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1.
J Environ Sci (China) ; 147: 310-321, 2025 Jan.
Article de Anglais | MEDLINE | ID: mdl-39003049

RÉSUMÉ

In this study, the effects of different salinity gradients and addition of compatible solutes on anaerobic treated effluent water qualities, sludge characteristics and microbial communities were investigated. The increase in salinity resulted in a decrease in particle size of the granular sludge, which was concentrated in the range of 0.5-1.0 mm. The content of EPS (extracellular polymeric substances) in the granular sludge gradually increased with increasing salinity and the addition of betaine (a typical compatible solute). Meanwhile, the microbial community structure was significantly affected by salinity, with high salinity reducing the diversity of bacteria. At higher salinity, Patescibacteria and Proteobacteria gradually became the dominant phylum, with relative abundance increasing to 13.53% and 12.16% at 20 g/L salinity. Desulfobacterota and its subordinate Desulfovibrio, which secrete EPS in large quantities, dominated significantly after betaine addition.Their relative abundance reached 13.65% and 7.86% at phylum level and genus level. The effect of these changes on the treated effluent was shown as the average chemical oxygen demand (COD) removal rate decreased from 82.10% to 79.71%, 78.01%, 68.51% and 64.55% when the salinity gradually increased from 2 g/L to 6, 10, 16 and 20 g/L. At the salinity of 20 g/L, average COD removal increased to 71.65% by the addition of 2 mmol/L betaine. The gradient elevated salinity and the exogenous addition of betaine played an important role in achieving stability of the anaerobic system in a highly saline environment, which provided a feasible strategy for anaerobic treatment of organic saline wastewater.


Sujet(s)
Bétaïne , Salinité , Eaux d'égout , Élimination des déchets liquides , Eaux usées , Bétaïne/métabolisme , Eaux d'égout/microbiologie , Élimination des déchets liquides/méthodes , Eaux usées/composition chimique , Anaérobiose , Microbiote/effets des médicaments et des substances chimiques , Bactéries/métabolisme , Bactéries/effets des médicaments et des substances chimiques
2.
Bull Environ Contam Toxicol ; 113(1): 3, 2024 Jul 04.
Article de Anglais | MEDLINE | ID: mdl-38965095

RÉSUMÉ

Sanitary leachate from urban landfills is known to be contaminated with multi-metals and residual antibiotics. Current research edges on exploring the multi-metal and antibiotic sensitivity profile of four indigenous strains, "Brevibacillus spp. Leclercia spp. Pseudescherichia spp., and Brucella spp." isolated from the leachate of a sanitary landfill in a tropical region. Indigenous isolates were observed to be antibiotic-resistant and have high tolerance against eight of the ten tested metals except Cu & Co. It was observed that interaction with multi-metals in laboratory conditions significantly altered the cell morphology of bacterial strains, as depicted by Scanning Electron Microscope. Metal adsorption onto the microbial surface was deciphered through Electron Dispersive Spectrometer analysis and elemental mapping. Application of isolated strains into real-time leachate matrix exhibits a complete reduction of Ag and Zn and for other tested metals. Their response to these toxicants may facilitate their application in bioremediation-based treatment technologies for urban landfill leachate.


Sujet(s)
Antibactériens , Dépollution biologique de l'environnement , Métaux lourds , Installations d'élimination des déchets , Polluants chimiques de l'eau , Antibactériens/pharmacologie , Bactéries/effets des médicaments et des substances chimiques
3.
Chem Biol Drug Des ; 104(1): e14573, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38965664

RÉSUMÉ

Infectious diseases have been jeopardized problem that threaten public health over a long period of time. The growing prevalence of drug-resistant pathogens and infectious cases have led to a decrease in the number of effective antibiotics, which highlights the urgent need for the development of new antibacterial agents. Serine acetyltransferase (SAT), also known as CysE in certain bacterial species, and O-acetylserine sulfhydrylase (OASS), also known as CysK in select bacteria, are indispensable enzymes within the cysteine biosynthesis pathway of various pathogenic microorganisms. These enzymes play a crucial role in the survival of these pathogens, making SAT and OASS promising targets for the development of novel anti-infective agents. In this comprehensive review, we present an introduction to the structure and function of SAT and OASS, along with an overview of existing inhibitors for SAT and OASS as potential antibacterial agents. Our primary focus is on elucidating the inhibitory activities, structure-activity relationships, and mechanisms of action of these inhibitors. Through this exploration, we aim to provide insights into promising strategies and prospects in the development of antibacterial agents that target these essential enzymes.


