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International Journal of Environmental... Jun 2024Antibiotic resistance, a significant public health hazard, is predicted to cause 10 million deaths worldwide by 2050. The study aimed to identify culturable bioaerosols...
Antibiotic resistance, a significant public health hazard, is predicted to cause 10 million deaths worldwide by 2050. The study aimed to identify culturable bioaerosols in the indoor air of dental units in Lahore and assess their antibiotic resistance. Air samples were collected from 10 dental unit locations at different distances, with average concentrations of fungi and bacteria falling within intermediate ranges, per the Global Index of Microbial Contamination (GIMC/m3) index. The study found higher antibiotic-resistant strains in hospital dental units, particularly during winter. The most vigorous strain, -NAJIH18, exhibited 70% resistance to ceftazidime. The research highlights the importance of quantifying microbial pollutants for evaluating their source and complexity. It suggests proactive mitigation techniques, such as focused cleaning and air filtration, to improve indoor air quality can mitigate the spread of antibiotic-resistant strains. These insights offer hope in combating the growing public health threat of antibiotic resistance.
PubMed: 38944751
DOI: 10.1080/09603123.2024.2373173 -
Nature Communications Jun 2024Real-time genomics through nanopore sequencing holds the promise of fast antibiotic resistance prediction directly in the clinical setting. However, concerns about the...
Real-time genomics through nanopore sequencing holds the promise of fast antibiotic resistance prediction directly in the clinical setting. However, concerns about the accuracy of genomics-based resistance predictions persist, particularly when compared to traditional, clinically established diagnostic methods. Here, we leverage the case of a multi-drug resistant Klebsiella pneumoniae infection to demonstrate how real-time genomics can enhance the accuracy of antibiotic resistance profiling in complex infection scenarios. Our results show that unlike established diagnostics, nanopore sequencing data analysis can accurately detect low-abundance plasmid-mediated resistance, which often remains undetected by conventional methods. This capability has direct implications for clinical practice, where such "hidden" resistance profiles can critically influence treatment decisions. Consequently, the rapid, in situ application of real-time genomics holds significant promise for improving clinical decision-making and patient outcomes.
Topics: Klebsiella pneumoniae; Genomics; Humans; Anti-Bacterial Agents; Klebsiella Infections; Drug Resistance, Multiple, Bacterial; Plasmids; Nanopore Sequencing; Genome, Bacterial; Microbial Sensitivity Tests
PubMed: 38944650
DOI: 10.1038/s41467-024-49851-4 -
Chemosphere Jun 2024Adding heavy metals such as copper and zinc to animal feeds is common practice to promote growth, but meanwhile has side consequence of enhancing spread of antibiotic...
Adding heavy metals such as copper and zinc to animal feeds is common practice to promote growth, but meanwhile has side consequence of enhancing spread of antibiotic resistance genes (ARGs) in soil. This presents a global challenge to food security and human health. We in this study investigated the transmission of typical ARGs, i. e. β-lactamase genes (β-RGs), in dairy farm environments where dietary Cu and Zn were present in a wide range of concentration. The β-RGs were demonstrated to be highly prevalent across environmental media, with a relative abundance of 94.55%, dominated by mechanisms of antibiotic deactivation (93.75%) and cellular protection (6.25%). More importantly, we first found the transmission of ARGs to be highly dependent on the overlooked volcanic effect, i. e. low-concentration Cu (12-22 mg/kg) and Zn (45-80 mg/kg) acted as micronutrients necessary for microbial growth but facilitated ARGs transfer, whereas higher-concentration Cu (22-39 mg/kg) and Zn (80-153 mg/kg) became toxic to microbial communities and gene expression patterns. Notably, the specific microbial phyla Proteobacteria (2.28-82.94%), Bacteroidetes (0.02-56.48%) and Actinobacteria (1.62-12.92%) exhibited resistance at low concentration of Cu and Zn, which enhanced the transmission of β-RGs. However, this process was inhibited at higher concentration due to inactivation of microbes by Cu and Zn. The increase in resistance was first observed in class Gammaproteobacteria (2.02-88.51%) and Alphaproteobacteria (0.68-10.1%) with increased Cu and Zn concentration. This resulted in heightened transfer of ARGs by tnpA-07 (80.35%) due to protection of thicker cell membrane by chelation with Cu and Zn. This study not only offers mechanistic insights into the volcanic effect of dietary metals on dissemination of ARGs, but also has important implications for safe management of agricultural settings.
