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1.
J Clin Invest ; 132(18)2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36106638

RESUMO

BACKGROUNDSeveral molecular imaging strategies can identify bacterial infections in humans. PET affords the potential for sensitive infection detection deep within the body. Among PET-based approaches, antibiotic-based radiotracers, which often target key bacterial-specific enzymes, have considerable promise. One question for antibiotic radiotracers is whether antimicrobial resistance (AMR) reduces specific accumulation within bacteria, diminishing the predictive value of the diagnostic test.METHODSUsing a PET radiotracer based on the antibiotic trimethoprim (TMP), [11C]-TMP, we performed in vitro uptake studies in susceptible and drug-resistant bacterial strains and whole-genome sequencing (WGS) in selected strains to identify TMP resistance mechanisms. Next, we queried the NCBI database of annotated bacterial genomes for WT and resistant dihydrofolate reductase (DHFR) genes. Finally, we initiated a first-in-human protocol of [11C]-TMP in patients infected with both TMP-sensitive and TMP-resistant organisms to demonstrate the clinical feasibility of the tool.RESULTSWe observed robust [11C]-TMP uptake in our panel of TMP-sensitive and -resistant bacteria, noting relatively variable and decreased uptake in a few strains of P. aeruginosa and E. coli. WGS showed that the vast majority of clinically relevant bacteria harbor a WT copy of DHFR, targetable by [11C]-TMP, and that despite the AMR, these strains should be "imageable." Clinical imaging of patients with [11C]-TMP demonstrated focal radiotracer uptake in areas of infectious lesions.CONCLUSIONThis work highlights an approach to imaging bacterial infection in patients, which could affect our understanding of bacterial pathogenesis as well as our ability to better diagnose infections and monitor response to therapy.TRIAL REGISTRATIONClinicalTrials.gov NCT03424525.FUNDINGInstitute for Translational Medicine and Therapeutics, Burroughs Wellcome Fund, NIH Office of the Director Early Independence Award (DP5-OD26386), and University of Pennsylvania NIH T32 Radiology Research Training Grant (5T32EB004311-12).


Assuntos
Infecções Bacterianas , Trimetoprima , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias , Infecções Bacterianas/diagnóstico por imagem , Infecções Bacterianas/tratamento farmacológico , Radioisótopos de Carbono , Escherichia coli , Humanos , Trimetoprima/farmacologia , Trimetoprima/uso terapêutico
2.
Ann Med ; 54(1): 2500-2510, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36120867

RESUMO

Objective: To determine the minimum inhibitory concentration (MIC) distribution of antibacterial drugs and the susceptibility of non-tuberculous mycobacterial (NTM) isolates to provide a reference basis for the clinical selection of an effective starting regimen.Methods: The common clinical isolates of NTM in the respiratory tract, which met the standards of the American Thoracic Society for NTM lung disease, were collected. The MICs of 81 isolates were determined using the microbroth dilution method (Thermo Fisher Scientific, USA), as recommended by the Clinical and Laboratory Standards Institute, USA.Results: Included were 43 Mycobacterium avium complex (MAC) strains, 24 M. abscessus complex (MAB) strains, and 14 M. kansasii strains. The sensitivity rates of MAC to clarithromycin and amikacin were 81.4% and 79.1%, respectively, while the sensitivity rates to linezolid and moxifloxacin were only 20.9% and 9.3%; the MIC of rifabutin was the lowest (MIC50% was just 2 µg/mL). After incubation for 3-5 days, the sensitivity rate of MAB to clarithromycin was 87.5%; this decreased to 50% after 14 days' incubation. Most of them were susceptible to amikacin (91.6%), and most were resistant to moxifloxacin (95.8%), ciprofloxacin (95.8%), imipenem (95.8%), amoxicillin/clavulanate (95.8%), tobramycin (79.1%), doxycycline (95.8%) and trimethoprim/sulfamethoxazole (95.8%). intermediate (83.3%) and resistant (16.7%) to cefoxitin. The susceptibility to linezolid was only 33.3%. The sensitivity and resistance breakpoints of tigecycline were set to ≤0.5 and ≥8 µg/mL, respectively, and the sensitivity and resistance rates were 50% and 0%, respectively. M. kansasii was susceptible to clarithromycin, amikacin, linezolid, moxifloxacin, rifampicin and rifabutin (100%).Discussion: In Wenzhou, clarithromycin, amikacin and rifabutin have good antibacterial activity against MAC, while linezolid and moxifloxacin have high resistance. Amikacin and tigecycline have strong antibacterial activity against MAB, while most other antibacterial drugs are resistant to varying degrees. Most antibacterial drugs are susceptible to M. kansasii and have good antibacterial activity.Conclusion: The identification of NTM species and the detection of their MICs have certain guiding values for the treatment of NTM lung disease.Key MessageThe three most common respiratory non-tuberculous mycobacterial (NTM) isolates with clinical significance in the Wenzhou area were tested for drug susceptibility. The broth microdilution method was used to determine the minimum inhibitory concentration distribution of antibacterial drugs and the susceptibility of NTM isolates to provide a reference basis for the clinical selection of an effective starting regimen.