Sujet(s)
Antibactériens , O-acetylserine(thiol)-lyase , Cystéine , Antienzymes , Serine O-acetyltransferase , Serine O-acetyltransferase/métabolisme , Serine O-acetyltransferase/composition chimique , Serine O-acetyltransferase/antagonistes et inhibiteurs , Antienzymes/composition chimique , Antienzymes/pharmacologie , Antienzymes/métabolisme , Cystéine/métabolisme , Cystéine/composition chimique , Cystéine/biosynthèse , Antibactériens/composition chimique , Antibactériens/pharmacologie , Antibactériens/biosynthèse , O-acetylserine(thiol)-lyase/métabolisme , O-acetylserine(thiol)-lyase/antagonistes et inhibiteurs , Relation structure-activité , Humains , Bactéries/enzymologie , Bactéries/effets des médicaments et des substances chimiques , Bactéries/métabolisme
4.
PeerJ ; 12: e17461, 2024.
Article de Anglais | MEDLINE | ID: mdl-38952992

RÉSUMÉ

Agricultural soils contaminated with heavy metals poison crops and disturb the normal functioning of rhizosphere microbial communities. Different crops and rhizosphere microbial communities exhibit different heavy metal resistance mechanisms. Here, indoor pot studies were used to assess the mechanisms of grain and soil rhizosphere microbial communities on chromium (Cr) stress. Millet grain variety 'Jingu 21' (Setaria italica) and soil samples were collected prior to control (CK), 6 hours after (Cr_6h), and 6 days following (Cr_6d) Cr stress. Transcriptomic analysis, high-throughput sequencing and quantitative polymerase chain reaction (qPCR) were used for sample determination and data analysis. Cr stress inhibited the expression of genes related to cell division, and photosynthesis in grain plants while stimulating the expression of genes related to DNA replication and repair, in addition to plant defense systems resist Cr stress. In response to chromium stress, rhizosphere soil bacterial and fungal community compositions and diversity changed significantly (p < 0.05). Both bacterial and fungal co-occurrence networks primarily comprised positively correlated edges that would serve to increase community stability. However, bacterial community networks were larger than fungal community networks and were more tightly connected and less modular than fungal networks. The abundances of C/N functional genes exhibited increasing trends with increased Cr exposure. Overall, these results suggest that Cr stress primarily prevented cereal seedlings from completing photosynthesis, cell division, and proliferation while simultaneously triggering plant defense mechanisms to resist the toxic effects of Cr. Soil bacterial and fungal populations exhibited diverse response traits, community-assembly mechanisms, and increased expression of functional genes related to carbon and nitrogen cycling, all of which are likely related to microbial survival during Cr stress. This study provides new insights into resistance mechanisms, microbial community structures, and mechanisms of C/N functional genes responses in cereal plants to heavy metal contaminated agricultural soils. Portions of this text were previously published as part of a preprint (https://www.researchsquare.com/article/rs-2891904/v1).


Sujet(s)
Chrome , Grains comestibles , Rhizosphère , Microbiologie du sol , Polluants du sol , Chrome/toxicité , Chrome/effets indésirables , Chrome/métabolisme , Polluants du sol/toxicité , Polluants du sol/effets indésirables , Grains comestibles/microbiologie , Stress physiologique/effets des médicaments et des substances chimiques , Champignons/effets des médicaments et des substances chimiques , Champignons/génétique , Microbiote/effets des médicaments et des substances chimiques , Bactéries/génétique , Bactéries/effets des médicaments et des substances chimiques , Bactéries/métabolisme
5.
Front Immunol ; 15: 1298971, 2024.
Article de Anglais | MEDLINE | ID: mdl-38953021

RÉSUMÉ

Introduction: More than 350,000 chemicals make up the chemical universe that surrounds us every day. The impact of this vast array of compounds on our health is still poorly understood. Manufacturers are required to carry out toxicological studies, for example on the reproductive or nervous systems, before putting a new substance on the market. However, toxicological safety does not exclude effects resulting from chronic exposure to low doses or effects on other potentially affected organ systems. This is the case for the microbiome-immune interaction, which is not yet included in any safety studies. Methods: A high-throughput in vitro model was used to elucidate the potential effects of environmental chemicals and chemical mixtures on microbiome-immune interactions. Therefore, a simplified human intestinal microbiota (SIHUMIx) consisting of eight bacterial species was cultured in vitro in a bioreactor that partially mimics intestinal conditions. The bacteria were continuously exposed to mixtures of representative and widely distributed environmental chemicals, i.e. bisphenols (BPX) and/or per- and polyfluoroalkyl substances (PFAS) at concentrations of 22 µM and 4 µM, respectively. Furthermore, changes in the immunostimulatory potential of exposed microbes were investigated using a co-culture system with human peripheral blood mononuclear cells (PBMCs). Results: The exposure to BPX, PFAS or their mixture did not influence the community structure and the riboflavin production of SIHUMIx in vitro. However, it altered the potential of the consortium to stimulate human immune cells: in particular, activation of CD8+ MAIT cells was affected by the exposure to BPX- and PFAS mixtures-treated bacteria. Discussion: The present study provides a model to investigate how environmental chemicals can indirectly affect immune cells via exposed microbes. It contributes to the much-needed knowledge on the effects of EDCs on an organ system that has been little explored in this context, especially from the perspective of cumulative exposure.