PubMed: 38944351
DOI: 10.1016/j.chemosphere.2024.142713 -
Biochimie Jun 2024Antibiotic resistance has become one of the most serious threats to human health in recent years. In response to the increasing microbial resistance to the antibiotics... (Review)
Review
Antibiotic resistance has become one of the most serious threats to human health in recent years. In response to the increasing microbial resistance to the antibiotics currently available, it is imperative to develop new antibiotics or explore new approaches to combat antibiotic resistance. Antimicrobial peptides (AMPs) have shown considerable promise in this regard, as the microbes develop low or no resistance against them. The discovery and development of AMPs still confront numerous obstacles such as finding a target, developing assays, and identifying hits and leads, which are time-consuming processes, making it difficult to reach the market. However, with the advent of genome mining, new antibiotics could be discovered efficiently using tools such as BAGEL, antiSMASH, RODEO, etc., providing hope for better treatment of diseases in the future. Computational methods used in genome mining automatically detect and annotate biosynthetic gene clusters in genomic data, making it a useful tool in natural product discovery. This review aims to shed light on the history, diversity, and mechanisms of action of AMPs and the data on new AMPs identified by traditional as well as genome mining strategies. It further substantiates the various phases of clinical trials for some AMPs, as well as an overview of genome mining databases and tools built expressly for AMP discovery. In light of the recent advancements, it is evident that targeted genome mining stands as a beacon of hope, offering immense potential to expedite the discovery of novel antimicrobials.
PubMed: 38944107
DOI: 10.1016/j.biochi.2024.06.013 -
Environmental Research Jun 2024Antibiotic resistance gene contamination in polluted rivers remains a widely acknowledged environmental issue. This study focused on investigating the contamination...
Antibiotic resistance gene contamination in polluted rivers remains a widely acknowledged environmental issue. This study focused on investigating the contamination conditions of antibiotic resistance genes (ARGs) in Harbin's urban black-odor rivers, specifically Dongfeng Ditch and Hejia Ditch. The research employed a SmartChip Real-Time PCR System to explore the types, abundance, and distribution of ARGs in diverse habitats, such as surface water and sediment. Additionally, the study examined the correlation of ARGs with mobile genetic elements (MGEs) and various environmental factors. It was found that antibiotic resistance genes were prevalent in both water and sediment within the black-odor ditches. The dominant types of ARGs identified included aminoglycoside, sulfonamide, multidrug-resistant, and β-lactam ARGs. Notably, the top four ARGs, in terms of relative abundance, were sul1, fox5, qacEdelta1-01 and aadA1. Most categories of ARGs have significant positive connections with MGEs, indicating that the enrichment and spreading of ARGs in rivers are closely related to MGEs. Based on the correlation analysis, it is found that environmental factors such as dissolved oxygen (DO), ammonia nitrogen (NH-N), and phosphate (PO-P) played a substantial role in influencing the variations observed in ARGs. By employing a risk assessment framework based on the human association, host pathogenicity, and mobility of ARGs, the identification of seven high-risk ARGs was achieved. In addition, it is important to assess the environmental risk of ARGs from multiple perspectives (abundance、detection rate、mobility).This study provides a significant reference regarding the presence of ARGs contamination in urban inland black-odor rivers, essential for assessing the health risks associated with ARGs and devising strategies to mitigate the threat of antibiotic resistance.
PubMed: 38944102
DOI: 10.1016/j.envres.2024.119497 -
Epidemics Jun 2024Antibiotic-resistant Enterobacterales (ARE) are a public health threat worldwide. Dissemination of these opportunistic pathogens has been largely studied in hospitals....
BACKGROUND
Antibiotic-resistant Enterobacterales (ARE) are a public health threat worldwide. Dissemination of these opportunistic pathogens has been largely studied in hospitals. Despite high prevalence of asymptomatic colonization in the community in some regions of the world, less is known about ARE acquisition and spread in this setting. As explaining the community ARE dynamics has not been straightforward, mathematical models can be key to explore underlying phenomena and further evaluate the impact of interventions to curb ARE circulation outside of hospitals.
METHODS
We conducted a systematic review of mathematical modeling studies focusing on the transmission of AR-E in the community, excluding models only specific to hospitals. We extracted model features (population, setting), formalism (compartmental, individual-based), biological hypotheses (transmission, infection, antibiotic impact, resistant strain specificities) and main findings. We discussed additional mechanisms to be considered, open scientific questions, and most pressing data needs.
