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511700.9043Metagenomic sequencing of mpox virus clade Ib lesions identifies possible bacterial and viral co-infections in hospitalized patients in eastern DRC. Mpox is an emerging zoonotic disease that caused two public health emergencies of international concern within two years. Less is known about the interplay of microbial organisms in mpox lesions which could result in superinfections that exacerbate outcomes or delay recovery. We utilized a unified metagenomic sequencing approach involving slow-speed centrifugation and differential lysis on 19 mpox lesion swabs of hospitalized patients in South Kivu province (eastern DRC) to characterize bacteria, antimicrobial resistance genes, mpox virus (MPXV), and viral co-infections. High-quality MPXV whole-genome sequences were obtained until a Ct value of 27. Furthermore, co-infections with other clinically relevant viruses, such as varicella zoster virus and herpes simplex virus-2, were detected and confirmed by real-time PCR. In addition, metagenomic sequence analysis of the bacterial content showed the presence of bacteria associated with skin and soft tissue infection in 10 of the 19 samples analyzed. These bacteria had a high abundance of resistance genes, with possible implications for antimicrobial treatment based on the predicted antimicrobial resistance. In conclusion, we report the presence of bacterial and viral pathogens in mpox lesions and detection of widespread resistance genes to the standard antibiotic treatment. The possibility of a co-infection, including antimicrobial resistance, should be considered when discussing treatment options, along with the determination of the case-fatality ratio.IMPORTANCEThe mpox virus clade Ib lineage emerged in the eastern Democratic Republic of the Congo owing to continuous human-to-human transmission in a vulnerable patient population. A major challenge of this ongoing outbreak is its occurrence in regions with severely limited healthcare infrastructure. As a result, less is known about co-infections in affected patients. Identifying and characterizing pathogens, including their antimicrobial resistance, is crucial for reducing infection-related complications and improving antimicrobial stewardship. In this study, we applied a unified metagenomics approach to detect and characterize bacterial and viral co-infections in mpox lesions of hospitalized mpox patients in the eastern DRC.202540445195
511810.8965Automated extraction of genes associated with antibiotic resistance from the biomedical literature. The detection of bacterial antibiotic resistance phenotypes is important when carrying out clinical decisions for patient treatment. Conventional phenotypic testing involves culturing bacteria which requires a significant amount of time and work. Whole-genome sequencing is emerging as a fast alternative to resistance prediction, by considering the presence/absence of certain genes. A lot of research has focused on determining which bacterial genes cause antibiotic resistance and efforts are being made to consolidate these facts in knowledge bases (KBs). KBs are usually manually curated by domain experts to be of the highest quality. However, this limits the pace at which new facts are added. Automated relation extraction of gene-antibiotic resistance relations from the biomedical literature is one solution that can simplify the curation process. This paper reports on the development of a text mining pipeline that takes in English biomedical abstracts and outputs genes that are predicted to cause resistance to antibiotics. To test the generalisability of this pipeline it was then applied to predict genes associated with Helicobacter pylori antibiotic resistance, that are not present in common antibiotic resistance KBs or publications studying H. pylori. These genes would be candidates for further lab-based antibiotic research and inclusion in these KBs. For relation extraction, state-of-the-art deep learning models were used. These models were trained on a newly developed silver corpus which was generated by distant supervision of abstracts using the facts obtained from KBs. The top performing model was superior to a co-occurrence model, achieving a recall of 95%, a precision of 60% and F1-score of 74% on a manually annotated holdout dataset. To our knowledge, this project was the first attempt at developing a complete text mining pipeline that incorporates deep learning models to extract gene-antibiotic resistance relations from the literature. Additional related data can be found at https://github.com/AndreBrincat/Gene-Antibiotic-Resistance-Relation-Extraction.202235134132
259020.8949Combining stool and stories: exploring antimicrobial resistance among a longitudinal cohort of international health students. BACKGROUND: Antimicrobial resistance (AMR) is a global public health concern that requires transdisciplinary and bio-social approaches. Despite the continuous calls for a transdisciplinary understanding of this problem, there is still a lack of such studies. While microbiology generates knowledge about the biomedical nature of bacteria, social science explores various social practices related to the acquisition and spread of these bacteria. However, the two fields remain disconnected in both methodological and conceptual levels. Focusing on the acquisition of multidrug resistance genes, encoding extended-spectrum betalactamases (CTX-M) and carbapenemases (NDM-1) among a travelling population of health students, this article proposes a methodology of 'stool and stories' that combines methods of microbiology and sociology, thus proposing a way forward to a collaborative understanding of AMR. METHODS: A longitudinal study with 64 health students travelling to India was conducted in 2017. The study included multiple-choice questionnaires (n = 64); a collection of faecal swabs before travel (T0, n = 45), in the first week in India (T1, n = 44), the second week in India (T2, n = 41); and semi-structured interviews (n = 11). Stool samples were analysed by a targeted metagenomic