Sujet(s)
Microbiome gastro-intestinal , Phénols , Humains , Microbiome gastro-intestinal/effets des médicaments et des substances chimiques , Microbiome gastro-intestinal/immunologie , Phénols/toxicité , Composés benzhydryliques/toxicité , Fluorocarbones , Agranulocytes/immunologie , Agranulocytes/effets des médicaments et des substances chimiques , Agranulocytes/métabolisme , Techniques de coculture , Polluants environnementaux/toxicité , Bactéries/effets des médicaments et des substances chimiques , Bactéries/immunologie
6.
Sci Rep ; 14(1): 15441, 2024 07 04.
Article de Anglais | MEDLINE | ID: mdl-38965246

RÉSUMÉ

A very practical method for the synthesis of unsymmetrical carbamide derivatives in good to excellent yield was presented, without the need for any catalyst and at room temperature. Using a facile and robust protocol, fifteen unsymmetrical carbamide derivatives (9-23) bearing different aliphatic amine moieties were designed and synthesized by the reaction of secondary aliphatic amines with isocyanate derivatives in the presence of acetonitrile as an appropriate solvent in good to excellent yields. Trusted instruments like IR, mass spectrometry, NMR spectra, and elemental analyses were employed to validate the purity and chemical structures of the synthesized compounds. All the synthesized compounds were tested as antimicrobial agents against some clinically bacterial pathogens such as Salmonella typhimurium, Bacillus subtilis, Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans. Compounds 15, 16, 17, 19 and 22 showed potent antimicrobial activity with promising MIC values compared to the positive controls. Moreover, compounds 15 and 22 provide a potent lipid peroxidation (LPO) of the bacterial cell wall. On the other hand, we investigated the anti-proliferative activity of compounds 9-23 against selected human cancerous cell lines of breast (MCF-7), colon (HCT-116), and lung (A549) relative to healthy noncancerous control skin fibroblast cells (BJ-1). The mechanism of their cytotoxic activity has been also examined by immunoassaying the levels of key anti- and pro-apoptotic protein markers. The results of MTT assay revealed that compounds 10, 13, 21, 22 and 23 possessed highly cytotoxic effects. Out of these, three synthesized compounds 13, 21 and 22 showed cytotoxicity with IC50 values (13, IC50 = 62.4 ± 0.128 and 22, IC50 = 91.6 ± 0.112 µM, respectively, on MCF-7), (13, IC50 = 43.5 ± 0.15 and 21, IC50 = 38.5 ± 0.17 µM, respectively, on HCT-116). Cell cycle and apoptosis/necrosis assays demonstrated that compounds 13 and 22 induced S and G2/M phase cell cycle arrest in MCF-7 cells, while only compound 13 had this effect on HCT-116 cells. Furthermore, compound 13 exhibited the greatest potency in inducing apoptosis in both cell lines compared to compounds 21 and 22. Docking studies indicated that compounds 10, 13, 21 and 23 could potentially inhibit enzymes and exert promising antimicrobial effects, as evidenced by their lower binding energies and various types of interactions observed at the active sites of key enzymes such as Sterol 14-demethylase of C. albicans, Dihydropteroate synthase of S. aureus, LasR of P. aeruginosa, Glucosamine-6-phosphate synthase of K. pneumenia and Gyrase B of B. subtilis. Moreover, 13, 21, and 22 demonstrated minimal binding energy and favorable affinity towards the active pocket of anticancer receptor proteins, including CDK2, EGFR, Erα, Topoisomerase II and VEGFFR. Physicochemical properties, drug-likeness, and ADME (absorption, distribution, metabolism, excretion, and toxicity) parameters of the selected compounds were also computed.


Sujet(s)
Anti-infectieux , Antinéoplasiques , Tests de sensibilité microbienne , Humains , Antinéoplasiques/pharmacologie , Antinéoplasiques/synthèse chimique , Antinéoplasiques/composition chimique , Anti-infectieux/pharmacologie , Anti-infectieux/synthèse chimique , Anti-infectieux/composition chimique , Lignée cellulaire tumorale , Apoptose/effets des médicaments et des substances chimiques , Technologie de la chimie verte/méthodes , Prolifération cellulaire/effets des médicaments et des substances chimiques , Candida albicans/effets des médicaments et des substances chimiques , Simulation de docking moléculaire , Cellules MCF-7 , Antibactériens/pharmacologie , Antibactériens/synthèse chimique , Antibactériens/composition chimique , Staphylococcus aureus/effets des médicaments et des substances chimiques , Bactéries/effets des médicaments et des substances chimiques , Pseudomonas aeruginosa/effets des médicaments et des substances chimiques
7.
Appl Microbiol Biotechnol ; 108(1): 406, 2024 Jul 03.
Article de Anglais | MEDLINE | ID: mdl-38958764

RÉSUMÉ

The proliferation and dissemination of antimicrobial-resistant bacteria is an increasingly global challenge and is attributed mainly to the excessive or improper use of antibiotics. Currently, the gold-standard phenotypic methodology for detecting resistant strains is agar plating, which is a time-consuming process that involves multiple subculturing steps. Genotypic analysis techniques are fast, but they require pure starting samples and cannot differentiate between viable and non-viable organisms. Thus, there is a need to develop a better method to identify and prevent the spread of antimicrobial resistance. This work presents a novel method for detecting and identifying antibiotic-resistant strains by combining a cell sorter for bacterial detection and an elastic-light-scattering method for bacterial classification. The cell sorter was equipped with safety mechanisms for handling pathogenic organisms and enabled precise placement of individual bacteria onto an agar plate. The patterning was performed on an antibiotic-gradient plate, where the growth of colonies in sections with high antibiotic concentrations confirmed the presence of a resistant strain. The antibiotic-gradient plate was also tested with an elastic-light-scattering device where each colony's unique colony scatter pattern was recorded and classified using machine learning for rapid identification of bacteria. Sorting and patterning bacteria on an antibiotic-gradient plate using a cell sorter reduced the number of subculturing steps and allowed direct qualitative binary detection of resistant strains. Elastic-light-scattering technology is a rapid, label-free, and non-destructive method that permits instantaneous classification of pathogenic strains based on the unique bacterial colony scatter pattern. KEY POINTS: • Individual bacteria cells are placed on gradient agar plates by a cell sorter • Laser-light scatter patterns are used to recognize antibiotic-resistant organisms • Scatter patterns formed by colonies correspond to AMR-associated phenotypes.