RESULTS
We identified 18 modeling studies focusing on the human transmission of ARE in the community (n=11) or in both community and hospital (n=7). Models aimed at (i) understanding mechanisms driving resistance dynamics; (ii) identifying and quantifying transmission routes; or (iii) evaluating public health interventions to reduce resistance. To overcome the difficulty of reproducing observed ARE dynamics in the community using the classical two-strains competition model, studies proposed to include mechanisms such as within-host strain competition or a strong host population structure. Studies inferring model parameters from longitudinal carriage data were mostly based on models considering the ARE strain only. They showed differences in ARE carriage duration depending on the acquisition mode: returning travelers have a significantly shorter carriage duration than discharged hospitalized patient or healthy individuals. Interestingly, predictions across models regarding the success of public health interventions to reduce ARE rates depended on pathogens, settings, and antibiotic resistance mechanisms. For E. coli, reducing person-to-person transmission in the community had a stronger effect than reducing antibiotic use in the community. For Klebsiella pneumoniae, reducing antibiotic use in hospitals was more efficient than reducing community use.
CONCLUSIONS
This study raises the limited number of modeling studies specifically addressing the transmission of ARE in the community. It highlights the need for model development and community-based data collection especially in low- and middle-income countries to better understand acquisition routes and their relative contribution to observed ARE levels. Such modeling will be critical to correctly design and evaluate public health interventions to control ARE transmission in the community and further reduce the associated infection burden.
PubMed: 38944024
DOI: 10.1016/j.epidem.2024.100783 -
Water Research Jun 2024High-strength nitrogen and antibiotics-containing wastewater can be efficiently eliminated by simultaneous denitrification and methanogenesis (SDM). Heavy metals and...
Fate of antibiotic resistance genes and EPS defence mechanisms during simultaneous denitrification and methanogenesis, coupled with the biodegradation of multiple antibiotics under zinc stress.
High-strength nitrogen and antibiotics-containing wastewater can be efficiently eliminated by simultaneous denitrification and methanogenesis (SDM). Heavy metals and antibiotics are two critical factors that can lead to horizontal transfer of antibiotic resistance genes (ARGs), which can be simultaneously detected in wastewater. Unfortunately, the impacts of heavy metals on SDM and antibiotic biodegradation have not been fully elucidated. Herein, the effects of SDM and multiple antibiotics biodegradation, extracellular polymeric substances (EPSs) and protein response mechanisms, and ARG fate under Zn(II) stress were comprehensively evaluated. The results indicated that a high level of Zn(II) (≥5 mg/L) stress significantly decreased the degradation rate of multiple antibiotics and suppressed denitrification and methanogenesis. In addition, Zn(II) exposure prompted the liberation of proteins from microbes into the EPSs, and the combination of EPSs with small molecules quenched the original fluorescent components and destroyed the protein structure. The dominant proteins can bind to both Zn(II) and multiple antibiotics through several types of chemical interactions, including metallic and hydrogen bonds, hydrophobic interactions, and salt bridges, relieving the toxicity of harmful substances. Moreover, metagenomic sequencing revealed that the abundance of zinc resistance genes (Zn-RGs), ARGs (mainly tetracyclines), and mobile genetic elements (MGEs) increased under Zn(II) stress. Mantel test illustrated that the ARGs mecD, tetT, and tetB(60) were most affected by MGEs. Moreover, molecular network analysis revealed that several MGEs can bridge metal resistance genes (MRGs) and ARGs, facilitating the horizontal transfer of ARGs. This study provides theoretical guidance for the environmental risk control of antibiotics-containing wastewater treated by an SDM system.
PubMed: 38943999
DOI: 10.1016/j.watres.2024.121996 -
Environment International Jun 2024Antimicrobial resistance (AMR) stands as an escalating public health crisis fueled by antimicrobial residues in the environment, particularly in soil, which acts as a...
Antimicrobial resistance (AMR) stands as an escalating public health crisis fueled by antimicrobial residues in the environment, particularly in soil, which acts as a reservoir for antimicrobial resistance genes (ARGs). Merely quantifying the total extractable concentration of antimicrobials, instead of bioavailable fractions, may substantially underestimate their minimal selection concentration for propagating ARGs. To shed light on the role of bioavailability in ARG abundance within soil, a systematic bioavailability assessment method was established for accurately quantifying the partitioning of multi-class antimicrobials in representative Chinese soils. Microcosm studies unveiled that antimicrobials persisting in the bioavailable fraction could potentially prolong their selection pressure duration to trigger AMR. Notably, the co-occurrence of pesticide or steroid hormone influenced the development trends of ARG subtypes, with fluoroquinolone resistance genes (RGs) being particularly susceptible. Partial least squares path model (PLS-PM) analysis uncovered potentially distinct induction mechanisms of antimicrobials: observable results suggested that extractable residual concentration may exert a direct selection pressure on the development of ARGs, while bioavailable concentration could potentially play a stepwise role in affecting the abundance of mobile genetic elements and initiating ARG dissemination. Such unprecedented scrutinization of the interplay between bioavailable antimicrobials in soils and ARG abundance provides valuable insights into strategizing regulatory policy or guidelines for soil remediation.
