Front Oncol. 2024 Oct 18;14:1449636. doi: 10.3389/fonc.2024.1449636. eCollection 2024.

NO ABSTRACT

PMID:39493454 | PMC:PMC11527702 | DOI:10.3389/fonc.2024.1449636

Dis Model Mech. 2024 Nov 4:dmm.050716. doi: 10.1242/dmm.050716. Online ahead of print.

ABSTRACT

The tumour microenvironment (TME) significantly influences tumour formation and progression through dynamic interactions. Cholangiocarcinoma (CCA), a highly desmoplastic tumour, lacks early diagnostic biomarkers and has limited effective treatments due to an incomplete understanding of its molecular pathogenesis. Investigating the TME's role in CCA progression could lead to better therapies. RNA sequencing was performed on seven CCA PDXs and their corresponding patient samples. Differential expression analysis was conducted, and Qiagen Ingenuity Pathway Analysis (IPA) was used to predict dysregulated pathways and upstream regulators. PDX and cell line-derived spheroids, with and without immortalised mesenchymal stem cells, were grown and analysed for morphology, growth, and viability. Histological analysis confirmed biliary phenotypes. RNA sequencing indicated upregulation of ECM-receptor interaction and PI3K-Akt pathways in the presence of MSCs, with several genes linked to poor survival. MSCs restored the activity of inhibited cancer-associated kinases (ICAKs). This study shows that adding MSCs to CCA spheroid models restores key paracrine signalling pathways lost in PDXs, enhancing tumour growth and viability. These findings highlight the importance of including stromal components in cancer models to improve pre-clinical studies.

PMID:39492622 | DOI:10.1242/dmm.050716

Biosystems. 2023 Oct 28:105067. doi: 10.1016/j.biosystems.2023.105067. Online ahead of print.

ABSTRACT

Since its conception some fifty years ago, metabolic control analysis (MCA) aims to understand how cells control their metabolism by adjusting the activity of their enzymes. Here we extend its scope to a whole-cell context. We consider metabolism in the evolutionary context of growth-rate maximisation by optimisation of protein concentrations. This framework allows for the prediction of flux control coefficients from proteomics data or stoichiometric modelling. Since genes compete for finite biosynthetic resources, we treat all protein concentrations as interdependent. We show that elementary flux modes (EFMs) emerge naturally as the optimal metabolic networks in the whole-cell context and we derive their control properties. In the evolutionary optimum, the number of expressed EFMs is determined by the number of protein-concentration constraints that limit growth rate. We use published glucose-limited chemostat data of S. cerevisiae to illustrate that it uses only two EFMs prior to the onset of fermentation and that it uses four EFMs during fermentation. We discuss published enzyme-titration data to show that S. cerevisiae and E. coli indeed can express proteins at growth-rate maximising concentrations. Accordingly, we extend MCA to elementary flux modes operating at an optimal state. We find that the expression of growth-unassociated proteins changes results from classical metabolic control analysis. Finally, we show how flux control coefficients can be estimated from proteomics and ribosome-profiling data. We analyse published proteomics data of E. coli to provide a whole-cell perspective of the control of metabolic enzymes on growth rate. We hope that this paper stimulates a renewed interest in metabolic control analysis, so that it can serve again the purpose it once had: to identify general principles that emerge from the biochemistry of the cell and are conserved across biological species.

PMID:39492480 | DOI:10.1016/j.biosystems.2023.105067

Biomed Pharmacother. 2023 Oct 28;168:115793. doi: 10.1016/j.biopha.2023.115793. Online ahead of print.

ABSTRACT

Given the rise of multidrug-resistant (MDR) Pseudomonas aeruginosa infections, alternative treatments are needed. Anti-pseudomonal phage therapy shows promise, but its clinical application is limited due to the development of resistance and a lack of biofilm penetration. Recently, adjuvants like CaEDTA have shown the ability to enhance the effectiveness of combined antimicrobial agents. Here, we tested a phage-adjuvant combination and demonstrated the effectiveness of intranasally inhaled phage (KKP10) + CaEDTA in addition to ceftazidime/avibactam (CZA) for chronic P. aeruginosa lung infections. The results emphasize that intranasal inhalation of phage along with CaEDTA can successfully re-sensitize MDR P. aeruginosa to CZA in a triple combination treatment. This promising approach shows potential as a therapy for chronic respiratory tract infections.