approach. Data from semi-structured interviews were analysed using the method of thematic analysis. RESULTS: The incidence of ESBL- and carbapenemase resistance genes significantly increased during travel indicating it as a potential risk; for CTX-M from 11% before travel to 78% during travel and for NDM-1 from 2% before travel to 11% during travel. The data from semi-structured interviews showed that participants considered AMR mainly in relation to individual antibiotic use or its presence in a clinical environment but not to travelling. CONCLUSION: The microbiological analysis confirmed previous research showing that international human mobility is a risk factor for AMR acquisition. However, sociological methods demonstrated that travellers understand AMR primarily as a clinical problem and do not connect it to travelling. These findings indicate an important gap in understanding AMR as a bio-social problem raising a question about the potential effectiveness of biologically driven AMR stewardship programs among travellers. Further development of the 'stool and stories' approach is important for a transdisciplinary basis of AMR stewardship.202134579656
249530.8948Transmission of Mobile Colistin Resistance (mcr-1) by Duodenoscope. BACKGROUND: Clinicians increasingly utilize polymyxins for treatment of serious infections caused by multidrug-resistant gram-negative bacteria. Emergence of plasmid-mediated, mobile colistin resistance genes creates potential for rapid spread of polymyxin resistance. We investigated the possible transmission of Klebsiella pneumoniae carrying mcr-1 via duodenoscope and report the first documented healthcare transmission of mcr-1-harboring bacteria in the United States. METHODS: A field investigation, including screening targeted high-risk groups, evaluation of the duodenoscope, and genome sequencing of isolated organisms, was conducted. The study site included a tertiary care academic health center in Boston, Massachusetts, and extended to community locations in New England. RESULTS: Two patients had highly related mcr-1-positive K. pneumoniae isolated from clinical cultures; a duodenoscope was the only identified epidemiological link. Screening tests for mcr-1 in 20 healthcare contacts and 2 household contacts were negative. Klebsiella pneumoniae and Escherichia coli were recovered from the duodenoscope; neither carried mcr-1. Evaluation of the duodenoscope identified intrusion of biomaterial under the sealed distal cap; devices were recalled to repair this defect. CONCLUSIONS: We identified transmission of mcr-1 in a United States acute care hospital that likely occurred via duodenoscope despite no identifiable breaches in reprocessing or infection control practices. Duodenoscope design flaws leading to transmission of multidrug-resistant organsisms persist despite recent initiatives to improve device safety. Reliable detection of colistin resistance is currently challenging for clinical laboratories, particularly given the absence of a US Food and Drug Administration-cleared test; improved clinical laboratory capacity for colistin susceptibility testing is needed to prevent the spread of mcr-carrying bacteria in healthcare settings.201930204838
664840.8948Multi-Drug Resistant Coliform: Water Sanitary Standards and Health Hazards. Water constitutes and sustains life; however, its pollution afflicts its necessity, further worsening its scarcity. Coliform is one of the largest groups of bacteria evident in fecally polluted water, a major public health concern. Coliform thrive as commensals in the gut of warm-blooded animals, and are indefinitely passed through their feces into the environment. They are also called as model organisms as their presence is indicative of the prevalence of other potential pathogens, thus coliform are and unanimously employed as adept indicators of fecal pollution. As only a limited accessible source of fresh water is available on the planet, its contamination severely affects its usability. Coliform densities vary geographically and seasonally which leads to the lack of universally uniform regulatory guidelines regarding water potability often leads to ineffective detection of these model organisms and the misinterpretation of water quality status. Remedial measures such as disinfection, reducing the nutrient concentration or re-population doesn't hold context in huge lotic ecosystems such as freshwater rivers. There is also an escalating concern regarding the prevalence of multi-drug resistance in coliforms which renders antibiotic therapy incompetent. Antimicrobials are increasingly used in household, clinical, veterinary, animal husbandry and agricultural settings. Sub-optimal concentrations of these antimicrobials are unintentionally but regularly dispensed into the environment through seepages, sewages or runoffs from clinical or agricultural settings substantially adding to the ever-increasing pool of antibiotic resistance genes. When present below their minimum inhibitory concentration (MIC), these antimicrobials trigger the transfer of antibiotic-resistant genes that the coliform readily assimilate and further propagate to pathogens, the severity of which is evidenced by the high Multiple Antibiotic Resistance (MAR) index shown by the bacterial isolates procured from the environmental. This review attempts to assiduously anthologize the use of coliforms as water quality standards, their existent methods of detection and the issue of arising multi-drug resistance in them.201829946253