PubMed: 38943926
DOI: 10.1016/j.envint.2024.108830 -
Molekuliarnaia Biologiia 2024Production of extracellular membrane vesicles plays an important role in communication in bacterial populations and in bacteria-host interactions. Vesicles as carriers...
Production of extracellular membrane vesicles plays an important role in communication in bacterial populations and in bacteria-host interactions. Vesicles as carriers of various regulatory and signaling molecules may be potentially used as disease biomarkers and promising therapeutic agents, including vaccine preparations. The composition of membrane vesicles has been deciphered for a limited number of Gram-negative and Gram-positive bacteria. In this work, for the first time, extracellular membrane vesicles of a streptomycin-resistant strain Bacillus pumilus 3-19, a producer of extracellular guanyl-preferring ribonuclease binase, are isolated, visualized, and characterized by their genome and proteome composition. It has been established that there is no genetic material in the vesicles and the spectrum of the proteins differs depending on the phosphate content in the culture medium of the strain. Vesicles from a phosphate-deficient medium carry 49 unique proteins in comparison with 101 from a medium with the high phosphate content. The two types of vesicles had 140 mutual proteins. Flagellar proteins, RNase J, which is the main enzyme of RNA degradosomes, phosphatases, peptidases, iron transporters, signal peptides, were identified in vesicles. Antibiotic resistance proteins and amyloid-like proteins whose genes are present in B. pumilus 3-19 cells are absent. Phosphate deficiency-induced binase was found only in vesicles from a phosphate-deficient medium.
Topics: Bacillus pumilus; Extracellular Vesicles; Proteome; Bacterial Proteins; Ribonucleases; Phosphates; Drug Resistance, Bacterial; Endoribonucleases
PubMed: 38943590
DOI: No ID Found -
Critical Care (London, England) Jun 2024Gut colonization with multidrug-resistant organisms (MDRO) frequently precedes infection among patients in the intensive care unit (ICU), although the dynamics of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Gut colonization with multidrug-resistant organisms (MDRO) frequently precedes infection among patients in the intensive care unit (ICU), although the dynamics of colonization are not completely understood. We performed a systematic review and meta-analysis of ICU studies which described the cumulative incidence and rates of MDRO gut acquisition.
METHODS
We systematically searched PubMed, Embase, and Web of Science for studies published from 2010 to 2023 reporting on gut acquisition of MDRO in the ICU. MDRO were defined as multidrug resistant non-Pseudomonas Gram-negative bacteria (NP-GN), Pseudomonas spp., and vancomycin-resistant Enterococcus (VRE). We included observational studies which obtained perianal or rectal swabs at ICU admission (within 48 h) and at one or more subsequent timepoints. Our primary outcome was the incidence rate of gut acquisition of MDRO, defined as any MDRO newly detected after ICU admission (i.e., not present at baseline) for all patient-time at risk. The study was registered with PROSPERO, CRD42023481569.
RESULTS
Of 482 studies initially identified, 14 studies with 37,305 patients met criteria for inclusion. The pooled incidence of gut acquisition of MDRO during ICU hospitalization was 5% (range: 1-43%) with a pooled incidence rate of 12.2 (95% CI 8.1-18.6) per 1000 patient-days. Median time to acquisition ranged from 4 to 26 days after ICU admission. Results were similar for NP-GN and Pseudomonas spp., with insufficient data to assess VRE. Among six studies which provided sufficient data to perform curve fitting, there was a quasi-linear increase in gut MDRO colonization of 1.41% per day which was stable through 30 days of ICU hospitalization (R = 0.50, p < 0.01).
CONCLUSIONS
Acquisition of gut MDRO was common in the ICU and increases with days spent in ICU through 30 days of follow-up. These data may guide future interventions seeking to prevent gut acquisition of MDRO in the ICU.
Topics: Humans; Intensive Care Units; Drug Resistance, Multiple, Bacterial; Vancomycin-Resistant Enterococci; Incidence
PubMed: 38943133
DOI: 10.1186/s13054-024-04999-9