PMID:39491417 | DOI:10.1016/j.biopha.2023.115793

Am J Transplant. 2023 Oct 27:S1600-6135(23)00818-3. doi: 10.1016/j.ajt.2023.10.016. Online ahead of print.

ABSTRACT

The XVI-th Banff Meeting for Allograft Pathology was held in Banff, Alberta, Canada, from 19th-23rd September 2022, as a joint meeting with the Canadian Society of Transplantation. To mark the 30th anniversary of the first Banff Classification, pre-meeting discussions were held on the past, present, and future of the Banff Classification. This report is a summary of the meeting highlights that were most important in terms of their effect on the Classification, including discussions around microvascular inflammation and biopsy-based transcript analysis for diagnosis. In a post-meeting survey, agreement was reached on the delineation of the following phenotypes: (1) "Probable antibody-mediated rejection (AMR)", which represents DSA-positive cases with some histological features of AMR but below current thresholds for a definitive AMR diagnosis; and (2) "Microvascular inflammation (MVI), DSA-negative and C4d-negative", a phenotype of unclear cause requiring further study, which represents cases with MVI not explained by DSA. Although biopsy-based transcript diagnostics are considered promising and remain an integral part of the Banff Classification (limited to diagnosis of AMR), further work needs to be done to agree on the exact classifiers, thresholds, and clinical context of use.

PMID:39491095 | DOI:10.1016/j.ajt.2023.10.016

J Lipid Res. 2024 Oct 25:100678. doi: 10.1016/j.jlr.2024.100678. Online ahead of print.

ABSTRACT

Plasma high-density lipoprotein (HDL), originally studied for its role in lipid transport, is now appreciated to have wide-ranging biological functions that become defective during disease. While >200 lipids have collectively been detected in HDL, published HDL lipidomic analyses in different diseases have commonly been targeted to prespecified subsets of lipids. Here, we report the results of untargeted lipidomic analysis of HDL isolated from 101 subjects referred for computed tomographic coronary imaging for whom multiple additional clinical and lipoprotein metadata were measured. Unsupervised clustering of the total HDL lipidome revealed that the subjects fell into one of two discrete groups, herein referred to as HDL 'metabotypes'. Subjects in metabotype 1 were likelier to be female and tended to have a less atherogenic lipoprotein profile, higher HDL cholesterol efflux capacity (CEC), and lower-grade non-calcified burden on coronary imaging than metabotype 2 counterparts. Specific lipids were relatively enriched in metabotype 1 HDL. Linear modeling revealed that several of these lipids were positively associated with CEC, statin use, HDL size, and HDL particle number, and positively correlated with HDL apolipoprotein A-1, suggesting that they may be informative HDL biomarkers. Taken together, we posit a novel, clinically relevant categorization for HDL revealed by systems biology.

PMID:39490932 | DOI:10.1016/j.jlr.2024.100678

Metab Eng. 2024 Oct 26:S1096-7176(24)00140-X. doi: 10.1016/j.ymben.2024.10.012. Online ahead of print.

ABSTRACT

The trade-offs exist between microbial growth and bioproduct synthesis including intracellular polyester polyhydroxybutyrate (PHB). Under nitrogen limitation, more carbon flux is directed to PHB synthesis while growth is inhibited with diminishing overall carbon utilization, similar to the suboptimal carbon utilization during glycolysis-derived pyruvate decarboxylation. This study reconfigured the central carbon network of Halomonas bluphagenesis to improve PHB yield theoretically and practically. It was found that the downregulation of glutamine synthetase (GS) activity led to a synchronous improvement on PHB accumulation and cell growth under nitrogen non-limitation condition, increasing the PHB yield from glucose (g/g) to 85% of theoretical yield, PHB titer from 7.6 g/L to 12.9 g/L, and from 51 g/L to 65 g/L when grown in shake flasks containing a rich N-source, and grown in a fed-batch cultivation conducted in a 7-L bioreactor also containing a rich N-source, respectively. Results offer better metabolic balance between glucose conversion efficiency and microbial growth for economic PHB production.

PMID:39490668 | DOI:10.1016/j.ymben.2024.10.012

Pharmacol Res. 2024 Oct 26:107476. doi: 10.1016/j.phrs.2024.107476. Online ahead of print.