Sujet(s)
Antibactériens , Résistance bactérienne aux médicaments , Phénotype , Antibactériens/pharmacologie , Bactéries/effets des médicaments et des substances chimiques , Bactéries/génétique , Bactéries/classification , Cytométrie en flux/méthodes , Tests de sensibilité microbienne/méthodes , Lumière
8.
PLoS One ; 19(7): e0300643, 2024.
Article de Anglais | MEDLINE | ID: mdl-38954725

RÉSUMÉ

As most teleosts are unable to synthesize vitamin C, supplemental diets containing vitamin C diets play a crucial role in fish health. The aim of this study was to investigate the effect of dietary vitamin C on the intestinal enzyme activity and intestinal microbiota of silver pomfre (Pampus argenteus). Four experimental diets were supplemented with basic diets containing 300 mg of vitamin C/kg (group tjl3), 600 mg of vitamin C/kg (group tjl6), and 1200 mg of vitamin C/kg (group tjl12), as well as vitamin C-free supplemental basic diet (group tjl0), respectively. The four diets were fed to juvenile P. argenteus (average initial weight: 4.68 ± 0.93 g) for 6 weeks. The results showed that the activity of SOD (superoxide dismutase) and CAT (catalase) increased significantly while that of MDA (malondialdehyde) decreased significantly in group tjl3 compared to vitamin group tjl0. At the genus level, groups tjl0, tjl6, and tjl12 contained the same dominant microbial community, Stenotrophomonas, Photobacterium, and Vibrio, whereas group tjl3 was dominated by Stenotrophomonas, Delftia, and Bacteroides. Among the fish fed with a basic diet containing 300 mg of vitamin C/kg, the intestines exhibited a notable abundance of probiotic bacteria, including lactic acid bacteria (Lactobacillus) and Bacillus. The abundance of Aeromonas in groups tjl3 and tjl6 was lower than that of the vitamin C-free supplemental basic diet group, whereas Aeromonas was not detected in group tjl12. In addition, a causative agent of the disease outbreak in cultured P. argenteus, Photobacterium damselae subsp. Damselae (PDD) was the dominant microbiota community in groups tjl0, tjl6 and tjl12, whereas the abundance of PDD in group tjl3 was the lowest among the diets. Taken together, the diets supplied with vitamin C could influence the composition microbial community of P. argenteus. The low level of vitamin C (300 mg of vitamin C/kg per basic diet) supplementation could not only improve the antioxidant capacity but also resist the invasion of pathogenic bacteria.


Sujet(s)
Antioxydants , Acide ascorbique , Compléments alimentaires , Microbiome gastro-intestinal , Animaux , Acide ascorbique/pharmacologie , Microbiome gastro-intestinal/effets des médicaments et des substances chimiques , Antioxydants/pharmacologie , Antioxydants/métabolisme , Perciformes/microbiologie , Aliment pour animaux/analyse , Superoxide dismutase/métabolisme , Bactéries/effets des médicaments et des substances chimiques , Bactéries/isolement et purification , Régime alimentaire/médecine vétérinaire , Catalase/métabolisme
9.
Benef Microbes ; 15(4): 357-371, 2024 Jul 02.
Article de Anglais | MEDLINE | ID: mdl-38955353

RÉSUMÉ

Constipation during pregnancy can induce serious complications, including miscarriage and preterm labour, while the evidence of probiotics in improving constipation during pregnancy was little. In this study, 29 healthy pregnant women and 65 constipated pregnant women were enrolled to assess the effectiveness of probiotics on constipation during pregnancy. Our results showed that the probiotics were effective in improving the Constipation Severity Scale (CSS) and Bristol Stool Scale (BSS) scores, including increasing defecation frequency, decreasing defecation time, and improving fecal characteristics. 16S rRNA sequencing revealed that the probiotics effectively restored the diversity of intestinal microbiota. At the phylum level, Firmicutes (13.27% vs 57.20%) and Actinobacteria (3.77% vs 12.80%) were increased, while Bacteroidetes (77.82% vs 20.24%) was decreased. At the level of the genus, Faecalibacterium (2.03% vs 10.33%), Bifidobacterium (1.21% vs 8.56%), and Phascolarctobacterium (0.05% vs 2.88%), the beneficial bacteria were increased, while the Bacteroides (29.23% vs 12.28%) and Prevotella (24.32% vs 4.92%) were decreased. In conclusion, these results indicated that probiotics can effectively relieve the constipation symptoms by improving the diversity of intestinal microbiota, regulating the disturbance of microflorae, and restoring the balance of microflorae to exert a stronger moderating effect than diet and lifestyle modification. Our results provided clinical data and a theoretical basis for the exploitation of probiotics in treating constipation during pregnancy. Chinese Clinical Trial Registry: ChiCTR2100052069.