664950.8945 The development of antibiotics has provided much success against infectious diseases in animals and humans. But the intensive and extensive use of antibiotics over the years has resulted in the emergence of drug-resistant bacterial pathogens. The existence of a reservoir(s) of antibiotic resistant bacteria and antibiotic resistance genes in an interactive environment of animals, plants, and humans provides the opportunity for further transfer and dissemination of antibiotic resistance. The emergence of antibiotic resistant bacteria has created growing concern about its impact on animal and human health. To specifically address the impact of antibiotic resistance resulting from the use of antibiotics in agriculture, the American Academy of Microbiology convened a colloquium, “Antibiotic Resistance and the Role of Antimicrobials in Agriculture: A Critical Scientific Assessment,” in Santa Fe, New Mexico, November 2–4, 2001. Colloquium participants included academic, industrial, and government researchers with a wide range of expertise, including veterinary medicine, microbiology, food science, pharmacology, and ecology. These scientists were asked to provide their expert opinions on the current status of antibiotic usage and antibiotic resistance, current research information, and provide recommendations for future research needs. The research areas to be addressed were roughly categorized under the following areas: ▪ Origins and reservoirs of resistance; ▪ Transfer of resistance; ▪ Overcoming/modulating resistance by altering usage; and ▪ Interrupting transfer of resistance. The consensus of colloquium participants was that the evaluation of antibiotic usage and its impact were complex and subject to much speculation and polarization. Part of the complexity stems from the diverse array of animals and production practices for food animal production. The overwhelming consensus was that any use of antibiotics creates the possibility for the development of antibiotic resistance, and that there already exist pools of antibiotic resistance genes and antibiotic resistant bacteria. Much discussion revolved around the measurement of antibiotic usage, the measurement of antibiotic resistance, and the ability to evaluate the impact of various types of usage (animal, human) on overall antibiotic resistance. Additionally, many participants identified commensal bacteria as having a possible role in the continuance of antibiotic resistance as reservoirs. Participants agreed that many of the research questions could not be answered completely because of their complexity and the need for better technologies. The concept of the “smoking gun” to indicate that a specific animal source was important in the emergence of certain antibiotic resistant pathogens was discussed, and it was agreed that ascribing ultimate responsibility is likely to be impossible. There was agreement that expanded and more improved surveillance would add to current knowledge. Science-based risk assessments would provide better direction in the future. As far as preventive or intervention activities, colloquium participants reiterated the need for judicious/prudent use guidelines. Yet they also emphasized the need for better dissemination and incorporation by end-users. It is essential that there are studies to measure the impact of educational efforts on antibiotic usage. Other recommendations included alternatives to antibiotics, such as commonly mentioned vaccines and probiotics. There also was an emphasis on management or production practices that might decrease the need for antibiotics. Participants also stressed the need to train new researchers and to interest students in postdoctoral work, through training grants, periodic workshops, and comprehensive conferences. This would provide the expertise needed to address these difficult issues in the future. Finally, the participants noted that scientific societies and professional organizations should play a pivotal role in providing technical advice, distilling and disseminating information to scientists, media, and consumers, and in increasing the visibility and funding for these important issues. The overall conclusion is that antibiotic resistance remains a complex issue with no simple answers. This reinforces the messages from other meetings. The recommendations from this colloquium provide some insightful directions for future research and action.200232687288
306960.8944The hospital sink drain biofilm resistome is independent of the corresponding microbiota, the environment and disinfection measures. In hospitals, the transmission of antibiotic-resistant bacteria (ARB) may occur via biofilms present in sink drains, which can lead to infections. Despite the potential role of sink drains in the transmission of ARB in nosocomial infections, routine surveillance of these drains is lacking in most hospitals. As a result, there is currently no comprehensive understanding of the transmission of ARB and the dissemination of antimicrobial resistance genes (ARGs) and associated mobile genetic elements (MGEs) via sink drains. This study employed a multifaceted approach to monitor the total aerobic bacteria as well as the presence of carbapenemase-producing Enterobacterales (CPEs), the microbiota and the resistome of sink drain biofilms (SDBs) and hospital wastewater (WW) of two separate intensive care units (ICUs) in the same healthcare facility in France. Samples of SDB and WW were collected on a monthly basis, from January to April 2023, in the neonatal (NICU) and the adult (AICU) ICUs of Grenoble Alpes University Hospital. In the NICU, sink drain disinfection with surfactants was performed routinely. In the AICU, routine disinfection is not carried out. Culturable aerobic bacteria were quantified on non-selective media, and CPEs were screened using two selective agars. Isolates were identified by MALDI-TOF MS, and antibiotic susceptibility testing (AST) was performed on Enterobacterales and P. aeruginosa. The resistome was analyzed by high-throughput qPCR targeting >80 ARGs and MGEs. The overall bacterial microbiota was assessed via full-length 16S rRNA sequencing. No CPEs were isolated from SDBs in either ICU by bacterial culture. Culture-independent approaches revealed an overall distinct microbiota composition of the SDBs in the two ICUs. The AICU SDBs were dominated by pathogens containing Gram-negative bacterial genera including Pseudomonas, Stenotrophomona, Klebsiella, and Gram-positive Staphylococcus, while the NICU SDBs were dominated by the Gram-negative genera Achromobacter, Serratia, and Acidovorax, as well as the Gram-positive genera Weisella and Lactiplantibacillus. In contrast, the