ABSTRACT

Cachexia affects approximately 50-80% of advanced cancer patients, particularly those with gastric cancer (GC). Therefore, early detection of cachexia is essential to prevent its progression. Targeting the gut microbiota may be a promising approach for preventing and treating cachexia in patients with GC. Chemotherapy significantly reduced gut microbiota diversity in GC patients. Specifically, the abundance of bacterial genera such as Bacteroides, Streptococcus, and Prevotella was increased in the gut of patients postchemotherapy, which was closely associated with the development of cachexia. Serum metabolic analysis revealed a strong link between specific microbes and metabolite in patients with chemotherapy-induced GC cachexia. We further constructed a random forest model based on the top 6 genera in terms of abundance for the prediction of chemotherapy-related GC cachexia development; this model had an area under the receiver operating characteristic curve (AUC) of 93.5% [95% confidence interval (CI), 86.6%-100%], with a specificity and accuracy above 75%. Additionally, we identified Enterotoxin Bacteroides fragilis (ETBF) as a key factor in chemotherapy-induced GC cachexia. In an in vivo GC model, the colonization of ETBF in the intestines of mice significantly accelerated the muscle and adipose tissue consumption induced by chemotherapy, resulting in cachexia symptoms. Furthermore, ETBF damaged the intestinal mucosal barrier by disrupting cell connections and attracting M1 macrophages, which advances GC cachexia. In conclusion, our findings indicate that gut microbiota imbalance is crucial in GC cachexia development, suggesting potential biomarkers for early diagnosis. Clinical trial registration: http://www.chictr.org.cn, Identification No: ChiCTR2200064547.

PMID:39490563 | DOI:10.1016/j.phrs.2024.107476

Arch Med Res. 2024 Nov 2;56(2):103114. doi: 10.1016/j.arcmed.2024.103114. Online ahead of print.

ABSTRACT

AIMS/HYPOTHESIS: The role of microRNAs (miRNAs) in the pathogenesis and progression of type 1 diabetes (T1D) has been described, but data remain scarce and conflicting.

OBJECTIVES: To evaluate the potential biological involvement of miRNA expression in the immune response and beta cell function in T1D.

METHODS: We screened 10 serum miRNAs from 142 subjects divided into three groups: healthy individuals (control group; n = 52) and patients at different stages of T1D progression, from the initial immunological manifestation, presenting islet cell autoantibodies (AbP group; n = 39), to partial and severe beta cell damage in T1D (recent T1D group; n = 51).

RESULTS: Three miRNAs (miR-200c-3p, miR-301a-3p, and miR-382-5p) were highly expressed in the AbP and/or recent T1D groups compared to the control group. Furthermore, in the AbP group, miR-301a-3p and miR-382-5p were positively correlated with insulin autoantibody levels and miR-382-5p was negatively correlated with C-peptide levels. In the recent T1D group, miR-200c-3p expression was positively correlated with IA-2A levels. Enrichment analysis of differentially expressed miRNAs showed their involvement in immune response, inflammatory pathways, proliferation/survival/apoptosis mechanisms, bacterial and viral infection, and insulin resistance.

CONCLUSION: Our data indicated that miR-200c-3p, miR-301a-3p, and miR-382-5p might be involved in T1D pathogenesis. Proliferative, metabolic, and immune responses were main pathways associated with serum miRNA target genes.

PMID:39489115 | DOI:10.1016/j.arcmed.2024.103114

Biochem Biophys Res Commun. 2024 Oct 26;737:150869. doi: 10.1016/j.bbrc.2024.150869. Online ahead of print.

ABSTRACT

GLABRA1 (GL1), which encodes an R2R3 MYB transcription factor, is a key regulator of trichome patterning in the aerial organs of Arabidopsis (Arabidopsis thaliana). Although it has been generally assumed that GL1 functions exclusively in shoots and is not expressed in roots, reverse transcription polymerase chain reaction (RT-PCR) analysis has revealed that GL1 is indeed expressed in roots. To investigate whether GL1 plays a role in root epidermal patterning, we analyzed the effects of gl1 mutations in sensitized genetic backgrounds. Our findings show that gl1 mutants enhance the root epidermal phenotype of a weak allele of the werewolf (wer) mutant and suppress the phenotype of the caprice (cpc) mutant. We also demonstrate that the GL1 promoter is active in N-position epidermal cells, and that the GFP-GL1 fusion protein is predominantly localized in the nucleus of N-position cells. Furthermore, we provide evidence that GL1 expression is positively regulated by WER, GLABRA3, ENHANCER OF GLABRA3, and TRANSPARENT TESTA GLABRA1, while negatively regulated by CPC, TRIPTYCHON, and GLABRA2 (GL2). Notably, GL2, which is positively regulated by GL1, moderately represses GL1 expression, and both GL1 and GL2 are positively regulated by WER in N-position cells. These findings suggest that a negative feedback regulation of GL1 expression via GL2 contributes to the fine-tuning of non-hair cell fate determination in Arabidopsis root epidermis.