Sujet(s)
Constipation , Fèces , Microbiome gastro-intestinal , Probiotiques , ARN ribosomique 16S , Constipation/thérapie , Constipation/microbiologie , Constipation/traitement médicamenteux , Humains , Femelle , Probiotiques/administration et posologie , Probiotiques/usage thérapeutique , Grossesse , Microbiome gastro-intestinal/effets des médicaments et des substances chimiques , Adulte , Fèces/microbiologie , ARN ribosomique 16S/génétique , Bactéries/classification , Bactéries/génétique , Bactéries/effets des médicaments et des substances chimiques , Bactéries/isolement et purification , Complications de la grossesse/microbiologie , Complications de la grossesse/thérapie , Complications de la grossesse/traitement médicamenteux , Jeune adulte , Défécation/effets des médicaments et des substances chimiques
10.
Cell Host Microbe ; 32(7): 1037-1039, 2024 Jul 10.
Article de Anglais | MEDLINE | ID: mdl-38991497

RÉSUMÉ

New therapies to treat multi-drug-resistant (MDR) pathogens are needed. Santos-Júnior et al. discover new antimicrobials by leveraging the history of warfare within microbial communities. This study in Cell highlights the immense power of combining large biological databases with emerging computational methods, creating a key resource (AMPSphere) to be used for treating superbugs.


Sujet(s)
Antibactériens , Humains , Antibactériens/pharmacologie , Multirésistance bactérienne aux médicaments/génétique , Bactéries/génétique , Bactéries/effets des médicaments et des substances chimiques , Biologie informatique/méthodes
11.
J Environ Manage ; 365: 121632, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-38950506

RÉSUMÉ

Hermetia illucens larvae showcases remarkable bioremediation capabilities for both antibiotics and heavy metal contaminants. However, the distinctions in larval intestinal microbiota arising from the single and combined effects of antibiotics and heavy metals remain poorly elucidated. In this study, we delved into the details of larval intestinal bacterial communities and microbial metabolites when exposed to single and combined contaminants of oxytetracycline (OTC) and hexavalent chromium (Cr(VI)). After conversion, single contaminant-spiked substrate showed 75.5% of OTC degradation and 95.2% of Cr(VI) reductiuon, while combined contaminant-spiked substrate exhibited 71.3% of OTC degradation and 93.4% of Cr(VI) reductiuon. Single and combined effects led to differences in intestinal bacterial communities, mainly reflected in the genera of Enterococcus, Pseudogracilibacillus, Gracilibacillus, Wohlfahrtiimonas, Sporosarcina, Lysinibacillus, and Myroide. Moreover, these effects also induced differences across various categories of microbial metabolites, which categorized into amino acid and its metabolites, benzene and substituted derivatives, carbohydrates and its metabolites, heterocyclic compounds, hormones and hormone-related compounds, nucleotide and its metabolites, and organic acid and its derivatives. In particular, the differences induced OTC was greater than that of Cr(VI), and combined effects increased the complexity of microbial metabolism compared to that of single contaminant. Correlation analysis indicated that the bacterial genera, Preudogracilibacillus, Enterococcus, Sporosarcina, Lysinibacillus, Wohlfahrtiimonas, Ignatzschineria, and Fusobacterium exhibited significant correlation with significant differential metabolites, these might be used as indicators for the resistance and bioremediation of OTC and Cr(VI) contaminants. These findings are conducive to further understanding that the metabolism of intestinal microbiota determines the resistance of Hermetia illucens to antibiotics and heavy metals.


Sujet(s)
Antibactériens , Dépollution biologique de l'environnement , Microbiome gastro-intestinal , Larve , Métaux lourds , Animaux , Antibactériens/pharmacologie , Larve/effets des médicaments et des substances chimiques , Larve/croissance et développement , Microbiome gastro-intestinal/effets des médicaments et des substances chimiques , Bactéries/métabolisme , Bactéries/effets des médicaments et des substances chimiques , Chrome/métabolisme
12.
Methods Mol Biol ; 2833: 35-42, 2024.
Article de Anglais | MEDLINE | ID: mdl-38949698

RÉSUMÉ

Antimicrobial resistance (AMR) poses a serious threat to global health, potentially causing 10 million deaths per year globally by 2050. To tackle AMR, researchers from all around the world have generated a selection of various formulated (viz. nanoparticulate, liposomal) therapeutic combinations to be evaluated for new antimicrobial drug discovery. To meet the urgent need for accelerating new antibacterial drug development, we need rapid but reliable whole-cell assay methods and models to test formulated therapeutic combinations against several pathogens in different in vitro conditions as models of actual infections.Over the past two decades, high-throughput spot-culture growth inhibition assay (HT-SPOTi) has been demonstrated to be a gold-standard drug susceptibility method for evaluating novel chemotherapeutic entities and existing drugs against various microbes of global concern. Our modified HT-SPOTi method serves the purpose of evaluating drug combinations against Gram-positive/negative microorganisms as well as acid-fast bacilli. The newly developed and modified HT-SPOTi assay builds upon the limitations of our previously published method to incorporate antimicrobial susceptibility testing with formulated therapeutic combinations. The modified HT-SPOTi is compared with a range of other antimicrobial susceptibility testing methods and validated using a library of existing antibiotics as well as formulated therapeutic combinations. The modified HT-SPOTi assay can serve as an efficient and reliable high-throughput drug screening platform to discover new potential antimicrobial molecules, including as part of therapeutic formulations.This chapter describes the generation of drug susceptibility profile for formulated therapeutic combinations using modified HT-SPOTi in a semi-automated system.