resistome of the SDBs exhibited no significant differences between the two ICUs, indicating that the abundance of ARGs and MGEs is independent of microbiota composition and disinfection practices. The AICU WW exhibited more distinct aerobic bacteria than the NICU WW. In addition, the AICU WW yielded 15 CPEs, whereas the NICU WW yielded a single CPE. All the CPEs were characterized at the species level. The microbiota of the NICU and AICU WW samples differed from their respective SDBs and exhibited distinct variations over the four-month period:the AICU WW contained a greater number of genes conferring resistance to quinolones and integron integrase genes, whereas the NICU WW exhibited a higher abundance of streptogramin resistance genes. Our study demonstrated that the resistome of the hospital SDBs in the two ICUs of the investigated healthcare institute is independent of the microbiota, the environment, and the local disinfection measures. However, the prevalence of CPEs in the WW pipes collecting the waste from the investigated drains differed. These findings offer valuable insights into the resilience of resistance genes in SDBs in ICUs, underscoring the necessity for innovative strategies to combat antimicrobial resistance in clinical environments.202540483807
908370.8943ARGNet: using deep neural networks for robust identification and classification of antibiotic resistance genes from sequences. BACKGROUND: Emergence of antibiotic resistance in bacteria is an important threat to global health. Antibiotic resistance genes (ARGs) are some of the key components to define bacterial resistance and their spread in different environments. Identification of ARGs, particularly from high-throughput sequencing data of the specimens, is the state-of-the-art method for comprehensively monitoring their spread and evolution. Current computational methods to identify ARGs mainly rely on alignment-based sequence similarities with known ARGs. Such approaches are limited by choice of reference databases and may potentially miss novel ARGs. The similarity thresholds are usually simple and could not accommodate variations across different gene families and regions. It is also difficult to scale up when sequence data are increasing. RESULTS: In this study, we developed ARGNet, a deep neural network that incorporates an unsupervised learning autoencoder model to identify ARGs and a multiclass classification convolutional neural network to classify ARGs that do not depend on sequence alignment. This approach enables a more efficient discovery of both known and novel ARGs. ARGNet accepts both amino acid and nucleotide sequences of variable lengths, from partial (30-50 aa; 100-150 nt) sequences to full-length protein or genes, allowing its application in both target sequencing and metagenomic sequencing. Our performance evaluation showed that ARGNet outperformed other deep learning models including DeepARG and HMD-ARG in most of the application scenarios especially quasi-negative test and the analysis of prediction consistency with phylogenetic tree. ARGNet has a reduced inference runtime by up to 57% relative to DeepARG. CONCLUSIONS: ARGNet is flexible, efficient, and accurate at predicting a broad range of ARGs from the sequencing data. ARGNet is freely available at https://github.com/id-bioinfo/ARGNet , with an online service provided at https://ARGNet.hku.hk . Video Abstract.202438725076
140780.8939World Health Organization priority antimicrobial resistance in Enterobacterales, Acinetobacter baumannii, Pseudomonas aeruginosa, Staphylococcus aureus and Enterococcus faecium healthcare-associated bloodstream infections in Brazil (ASCENSION): a prospective, multicentre, observational study. BACKGROUND: Carbapenem-resistant Enterobacterales (CRE), Acinetobacter baumannii (CRAB), Pseudomonas aeruginosa (CRPA), methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE) are listed by World Health Organization (WHO) as priority antimicrobial-resistant bacteria. Data on WHO Priority Antimicrobial resistance Phenotype (WPAP) bacteria from low- and middle-income countries are scarce. In this study, we investigated the occurrence of WPAP in healthcare-associated bloodstream infections (BSI) in Brazil, an upper-middle-income country in South America. METHODS: ASCENSION was a prospective, multicentre, observational study conducted in 14 hospitals from four of five Brazilian regions. Enterobacterales, A. baumannii, P. aeruginosa, S. aureus and E. faecium BSIs in hospitalised patients were analysed. The primary outcome was the frequency of WPAP among all bacteria of interest. Secondary outcomes were incidence-density of bacteria isolates in hospitalised patients, WPAP proportions within bacterial species, and 28-day mortality. PCR for carbapenemase genes was performed in carbapenem-resistant Gram-negative bacteria. FINDINGS: Between August 15, 2022, and August 14, 2023, 1350 isolates (1220 BSI episodes) were included. WPAP accounted for 38.8% (n = 524; 95% Confidence Interval 32.0-46.1) of all isolates, with CRE (19.3%) as the most frequent, followed by CRAB (9.6%), MRSA (4.9%), VRE (2.7%), and CRPA (2.4%). Incidence-density of all and WPAP isolates were 1.91 and 0.77/1000 patients-day, respectively. Carbapenem-resistant Klebsiella pneumoniae (CRKP) was the most common CRE, corresponding to 14.2% of all BSIs. A. baumannii isolates presented the highest proportion of WPAP (87.8%). Mortality rates were higher in patients with BSIs by WPAP than non-WPAP isolates. KPC (64.4%) was the predominant carbapenemase in CRE, followed by NDM (28.4%) and KPC + NDM co-production (7.1%). OXA-23 was the most frequent in CRAB. INTERPRETATION: A high frequency of WPAP bacteria, particularly CRKP and CRAB, were found in healthcare-associated BSIs in Brazil, posing them as a major public health problem in this country. FUNDING: National Council for Scientific and Technological Development, Brazil.202539957800