PMID:39489112 | DOI:10.1016/j.bbrc.2024.150869

Clin Imaging. 2024 Oct 21;116:110334. doi: 10.1016/j.clinimag.2024.110334. Online ahead of print.

ABSTRACT

Theranostics is emerging as a critical pillar of oncologic management, as exemplified by the success of Lu-177-PSMA-617 for the treatment of castration-resistant prostate cancer. The emergence of such theranostic agents represents an opportunity to reconsider facets of nuclear medicine practice that will enable its engagement in high-volume radioligand delivery. In this article, we aim to explore simple ethical principles that can guide the development of theranostics programs as radiopharmaceutical agents proliferate and the typical nuclear medicine physician transitions from a primarily diagnostic role to a mixed diagnostic and therapeutic role. Such a mixed role will demand all the attendant competencies of direct patient care. We argue that restructuring nuclear medicine practice to meet this challenge involves developing processes for promoting the principle of fairness in patient selection for theranostic agents and for promoting the principle of responsibility during the administration of theranostic agents. We further specify that this responsibility extends to the patient receiving the therapy, the local community of the patient, and the general community exposed to the population of patients receiving theranostic agents. PRéCIS: The expansion of radioligand therapy requires promoting the ethical principle of fairness in patient selection and the ethical principle of responsibility in the delivery of radioligand therapy.

PMID:39488932 | DOI:10.1016/j.clinimag.2024.110334

STAR Protoc. 2024 Nov 2;5(4):103286. doi: 10.1016/j.xpro.2024.103286. Online ahead of print.

ABSTRACT

Proteins congregate into complexes to perform diverse cellular functions. Protein complexes are remodeled by protein-coding mutations or cellular signaling changes, driving phenotypic outcomes in health and disease. We present an affinity purification-mass spectrometry (AP-MS) proteomics protocol to express affinity-tagged "bait" proteins in mammalian cells, identify and quantify purified protein interactors, and visualize differential protein-protein interaction networks between pairwise conditions. Our protocol possesses general applicability to various cell types and biological areas. For complete details on the use and execution of this protocol, please refer to Bouhaddou et al.1.

PMID:39488835 | DOI:10.1016/j.xpro.2024.103286

Gut Microbes. 2024 Jan-Dec;16(1):2420771. doi: 10.1080/19490976.2024.2420771. Epub 2024 Nov 3.

ABSTRACT

Probiotics hold great potential for treating metabolic diseases such as obesity. Given the complex and multifactorial nature of these diseases, research on probiotic combination with multiple targets has become popular. Here, we choose four obesity-related targets to perform high-throughput screening, including pancreatic lipase activity, bile salt hydrolase activity, glucagon-like peptide-1 secretion and adipocyte differentiation. Then, we obtained 649 multi-strain combinations with the requirement that each must cover all these targets in principle. After in vitro co-culture and in vivo co-colonization experiments, only four (<0.7%) combinations were selected as symbiotic probiotic communities (SPCs). Next, genome-scale metabolic model analysis revealed that these SPCs showed lower metabolic resource overlap and higher metabolic interaction potential involving amino acid metabolism (Ammonium, L-Lysine, etc.) and energy metabolism (Phosphate, etc.). Further animal experiments demonstrated that all SPCs exhibited a good safety profile and excellent effects in improving obesity and associated glucose metabolism disruptions and depression-like behaviors in high-fat-diet-fed mice. This anti-obesity improvement was achieved through reduced cholesterol level, fat accumulation and inhibited adipocyte differentiation. Taken together, our study provides a new perspective for designing multi-strain combinations, which may facilitate greater therapeutic effect on obesity and other complex diseases in the future.

PMID:39488738 | DOI:10.1080/19490976.2024.2420771

Crit Rev Biochem Mol Biol. 2024 Nov 3:1-26. doi: 10.1080/10409238.2024.2418639. Online ahead of print.