Sujet(s)
Antibactériens , Tests de sensibilité microbienne , Tests de sensibilité microbienne/méthodes , Antibactériens/pharmacologie , Tests de criblage à haut débit/méthodes , Humains , Bactéries/effets des médicaments et des substances chimiques , Bactéries/croissance et développement
13.
Methods Mol Biol ; 2833: 93-108, 2024.
Article de Anglais | MEDLINE | ID: mdl-38949704

RÉSUMÉ

To model complex systems, individual-based models (IBMs), sometimes called "agent-based models" (ABMs), describe a simplification of the system through an adequate representation of the elements. IBMs simulate the actions and interaction of discrete individuals/agents within a system in order to discover the pattern of behavior that comes from these interactions. Examples of individuals/agents in biological systems are individual immune cells and bacteria that act independently with their own unique attributes defined by behavioral rules. In IBMs, each of these agents resides in a spatial environment and interactions are guided by predefined rules. These rules are often simple and can be easily implemented. It is expected that following the interaction guided by these rules we will have a better understanding of agent-agent interaction as well as agent-environment interaction. Stochasticity described by probability distributions must be accounted for. Events that seldom occur such as the accumulation of rare mutations can be easily modeled.Thus, IBMs are able to track the behavior of each individual/agent within the model while also obtaining information on the results of their collective behaviors. The influence of impact of one agent with another can be captured, thus allowing a full representation of both direct and indirect causation on the aggregate results. This means that important new insights can be gained and hypotheses tested.


Sujet(s)
Résistance microbienne aux médicaments , Humains , Résistance microbienne aux médicaments/génétique , Antibactériens/pharmacologie , Modèles théoriques , Bactéries/génétique , Bactéries/effets des médicaments et des substances chimiques , Interactions hôte-pathogène , Résistance bactérienne aux médicaments/génétique , Modèles biologiques , Simulation numérique
14.
Methods Mol Biol ; 2833: 79-91, 2024.
Article de Anglais | MEDLINE | ID: mdl-38949703

RÉSUMÉ

Mathematical models have been used to study the spread of infectious diseases from person to person. More recently studies are developing within-host modeling which provides an understanding of how pathogens-bacteria, fungi, parasites, or viruses-develop, spread, and evolve inside a single individual and their interaction with the host's immune system.Such models have the potential to provide a more detailed and complete description of the pathogenesis of diseases within-host and identify other influencing factors that may not be detected otherwise. Mathematical models can be used to aid understanding of the global antibiotic resistance (ABR) crisis and identify new ways of combating this threat.ABR occurs when bacteria respond to random or selective pressures and adapt to new environments through the acquisition of new genetic traits. This is usually through the acquisition of a piece of DNA from other bacteria, a process called horizontal gene transfer (HGT), the modification of a piece of DNA within a bacterium, or through. Bacteria have evolved mechanisms that enable them to respond to environmental threats by mutation, and horizontal gene transfer (HGT): conjugation; transduction; and transformation. A frequent mechanism of HGT responsible for spreading antibiotic resistance on the global scale is conjugation, as it allows the direct transfer of mobile genetic elements (MGEs). Although there are several MGEs, the most important MGEs which promote the development and rapid spread of antimicrobial resistance genes in bacterial populations are plasmids and transposons. Each of the resistance-spread-mechanisms mentioned above can be modeled allowing us to understand the process better and to define strategies to reduce resistance.


Sujet(s)
Bactéries , Transfert horizontal de gène , Bactéries/génétique , Bactéries/effets des médicaments et des substances chimiques , Humains , Résistance microbienne aux médicaments/génétique , Modèles théoriques , Résistance bactérienne aux médicaments/génétique , Antibactériens/pharmacologie , Interactions hôte-pathogène/génétique
15.
Methods Mol Biol ; 2833: 211-223, 2024.
Article de Anglais | MEDLINE | ID: mdl-38949713

RÉSUMÉ

Genomic sequencing has revolutionized microbial typing methods and transformed high-throughput methods in reference, clinical, and research laboratories. The detection of antimicrobial-resistant (AMR) determinants using genomic methods can provide valuable information on the emergence of resistance. Here we describe an approach to detecting AMR determinants using an open access and freely available platform which does not require bioinformatic expertise.


