suggested that symbiotic microbes which support the growth of pathogenic bacteria can be targets for future surveillance and removal.202438183799
7690160.9996Novel Antibiotic Resistance Determinants from Agricultural Soil Exposed to Antibiotics Widely Used in Human Medicine and Animal Farming. Antibiotic resistance has emerged globally as one of the biggest threats to human and animal health. Although the excessive use of antibiotics is recognized as accelerating the selection for resistance, there is a growing body of evidence suggesting that natural environments are "hot spots" for the development of both ancient and contemporary resistance mechanisms. Given that pharmaceuticals can be entrained onto agricultural land through anthropogenic activities, this could be a potential driver for the emergence and dissemination of resistance in soil bacteria. Using functional metagenomics, we interrogated the "resistome" of bacterial communities found in a collection of Canadian agricultural soil, some of which had been receiving antibiotics widely used in human medicine (macrolides) or food animal production (sulfamethazine, chlortetracycline, and tylosin) for up to 16 years. Of the 34 new antibiotic resistance genes (ARGs) recovered, the majority were predicted to encode (multi)drug efflux systems, while a few share little to no homology with established resistance determinants. We characterized several novel gene products, including putative enzymes that can confer high-level resistance against aminoglycosides, sulfonamides, and broad range of beta-lactams, with respect to their resistance mechanisms and clinical significance. By coupling high-resolution proteomics analysis with functional metagenomics, we discovered an unusual peptide, PPP(AZI 4), encoded within an alternative open reading frame not predicted by bioinformatics tools. Expression of the proline-rich PPP(AZI 4) can promote resistance against different macrolides but not other ribosome-targeting antibiotics, implicating a new macrolide-specific resistance mechanism that could be fundamentally linked to the evolutionary design of this peptide.IMPORTANCE Antibiotic resistance is a clinical phenomenon with an evolutionary link to the microbial pangenome. Genes and protogenes encoding specialized and potential resistance mechanisms are abundant in natural environments, but understanding of their identity and genomic context remains limited. Our discovery of several previously unknown antibiotic resistance genes from uncultured soil microorganisms indicates that soil is a significant reservoir of resistance determinants, which, once acquired and "repurposed" by pathogenic bacteria, can have serious impacts on therapeutic outcomes. This study provides valuable insights into the diversity and identity of resistance within the soil microbiome. The finding of a novel peptide-mediated resistance mechanism involving an unpredicted gene product also highlights the usefulness of integrating proteomics analysis into metagenomics-driven gene discovery.201728625995
7689170.9996Discovery of Novel Antibiotic Resistance Determinants in Forest and Grassland Soil Metagenomes. Soil represents a significant reservoir of antibiotic resistance genes (ARGs), which can potentially spread across distinct ecosystems and be acquired by pathogens threatening human as well as animal health. Currently, information on the identity and diversity of these genes, enabling anticipation of possible future resistance development in clinical environments and the livestock sector, is lacking. In this study, we applied functional metagenomics to discover novel sulfonamide as well as tetracycline resistance genes in soils derived from forest and grassland. Screening of soil metagenomic libraries revealed a total of eight so far unknown ARGs. The recovered genes originate from phylogenetically diverse soil bacteria (e.g., Actinobacteria, Chloroflexi, or Proteobacteria) and encode proteins with a minimum identity of 46% to other antibiotic resistance determinants. In particular forest soil ecosystems have so far been neglected in studies focusing on antibiotic resistance. Here, we detected for the first time non-mobile dihydropteroate synthase (DHPS) genes conferring resistance to sulfonamides in forest soil with no history of exposure to these synthetic drugs. In total, three sulfonamide resistant DHPSs, differing in taxonomic origin, were discovered in beech or pine forest soil. This indicates that sulfonamide resistance naturally occurs in forest-resident soil bacterial communities. Besides forest soil-derived sulfonamide resistance proteins, we also identified a DHPS affiliated to Chloroflexi in grassland soil. This enzyme and the other recovered DHPSs confer reduced susceptibility toward sulfamethazine, which is widely used in food animal production. With respect to tetracycline resistance, four efflux proteins affiliated to the major facilitator superfamily (MFS) were identified. Noteworthy, one of these proteins also conferred reduced susceptibility toward lincomycin.201930899254
7712180.9996Metagenomic analysis of microbial communities and antibiotic resistance genes in spoiled household chemicals. Numerous attempts have been utilized to unveil the occurrences of antibiotic resistance genes (ARGs) in human-associated and non-human-associated samples. However, spoiled household chemicals, which are usually neglected by the public, may be also a reservoir of ARGs because of the excessive and inappropriate uses of industrial drugs. Based upon the Comprehensive Antibiotic Research Database, a metagenomic sequencing method was utilized to detect and quantify Antibiotic Resistance Ontology (AROs) in six spoiled household chemicals, including hair conditioner, dishwashing detergent, bath shampoo, hand sanitizer, and laundry detergent. Proteobacteria was found to be the dominant phylum in all the samples. Functional annotation of the unigenes obtained against the KEGG pathway, eggNOG and CAZy databases demonstrated a diversity of their functions. Moreover, 186 types of AROs that were members of 72 drug classes were identified. Multidrug resistance genes were the most dominant types, and there were 17 AROs whose resistance mechanisms were categorized into the resistance-nodulation-cell division antibiotic efflux pump among the top 20 AROs. Moreover, Proteobacteria was the dominant carrier of AROs with the primary resistance mechanism of antibiotic efflux. The maximum temperature of the months of collection significantly affected the distributions of AROs. Additionally, the isolated individual bacterium from spoiled household chemicals and artificial mixed communities of isolated bacteria demonstrated diverse resistant abilities to different biocides. This study demonstrated that there are abundant microorganisms and a broad spectrum profile of AROs in spoiled household chemicals that might induce a severe threat to public healthy securities and merit particular attention.202234740703
8410190.9996Unveiling the role of phages in shaping the periodontal microbial ecosystem. The oral microbiome comprises various species and plays a crucial role in maintaining the oral ecosystem and host health. Phages are an important component of the periodontal microbiome, yet our understanding of periodontal phages remains limited. Here, we investigated oral periodontal phages using various advanced bioinformatics tools based on genomes of key periodontitis pathogens. Prophages were found to encode various auxiliary genes that potentially enhance host survival and pathogenicity, including genes involved in carbohydrate metabolism, antibiotic resistance, and immune modulation. We observed cross-species transmission among prophages with a complex network of phage-bacteria interactions. Our findings suggest that prophages play a crucial role in shaping the periodontal microbial ecosystem, influencing microbial community dynamics and the progression of periodontitis.IMPORTANCEIn the context of periodontitis, the ecological dynamics of the microbiome are largely driven by interactions between bacteria and their phages. While the impact of prophages on regulating oral pathogens has been increasingly recognized, their role in modulating periodontal disease remains underexplored. This study reveals that prophages within key periodontitis pathogens contribute significantly to virulence factor dissemination, antibiotic resistance, and host metabolism. By influencing the metabolic capabilities and survival strategies of their bacterial hosts, prophages may act as critical regulators of microbial communities in the oral cavity. Understanding these prophage-mediated interactions is essential not only for unraveling the mechanisms of periodontal disease progression but also for developing innovative therapeutic approaches that target the microbial ecosystem at the genetic level. These insights emphasize the need for more comprehensive studies on the ecological risks posed by prophages in shaping microbial pathogenicity and resistance.202540152610