ABSTRACT

Space exploration and research are uncovering the potential for terrestrial life to survive in outer space, as well as the environmental factors that affect life during interplanetary transfer. The presence of methane in the Martian atmosphere suggests the possibility of methanogens, either extant or extinct, on Mars. Understanding how methanogens survive and adapt under space-exposed conditions is crucial for understanding the implications of extraterrestrial life. In this article, we discuss methanogens as model organisms for obtaining energy transducers and producing methane in a simulated Martian environment. We also explore the chemical evolution of cellular composition and growth maintenance to support survival in extraterrestrial environments. Neutral selective pressure is imposed on the chemical composition of cellular components to increase cell survival and reduce growth under physiological conditions. Energy limitation is an evolutionary driver of macromolecular polymerization, growth maintenance, and survival fitness of methanogens. Methanogens grown in a Martian environment may exhibit global alterations in their metabolic function and gene expression at the system scale. A space systems biology approach would further elucidate molecular survival mechanisms and adaptation to a drastic outer space environment. Therefore, identifying a genetically stable methanogenic community is essential for biomethane production from waste recycling to achieve sustainable space-life support functions.

PMID:39488737 | DOI:10.1080/10409238.2024.2418639

Eur J Surg Oncol. 2024 Oct 24:108783. doi: 10.1016/j.ejso.2024.108783. Online ahead of print.

ABSTRACT

Endometrial cancer (EC) is increasing incidence among women, and it constitutes a health problem for women globally. An important aspect of EC management involves the use of protein biomarkers for early detection and monitoring. Protein biomarkers allow the identification of high-risk patients, the detection of the disease in its early stages, and the assessment of treatment responses. Mass spectrometry (MS)-based proteomics offers robust analytical techniques and a comprehensive understanding of proteins. Proteomics methods allow scientists to investigate both the quantities and functions of proteins. Thus, it provides valuable insights into how proteins are altered under different conditions. This review summarizes recent advances in MS-based proteomic biomarker discovery for EC, focusing on different sample types and MS-based techniques used in clinical studies. The review emphasized in detail the most commonly used key sources such as blood, urine, vaginal fluids and tissue. Furthermore, MS-based proteomics techniques such as untargeted, targeted, sequential window acquisition of all theoretical mass spectra (SWATH-MS) and mass spectrometry imaging used in the discovery and validation/validation phases were evaluated. This review highlights the importance of biomarker discovery and clinical translation to improve diagnostic and therapeutic outcomes in EC. It aims to provide a comprehensive overview of MS-based proteomics in EC, guiding future research and clinical applications.

PMID:39488491 | DOI:10.1016/j.ejso.2024.108783

Cell Genom. 2024 Oct 24:100691. doi: 10.1016/j.xgen.2024.100691. Online ahead of print.

ABSTRACT

The insufficient availability of comprehensive protein-level perturbation data is impeding the widespread adoption of systems biology. In this perspective, we introduce the rationale, essentiality, and practicality of perturbation proteomics. Biological systems are perturbed with diverse biological, chemical, and/or physical factors, followed by proteomic measurements at various levels, including changes in protein expression and turnover, post-translational modifications, protein interactions, transport, and localization, along with phenotypic data. Computational models, employing traditional machine learning or deep learning, identify or predict perturbation responses, mechanisms of action, and protein functions, aiding in therapy selection, compound design, and efficient experiment design. We propose to outline a generic PMMP (perturbation, measurement, modeling to prediction) pipeline and build foundation models or other suitable mathematical models based on large-scale perturbation proteomic data. Finally, we contrast modeling between artificially and naturally perturbed systems and highlight the importance of perturbation proteomics for advancing our understanding and predictive modeling of biological systems.

PMID:39488205 | DOI:10.1016/j.xgen.2024.100691

Mar Environ Res. 2024 Oct 29;202:106819. doi: 10.1016/j.marenvres.2024.106819. Online ahead of print.

ABSTRACT

Back-reef habitats are important and fragile transition zones acting as nurseries for many coral reef fishes. In this framework, Passive Acoustic Monitoring (PAM) can be an important tool to evaluate the diversity and dynamics of sonic fish community. Here, we investigated the diversity, spatial and diel dynamics of fish sounds in back-reef habitats at Makogai Island in Fiji, South Pacific. Synchronized underwater recorders were deployed in 4 bays collecting data for about 4 days. The abundance of 12 different sub-categories of fish sounds were quantified. Signals were acoustically characterized and the level of discrimination between the sub-categories was evaluated by Discrimination Function Analysis. Generalized Additive Models showed that the abundance of signals was related to the bay and the hour. Moreover, the Shannon Diversity and Equitability Indices were calculated using acoustic and visual census data to describe fish biodiversity of each bay. The two bays with greater biodiversity based on visual census also showed a greater acoustic diversity at dawn and night. Our results highlight the importance of PAM to reveal the diversity of fish community in back-reef habitats, providing a baseline to understand future changes in these crucial environments.