Sujet(s)
Biologie informatique , Résistance bactérienne aux médicaments , Génome bactérien , Séquençage du génome entier , Séquençage du génome entier/méthodes , Résistance bactérienne aux médicaments/génétique , Biologie informatique/méthodes , Humains , Antibactériens/pharmacologie , Génomique/méthodes , Logiciel , Bactéries/génétique , Bactéries/effets des médicaments et des substances chimiques , Séquençage nucléotidique à haut débit/méthodes
16.
Methods Mol Biol ; 2833: 129-143, 2024.
Article de Anglais | MEDLINE | ID: mdl-38949707

RÉSUMÉ

Antibiotic resistance is a global challenge likely to cost trillions of dollars in excess costs in the health system and more importantly, millions of lives every year. A major driver of resistance is the absence of susceptibility testing at the time a healthcare worker needs to prescribe an antimicrobial. The effect is that many prescriptions are unintentionally wasted and expose mutable organisms to antibiotics increasing the risk of resistance emerging. Often simplistic solutions are applied to this growing issue, such as a naïve drive to increase the speed of drug susceptibility testing. This puts a spotlight on a technological solution and there is a multiplicity of such candidate DST tests in development. Yet, if we do not define the necessary information and the speed at which it needs to be available in the clinical decision-making progress as well as the necessary integration into clinical pathways, then little progress will be made. In this chapter, we place the technological challenge in a clinical and systems context. Further, we will review the landscape of some promising technologies that are emerging and attempt to place them in the clinic where they will have to succeed.


Sujet(s)
Antibactériens , Tests de sensibilité microbienne , Antibactériens/pharmacologie , Tests de sensibilité microbienne/méthodes , Humains , Résistance bactérienne aux médicaments/effets des médicaments et des substances chimiques , Bactéries/effets des médicaments et des substances chimiques
17.
Microb Biotechnol ; 17(7): e14510, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38970161

RÉSUMÉ

The Global Burden of Disease report of 2019 estimated 14 million infection-related deaths, making it the second leading cause of death after ischaemic heart disease. Bacterial pathogens accounted for 7.7 million deaths and deaths attributable to bacterial antibiotic resistance amounted to 1.3 million, describing a clear demand for novel antibiotics. Antibiotic development had its golden age in 1930-1960. Following failures in the screening of chemical libraries for novel antibiotics at the beginning of this century, the high cost of launching new antibiotics (estimated at US$ 1.4 billion per registered drug) and difficulties in achieving a return of investment for novel antibiotics, pharmaceutical industry has mostly left the field. The current Lilliput review analyses the question whether scientific or economic hurdles prevented the registration of new antibiotics. Scientifically, substantial progress has been achieved over recent years to define the chemical properties needed to overcome the permeation barrier in Gram-negative pathogens; in extending the chemical space of antibiotic candidates by full modular synthesis of suitable molecules; by extending bioprospecting to previously 'unculturable' bacteria or unusual bacteria; by attacking bacterial targets on the outer bacterial membrane; and by looking for support from structural biology, genomics, molecular genetics, phylogenetic analyses and deep machine learning approaches. However, these research activities were mostly conducted by academic researchers and biotech companies with limited financial resources. It thus seems that the development of new antibiotics, frequently described as the drying of the pipeline, is less limited by lack of scientific insight than by lack of the mobilization of the monetary resources needed to bring these discoveries to the market despite recent financial push and pull efforts of the public sector.


Sujet(s)
Antibactériens , Découverte de médicament , Antibactériens/pharmacologie , Humains , Résistance bactérienne aux médicaments , Bactéries/effets des médicaments et des substances chimiques , Bactéries/génétique , Bactéries/classification , Développement de médicament , Infections bactériennes/traitement médicamenteux , Infections bactériennes/microbiologie
18.
PLoS One ; 19(7): e0306693, 2024.
Article de Anglais | MEDLINE | ID: mdl-38976717

RÉSUMÉ

BACKGROUND: Endodontic treatment is one of the main dental treatments to manage inflamed or infected root canal systems of teeth. The success of endodontic treatment principally depends on eradicating microorganisms in the root canal by chemo-mechanical debridement with irrigation solutions like sodium hypochlorite (NaOCl). NaOCl has been used in concentrations ranging from 0.5% to 5.25%. This study determined the antimicrobial effectiveness of selected concentrations (0.5%, 1.0%, 2.6%, and 5.2%) of NaOCl in endodontic treatment. METHODS: The study sites were the University of Ghana Dental School (UGDS) and Noguchi Memorial Institute for Medical Research (NMIMR). Sixty infected single-rooted single-canal teeth were used. Before (S1) and after (S2), root canal samples during the endodontic treatment with the selected concentrations of NaOCl were examined via anaerobic and aerobic cultures. The isolates were identified using Matrix Assisted Laser Desorption Ionization-Time Of Flight Mass Spectrometry (MALDI-TOF MS). RESULTS: All S1 samples were positive for cultivable bacteria. Fifty-three (53) different microbial species belonging to 20 different microbial genera were isolated. Streptococcus viridans was the most frequently isolated microbe. There were zero isolates in the root canals irrigated with 2.6% and 5.2% NaOCl. Two teeth had isolates in the groups irrigated with the lower concentrations (0.5% and 1.0%) of NaOCl. The persistent bacteria were one species each of Streptococcus mitis and Streptococcus oralis, respectively. CONCLUSION: Root canal treatments using chemo-mechanical preparation with the selected concentrations (0.5%, 1.0%, 2.6%, and 5.2%) of NaOCl were effective in significantly reducing the microbial load, and for the 5.2% and 2.6% concentrations, in eliminating all the microorganisms.