511990.8939ROCker models for reliable detection and typing of short-read sequences carrying mcr, erm, mph, and lnu antibiotic resistance genes. Quantitative monitoring of emerging antimicrobial resistance genes (ARGs) using short-read sequences remains challenging due to the high frequency of amino acid functional domains and motifs shared with related but functionally distinct (non-target) proteins. To facilitate ARG monitoring efforts using unassembled short reads, we present novel ROCker models for mcr, mph, erm, and lnu ARG families, as well as models for variants of special public health concern within these families, including mcr-1, mphA, ermB, lnuF, lnuB, and lnuG genes. For this, we curated target gene sequence sets for model training and built these models using the recently updated ROCker V2 pipeline (Gerhardt et al., in review). To validate our models, we simulated reads from the whole genome of ARG-carrying isolates spanning a range of common read lengths and used them to challenge the filtering efficacy of ROCker versus common static filtering approaches, such as similarity searches using BLASTx with various e-value thresholds or hidden Markov models. ROCker models consistently showed F1 scores up to 10× higher (31% higher on average) and lower false-positive (by 30%, on average) and false-negative (by 16%, on average) rates based on 250 bp reads compared to alternative methods. The ROCker models and all related reference materials and data are freely available through http://enve-omics.ce.gatech.edu/rocker/models, further expanding the available model collection previously developed for other genes. Their application to short-read metagenomes, metatranscriptomes, and PCR amplicon data should facilitate more accurate classification and quantification of unassembled short-read sequences for these ARG families and specific genes.IMPORTANCEAntimicrobial resistance gene families encoding erm and mph genes confer resistance to the macrolide class of antimicrobials, which are used to treat a wide range of infections. Similarly, the mcr gene family confers resistance to polymyxin E (colistin), a drug of last resort for many serious drug-resistant bacterial infections, and the lnu gene family confers resistance to lincomycin, which is reserved for patients allergic to penicillin or where bacteria have developed resistance to other antimicrobials. Assessing the prevalence of these genes in clinical or environmental samples and monitoring their spread to new pathogens are thus important for quantifying the associated public health risk. However, detecting these and other resistance genes in short-read sequence data is technically challenging. Our ROCker bioinformatic pipeline achieves reliable detection and typing of broad-range target gene sequences in complex data sets, thus contributing toward solving an important problem in ongoing surveillance efforts of antimicrobial resistance.202541143534
8439100.8939Comparative genomics analysis and virulence-related factors in novel Aliarcobacter faecis and Aliarcobacter lanthieri species identified as potential opportunistic pathogens. BACKGROUND: Emerging pathogenic bacteria are an increasing threat to public health. Two recently described species of the genus Aliarcobacter, A. faecis and A. lanthieri, isolated from human or livestock feces, are closely related to Aliarcobacter zoonotic pathogens (A. cryaerophilus, A. skirrowii, and A. butzleri). In this study, comparative genomics analysis was carried out to examine the virulence-related, including virulence, antibiotic, and toxin (VAT) factors in the reference strains of A. faecis and A. lanthieri that may enable them to become potentially opportunistic zoonotic pathogens. RESULTS: Our results showed that the genomes of the reference strains of both species have flagella genes (flaA, flaB, flgG, flhA, flhB, fliI, fliP, motA and cheY1) as motility and export apparatus, as well as genes encoding the Twin-arginine translocation (Tat) (tatA, tatB and tatC), type II (pulE and pulF) and III (fliF, fliN and ylqH) secretory pathways, allowing them to secrete proteins into the periplasm and host cells. Invasion and immune evasion genes (ciaB, iamA, mviN, pldA, irgA and fur2) are found in both species, while adherence genes (cadF and cj1349) are only found in A. lanthieri. Acid (clpB), heat (clpA and clpB), osmotic (mviN), and low-iron (irgA and fur2) stress resistance genes were observed in both species, although urease genes were not found in them. In addition, arcB, gyrA and gyrB were found in both species, mutations of which may mediate the resistance to quaternary ammonium compounds (QACs). Furthermore, 11 VAT genes including six virulence (cadF, ciaB, irgA, mviN, pldA, and tlyA), two antibiotic resistance [tet(O) and tet(W)] and three cytolethal distending toxin (cdtA, cdtB, and cdtC) genes were validated with the PCR assays. A. lanthieri tested positive for all 11 VAT genes. By contrast, A. faecis showed positive for ten genes except for cdtB because no PCR assay for this gene was available for this species. CONCLUSIONS: The identification of the virulence, antibiotic-resistance, and toxin genes in the genomes of A. faecis and A. lanthieri reference strains through comparative genomics analysis and PCR assays highlighted the potential zoonotic pathogenicity of these two species. However, it is necessary to extend this study to include more clinical and environmental strains to explore inter-species and strain-level genetic variations in virulence-related genes and assess their potential to be opportunistic pathogens for animals and humans.202235761183