PMID:39488099 | DOI:10.1016/j.marenvres.2024.106819

Microb Biotechnol. 2024 Nov;17(11):e70027. doi: 10.1111/1751-7915.70027.

ABSTRACT

Artificial intelligence (AI) has the potential to transform clinical practice and healthcare. Following impressive advancements in fields such as computer vision and medical imaging, AI is poised to drive changes in microbiome-based healthcare while facing challenges specific to the field. This review describes the state-of-the-art use of AI in microbiome-related healthcare. It points out limitations across topics such as data handling, AI modelling and safeguarding patient privacy. Furthermore, we indicate how these current shortcomings could be overcome in the future and discuss the influence and opportunities of increasingly complex data on microbiome-based healthcare.

PMID:39487766 | DOI:10.1111/1751-7915.70027

Liver Int. 2024 Nov 2. doi: 10.1111/liv.16150. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Glucagon-like peptide-1 receptor (GLP1R) agonists and glucose-dependent insulinotropic polypeptide receptor (GIPR) agonists may help treat metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH). However, their definitive effects are still unclear. Our study aims to clarify this uncertainty.

METHODS: We utilised conventional Mendelian randomisation (MR) analysis to explore potential causal links between plasma GLP-1/GIP concentrations and MASLD and its related traits. Next, we conducted drug-target MR analysis using highly expressed tissue data to assess the effects of corresponding drug perturbation on these traits. Finally, mediation analysis was performed to ascertain whether the potential causal effect is direct or mediated by other MASLD-related traits.

RESULTS: Circulating 2-h GLP-1 and GIP concentrations measured during an oral glucose tolerance test showed hepatoprotective effects on MASLD risk (ORGLP-1 = 0.168 [95% CI 0.033-0.839], p = 0.030; ORGIP = 0.331 [95% CI 0.222-0.494], p = 6.31 × 10-8). GLP1R expression in the blood had a minimal causal effect on MASLD risk, whereas GIPR expression significantly affected MASLD risk (OR = 0.671 [95% CI 0.531-0.849], p = 9.07 × 10-4). Expression levels of GLP1R or GIPR in the blood significantly influenced MASLD-related clinical traits. Mediation analysis revealed that GIPR expression protected against MASLD, even after adjusting for type 2 diabetes or body mass index.

CONCLUSIONS: GLP-1/GIP receptor agonists offer promise in lowering MASLD/MASH risk. GIP receptor agonists can exert direct and indirect effects on MASLD mediated by weight reduction or glycemic control improvement.

PMID:39487684 | DOI:10.1111/liv.16150

Sci Rep. 2024 Nov 1;14(1):26328. doi: 10.1038/s41598-024-76773-4.

ABSTRACT

Water scarcity has evolved into a pressing global issue, significantly impacting numerous regions worldwide. The use of treated wastewater stands out as a promising solution to this problem. However, the proliferation of various contaminants, primarily Antimicrobial Resistance Genes (ARGs), poses a significant challenge to its safe and sustainable use. In this study, we assessed the composition and abundance of 373 ARGs, corresponding to 31 different classes of antibiotics, in six wastewater treatment plants (WWTP) in Agadir city of Morocco. Influent and effluent samples were collected during the months of February and July in 2020, in addition to samples from the Atlantic Ocean. In total, 223 ARGs were uncovered, highlighting in particular resistance to aminoglycoside, macrolide lincosamide, beta-lactamase, chloramphenicol, sulfonamide, tetracycline, and other antibiotics. The mechanisms of action of these ARGs were mainly antibiotic inactivation, antibiotic target alteration, efflux pump and cellular protection. Mobile genetic elements (MGEs) were detected at high levels their co-occurrence with ARGs highlights their involvement in the acquisition and transmission of ARGs in microbial communities through horizontal gene transfer. While many wastewater treatment methods effectively reduce a large proportion of gene material and pathogens, a substantial fraction of ARGs and other contaminants persist in treated wastewater. This persistence poses potential risks to both human health and the environment, warranting the need of more effective treatment strategies.

PMID:39487157 | DOI:10.1038/s41598-024-76773-4