Sujet(s)
Cavité pulpaire de la dent , Traitement de canal radiculaire , Hypochlorite de sodium , Hypochlorite de sodium/pharmacologie , Humains , Traitement de canal radiculaire/méthodes , Cavité pulpaire de la dent/microbiologie , Cavité pulpaire de la dent/effets des médicaments et des substances chimiques , Liquides d'irrigation endocanalaire/usage thérapeutique , Liquides d'irrigation endocanalaire/pharmacologie , Mâle , Adulte , Femelle , Résultat thérapeutique , Bactéries/effets des médicaments et des substances chimiques , Bactéries/isolement et purification , Adulte d'âge moyen
19.
PLoS One ; 19(7): e0306634, 2024.
Article de Anglais | MEDLINE | ID: mdl-38976712

RÉSUMÉ

In rearing systems for the Japanese eel Anguilla japonica, although it is assumed that microorganisms influence larval survival and mortality, particularly during the early stages of growth, the effects of bacterial communities on larval survival have yet to be sufficiently determined. In this study, we compared the bacterial communities associated with larval survival at three stages of eel growth. To artificially alter bacterial communities and assess larval survival, eel larvae were treated with 11 types of antibiotic, and larval survival and bacterial characteristics were compared between the antibiotic-treated and antibiotic-free control groups. Throughout the three growth stages, eels treated with four antibiotics (polymyxin B, tetracycline, novobiocin, and erythromycin) had survival rates higher than those in the control groups. The bacterial communities of surviving larvae in the control and antibiotic groups and dead larvae in the control groups were subsequently analyzed using 16S rRNA gene amplicon sequencing. PERMANOVA analysis indicated that these three larval groups were characterized by significantly different bacterial communities. We identified 14 biomarker amplicon sequence variants (ASVs) of bacterial genera such as Oceanobacter, Alcanivorax, Marinobacter, Roseibium, and Sneathiella that were enriched in surviving larvae in the antibiotic treatment groups. In contrast, all four biomarker ASVs enriched in dead larvae of the control groups were from bacteria in the genus Vibrio. Moreover, 52 bacterial strains corresponding to nine biomarkers were isolated using a culture method. To the best of our knowledge, this is the first study to evaluate the bacterial communities associated with the survival and mortality of larvae in during the early stages of Japanese eel growth and to isolate biomarker bacterial strains. These findings will provide valuable insights for enhancing larval survival in the eel larval rearing systems from a microbiological perspective.


Sujet(s)
Anguilla , Antibactériens , Marqueurs biologiques , Larve , Animaux , Larve/microbiologie , Larve/effets des médicaments et des substances chimiques , Larve/croissance et développement , Anguilla/microbiologie , Anguilla/croissance et développement , Antibactériens/pharmacologie , ARN ribosomique 16S/génétique , Bactéries/génétique , Bactéries/effets des médicaments et des substances chimiques , Bactéries/classification , Bactéries/isolement et purification , Bactéries/croissance et développement
20.
Arch Microbiol ; 206(8): 347, 2024 Jul 10.
Article de Anglais | MEDLINE | ID: mdl-38985339

RÉSUMÉ

Essential oils are among the most well-known phyto-compounds, and since ancient times, they have been utilized in medicine. Over 100 essential oils have been identified and utilized as therapies for various skin infections and related ailments. While numerous commercial medicines are available in different dosage forms to treat skin diseases, the persisting issues include their side effects, toxicity, and low efficacy. As a result, researchers are seeking novel classes of compounds as substitutes for synthetic drugs, aiming for minimal side effects, no toxicity, and high efficacy. Essential oils have shown promising antimicrobial activity against skin-associated pathogens. This review presents essential knowledge and scientific information regarding essential oil's antimicrobial capabilities against microorganisms that cause skin infections. Essential oils mechanisms against different pathogens have also been explored. Many essential oils exhibit promising activity against various microbes, which has been qualitatively assessed using the agar disc diffusion experiment, followed by determining the minimum inhibitory concentration for quantitative evaluation. It has been observed that Staphylococcus aureus and Candida albicans have been extensively researched in the context of skin-related infections and their antimicrobial activity, including established modes of action. In contrast, other skin pathogens such as Staphylococcus epidermidis, Streptococcus pyogens, Propionibacterium acnes, and Malassezia furfur have received less attention or neglected. This review report provides an updated understanding of the mechanisms of action of various essential oils with antimicrobial properties. This review explores the anti-infectious activity and mode of action of essential against distinct skin pathogens. Such knowledge can be valuable in treating skin infections and related ailments.


Sujet(s)
Huile essentielle , Huile essentielle/pharmacologie , Humains , Peau/microbiologie , Peau/effets des médicaments et des substances chimiques , Tests de sensibilité microbienne , Anti-infectieux/pharmacologie , Bactéries/effets des médicaments et des substances chimiques , Staphylococcus aureus/effets des médicaments et des substances chimiques , Candida albicans/effets des médicaments et des substances chimiques , Antibactériens/pharmacologie
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