5098110.8936Feature selection and aggregation for antibiotic resistance GWAS in Mycobacterium tuberculosis: a comparative study. INTRODUCTION: Drug resistance (DR) of pathogens remains a global healthcare concern. In contrast to other bacteria, acquiring mutations in the core genome is the main mechanism of drug resistance for Mycobacterium tuberculosis (MTB). For some antibiotics, the resistance of a particular isolate can be reliably predicted by identifying specific mutations, while for other antibiotics the knowledge of resistance mechanisms is limited. Statistical machine learning (ML) methods are used to infer new genes implicated in drug resistance leveraging large collections of isolates with known whole-genome sequences and phenotypic states for different drugs. However, high correlations between the phenotypic states for commonly used drugs complicate the inference of true associations of mutations with drug phenotypes by ML approaches. METHODS: Recently, several new methods have been developed to select a small subset of reliable predictors of the dependent variable, which may help reduce the number of spurious associations identified. In this study, we evaluated several such methods, namely, logistic regression with different regularization penalty functions, a recently introduced algorithm for solving the best-subset selection problem (ABESS) and "Hungry, Hungry SNPos" (HHS) a heuristic algorithm specifically developed to identify resistance-associated genetic variants in the presence of resistance co-occurrence. We assessed their ability to select known causal mutations for resistance to a specific drug while avoiding the selection of mutations in genes associated with resistance to other drugs, thus we compared selected ML models for their applicability for MTB genome wide association studies. RESULTS AND DISCUSSION: In our analysis, ABESS significantly outperformed the other methods, selecting more relevant sets of mutations. Additionally, we demonstrated that aggregating rare mutations within protein-coding genes into markers indicative of changes in PFAM domains improved prediction quality, and these markers were predominantly selected by ABESS, suggesting their high informativeness. However, ABESS yielded lower prediction accuracy compared to logistic regression methods with regularization.202540606161
6506120.8934Mitigating antimicrobial resistance through effective hospital wastewater management in low- and middle-income countries. Hospital wastewater (HWW) is a significant environmental and public health threat, containing high levels of pollutants such as antibiotic-resistant bacteria (ARB), antibiotic-resistant genes (ARGs), antibiotics, disinfectants, and heavy metals. This threat is of particular concern in low- and middle-income countries (LMICs), where untreated effluents are often used for irrigating vegetables crops, leading to direct and indirect human exposure. Despite being a potential hotspot for the spread of antimicrobial resistance (AMR), existing HWW treatment systems in LMICs primarily target conventional pollutants and lack effective standards for monitoring the removal of ARB and ARGs. Consequently, untreated or inadequately treated HWW continues to disseminate ARB and ARGs, exacerbating the risk of AMR proliferation. Addressing this requires targeted interventions, including cost-effective treatment solutions, robust AMR monitoring protocols, and policy-driven strategies tailored to LMICs. This perspective calls for a paradigm shift in HWW management in LMIC, emphasizing the broader implementation of onsite treatment systems, which are currently rare. Key recommendations include developing affordable and contextually adaptable technologies for eliminating ARB and ARGs and enforcing local regulations for AMR monitoring and control in wastewater. Addressing these challenges is essential for protecting public health, preventing the environmental spread of resistance, and contributing to a global effort to preserve the efficacy of antibiotics. Recommendations include integrating scalable onsite technologies, leveraging local knowledge, and implementing comprehensive AMR-focused regulatory frameworks.202439944563
6577130.8934Evaluating Microbial and Chemical Hazards in Commercial Struvite Recovered from Wastewater. Controlled struvite (NH(4)MgPO(4)·6H(2)O) precipitation has become a well-known process for nutrient recovery from wastewater treatment systems to alleviate the pressures of diminishing, finite rock phosphate reservoirs. Nonetheless, coprecipitation of potential microbial and chemical hazards is poorly understood. On the other hand, antimicrobial resistance (AMR) is a major global public health concern and wastewater is thought to disseminate resistance genes within bacteria. Fecal indicator bacteria (FIB) are typically used as measures of treatment quality, and with multiresistant E. coli and Enterococcus spp. rising in concern, the quantification of FIB can be used as a preliminary method to assess the risk of AMR. Focusing on struvite produced from full-scale operations, culture and qPCR methods were utilized to identify FIB, antibiotic resistance genes, and human enteric viruses in the final product. Detection of these hazards occurred in both wet and dry struvite samples indicating that there is a potential risk that needs further consideration. Chemical and biological analyses support the idea that the presence of other wastewater components can impact struvite formation through ion and microbial interference. While heavy metal concentrations met current fertilizer standards, the presence of K, Na, Ca, and Fe ions can impact struvite purity yet provide benefit for agricultural uses. Additionally, the quantified hazards detected varied among struvite samples produced from different methods and sources, thus indicating that production methods could be a large factor in the risk associated with wastewater-recovered struvite. In all, coprecipitation of metals, fecal indicator bacteria, antimicrobial resistance genes, and human enteric viruses with struvite was shown to be likely, and future engineered wastewater systems producing struvite may require additional step(s) to manage these newly identified public health risks.201930964655
2525140.8930Review of antimicrobial resistance surveillance programmes in livestock and meat in EU with focus on humans. OBJECTIVES: In this review, we describe surveillance programmes reporting antimicrobial resistance (AMR) and resistance genes in bacterial isolates from livestock and meat and compare them with those relevant for human health. METHODS: Publications on AMR in European countries were assessed. PubMed was reviewed and AMR monitoring programmes were identified from reports retrieved by Internet searches and by contacting national authorities in EU/European Economic Area (EEA) member states. RESULTS: Three types of systems were identified: EU programmes, industry-funded supranational programmes and national surveillance systems. The mandatory EU-financed programme has led to some harmonization in national monitoring and provides relevant information on AMR and extended-spectrum β-lactamase/AmpC- and carbapenemase-producing bacteria. At the national level, AMR surveillance systems in livestock apply heterogeneous sampling, testing and reporting modalities, resulting in results that cannot be compared. Most reports are not publicly available or are written in a local language. The industry-funded monitoring systems undertaken by the Centre Européen d'Etudes pour la Santé Animale (CEESA) examines AMR in bacteria in food-producing animals. CONCLUSIONS: Characterization of AMR genes in livestock is applied heterogeneously among countries. Most antibiotics of human interest are included in animal surveillance, although results are difficult to compare as a result of lack of representativeness of animal samples. We suggest that EU/EEA countries provide better uniform AMR monitoring and reporting in livestock and link them better to surveillance systems in humans. Reducing the delay between data collection and publication is also important to allow prompt identification of new resistance patterns.201828970159
6690150.8930Antimicrobial resistance situation in animal health of Bangladesh. Antimicrobial resistance (AMR) is a crucial multifactorial and complex global problem and Bangladesh poses a regional and global threat with a high degree of antibiotic resistance. Although the routine application of antimicrobials in the livestock industry has largely contributed to the health and productivity, it correspondingly plays a significant role in the evolution of different pathogenic bacterial strains having multidrug resistance (MDR) properties. Bangladesh is implementing the National Action Plan (NAP) for containing AMR in human, animal, and environment sectors through "One Health" approach where the Department of Livestock Services (DLS) is the mandated body to implement NAP strategies in the animal health sector of the country. This review presents a "snapshot" of the predisposing factors, and current situations of AMR along with the weakness and strength of DLS to contain the problem in animal farming practices in Bangladesh. In the present review, resistance monitoring data and risk assessment identified several direct and/or indirect predisposing factors to be potentially associated with AMR development in the animal health sector of Bangladesh. The predisposing factors are inadequate veterinary healthcare, monitoring and regulatory services, intervention of excessive informal animal health service providers, and farmers' knowledge gap on drugs, and AMR which have resulted in the misuse and overuse of antibiotics, ultimate in the evolution of antibiotic-resistant bacteria and genes in all types of animal farming settings of Bangladesh. MDR bacteria with extreme resistance against antibiotics recommended to use in both animals and humans have been reported and been being a potential public health hazard in Bangladesh. Execution of extensive AMR surveillance in veterinary practices and awareness-building programs for stakeholders along with the strengthening of the capacity of DLS are recommended for effective containment of AMR emergence and dissemination in the animal health sector of Bangladesh.202033487990
2260160.8930Current status of resistance to antibiotics in the Democratic Republic of the Congo: A review. A review of literature was conducted to assess the prevalence and mechanisms of antibiotic resistance to date, mainly to β-lactam antibiotics, cephalosporins, carbapenems, colistin, and tigecycline in the Democratic Republic of the Congo (DRC). English and French publications were listed and analysed using PubMed/Medline, Google Scholar, and African Journals database between 1 January 1990 and 31 December 2019. For the 30 published articles found: (1) bacterial resistance to antibiotics concerned both Gram-negative and Gram-positive bacteria; (2) multidrug resistance prevalence was the same in half of Streptococcus pneumoniae isolates; (3) a worrying prevalence of methicillin-resistant Staphylococcus aureus (MRSA) was noted, which is associated with co-resistance to several other antibiotics; and (4) resistance to third-generation cephalosporins was very high in Enterobacteriaceae, mainly because of bla(CTX-M-1) group and bla(SHV) genes. Data on carbapenem and colistin resistance were not available in DRC until recently. Further work is required to set up a surveillance system for antibiotic resistance in DRC.202032688007
6691170.8929The antimicrobial resistance monitoring and research (ARMoR) program: the US Department of Defense response to escalating antimicrobial resistance. Responding to escalating antimicrobial resistance (AMR), the US Department of Defense implemented an enterprise-wide collaboration, the Antimicrobial Resistance Monitoring and Research Program, to aid in infection prevention and control. It consists of a network of epidemiologists, bioinformaticists, microbiology researchers, policy makers, hospital-based infection preventionists, and healthcare providers who collaborate to collect relevant AMR data, conduct centralized molecular characterization, and use AMR characterization feedback to implement appropriate infection prevention and control measures and influence policy. A particularly concerning type of AMR, carbapenem-resistant Enterobacteriaceae, significantly declined after the program was launched. Similarly, there have been no further reports or outbreaks of another concerning type of AMR, colistin resistance in Acinetobacter, in the Department of Defense since the program was initiated. However, bacteria containing AMR-encoding genes are increasing. To update program stakeholders and other healthcare systems facing such challenges, we describe the processes and impact of the program.201424795331
9068180.8928TnCentral: a Prokaryotic Transposable Element Database and Web Portal for Transposon Analysis. We describe here the structure and organization of TnCentral (https://tncentral.proteininformationresource.org/ [or the mirror link at https://tncentral.ncc.unesp.br/]), a web resource for prokaryotic transposable elements (TE). TnCentral currently contains ∼400 carefully annotated TE, including transposons from the Tn3, Tn7, Tn402, and Tn554 families; compound transposons; integrons; and associated insertion sequences (IS). These TE carry passenger genes, including genes conferring resistance to over 25 classes of antibiotics and nine types of heavy metal, as well as genes responsible for pathogenesis in plants, toxin/antitoxin gene pairs, transcription factors, and genes involved in metabolism. Each TE has its own entry page, providing details about its transposition genes, passenger genes, and other sequence features required for transposition, as well as a graphical map of all features. TnCentral content can be browsed and queried through text- and sequence-based searches with a graphic output. We describe three use cases, which illustrate how the search interface, results tables, and entry pages can be used to explore and compare TE. TnCentral also includes downloadable software to facilitate user-driven identification, with manual annotation, of certain types of TE in genomic sequences. Through the TnCentral homepage, users can also access TnPedia, which provides comprehensive reviews of the major TE families, including an extensive general section and specialized sections with descriptions of insertion sequence and transposon families. TnCentral and TnPedia are intuitive resources that can be used by clinicians and scientists to assess TE diversity in clinical, veterinary, and environmental samples. IMPORTANCE The ability of bacteria to undergo rapid evolution and adapt to changing environmental circumstances drives the public health crisis of multiple antibiotic resistance, as well as outbreaks of disease in economically important agricultural crops and animal husbandry. Prokaryotic transposable elements (TE) play a critical role in this. Many carry "passenger genes" (not required for the transposition process) conferring resistance to antibiotics or heavy metals or causing disease in plants and animals. Passenger genes are spread by normal TE transposition activities and by insertion into plasmids, which then spread via conjugation within and across bacterial populations. Thus, an understanding of TE composition and transposition mechanisms is key to developing strategies to combat bacterial pathogenesis. Toward this end, we have developed TnCentral, a bioinformatics resource dedicated to describing and exploring the structural and functional features of prokaryotic TE whose use is intuitive and accessible to users with or without bioinformatics expertise.202134517763
4999190.8928Dissemination Routes of Carbapenem and Pan-Aminoglycoside Resistance Mechanisms in Hospital and Urban Wastewater Canalizations of Ghana. Wastewater has a major role in antimicrobial resistance (AMR) dynamics and public health. The impact on AMR of wastewater flux at the community-hospital interface in low- and middle-income countries (LMICs) is poorly understood. Therefore, the present study analyzed the epidemiological scenario of resistance genes, mobile genetic elements (MGEs), and bacterial populations in wastewater around the Tamale metropolitan area (Ghana). Wastewater samples were collected from the drainage and canalizations before and after three hospitals and one urban waste treatment plant (UWTP). From all carbapenem/pan-aminoglycoside-resistant bacteria, 36 isolates were selected to determine bacterial species and phenotypical resistance profiles. Nanopore sequencing was used to screen resistance genes and plasmids, whereas, sequence types, resistome and plasmidome contents, pan-genome structures, and resistance gene variants were analyzed with Illumina sequencing. The combination of these sequencing data allowed for the resolution of the resistance gene-carrying platforms. Hospitals and the UWTP collected genetic and bacterial elements from community wastewater and amplified successful resistance gene-bacterium associations, which reached the community canalizations. Uncommon carbapenemase/β-lactamase gene variants, like bla(DIM-1), and novel variants, including bla(VIM-71), bla(CARB-53), and bla(CMY-172), were identified and seem to spread via clonal expansion of environmental Pseudomonas spp. However, bla(NDM-1), bla(CTX-M-15), and armA genes, among others, were associated with MGEs that allowed for their dissemination between environmental and clinical bacterial hosts. In conclusion, untreated hospital wastewater in Ghana is a hot spot for the emergence and spread of genes and gene-plasmid-bacterium associations that accelerate AMR, including to last-resort antibiotics. Urgent actions must be taken in wastewater management in LMICs in order to delay AMR expansion. IMPORTANCE Antimicrobial resistance (AMR) is one the major threats to public health today, especially resistance to last-resort compounds for the treatment of critical infections, such as carbapenems and aminoglycosides. Innumerable works have focused on the clinical ambit of AMR, but studies addressing the impact of wastewater cycles on the emergence and dissemination of resistant bacteria are still limited. The lack of knowledge is even greater when referring to low- and middle-income countries, where there is an absence of accurate sanitary systems. Furthermore, the combination of short- and long-read sequencing has surpassed former technical limitations, allowing the complete characterization of resistance genes, mobile genetic platforms, plasmids, and bacteria. The present study deciphered the multiple elements and routes involved in AMR dynamics in wastewater canalizations and, therefore, in the local population of Tamale, providing the basis to adopt accurate control measures to preserve and promote public health.202235103490