Assuntos
Pneumopatias , Infecções por Mycobacterium não Tuberculosas , Amicacina/farmacologia , Amicacina/uso terapêutico , Amoxicilina , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Cefoxitina/farmacologia , Cefoxitina/uso terapêutico , Ciprofloxacina/farmacologia , Ciprofloxacina/uso terapêutico , Claritromicina/farmacologia , Ácido Clavulânico/farmacologia , Ácido Clavulânico/uso terapêutico , Doxiciclina/farmacologia , Doxiciclina/uso terapêutico , Humanos , Imipenem/farmacologia , Imipenem/uso terapêutico , Linezolida/farmacologia , Linezolida/uso terapêutico , Testes de Sensibilidade Microbiana , Moxifloxacina/farmacologia , Moxifloxacina/uso terapêutico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Micobactérias não Tuberculosas , Sistema Respiratório , Rifabutina/farmacologia , Rifabutina/uso terapêutico , Rifampina/farmacologia , Rifampina/uso terapêutico , Sulfametoxazol/farmacologia , Sulfametoxazol/uso terapêutico , Tigeciclina/farmacologia , Tigeciclina/uso terapêutico , Tobramicina/farmacologia , Tobramicina/uso terapêutico , Trimetoprima/farmacologia , Trimetoprima/uso terapêutico
3.
J Enzyme Inhib Med Chem ; 37(1): 2621-2634, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36165032

RESUMO

A safer treatment for toxoplasmosis would be achieved by improving the selectivity profile of novel chemotherapeutics compared to the standard therapy pyrimethamine (PYR) and sulfadiazine (SDZ). We previously reported on the identification of the compounds with imidazole-thiosemicarbazide scaffold as potent and selective anti-Toxoplasma gondii (T. gondii) agents. In our current research, we report on the optimisation of this chemical scaffold leading to the discovery cyclic analogue 20 b with s-triazole core structure. This compound displayed prominent CC30 to IC50 selectivity index (SI) of 70.72, making it 160-fold more selective than SDZ, 11-fold more selective than PYR, and 4-fold more selective than trimethoprim (TRI). Additionally, this compound possesses prerequisite drug-like anti-Toxoplasma properties to advance into preclinical development; it showed ability to cross the BBB, did not induce genotoxic and haemolytic changes in human cells, and as well as it was characterised by low cellular toxicity.


Assuntos
Antiprotozoários , Toxoplasma , Antiprotozoários/farmacologia , Humanos , Imidazóis , Pirimetamina/farmacologia , Sulfadiazina/farmacologia , Sulfadiazina/uso terapêutico , Triazóis/farmacologia , Trimetoprima
4.
ACS Sens ; 7(9): 2691-2700, 2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36084142

RESUMO

Engineered protein switches have been widely applied in cell-based protein sensors and point-of-care diagnosis for the rapid and simple analysis of a wide variety of proteins, metabolites, nucleic acids, and enzymatic activities. Currently, these protein switches are based on two main types of switching mechanisms to transduce the target binding event to a quantitative signal, through a change in the optical properties of fluorescent molecules and the activation of enzymatic activities. In this paper, we introduce a new affinity-tunable protein switch strategy in which the binding of a small-molecule target with the protein activates the streptavidin-biotin interaction to generate a readout signal. In the absence of a target, the biotinylated protein switch forms a closed conformation where the biotin is positioned in close proximity to the protein, imposing a large steric hindrance to prevent the effective binding with streptavidin. In the presence of the target molecule, this steric hindrance is removed, thereby exposing the biotin for streptavidin binding to produce strong fluorescent signals. With this modular sensing concept, various sulfonamide, methotrexate, and trimethoprim drugs can be selectively detected on the cell surface of native and genetically engineered cells using different fluorescent dyes and detection techniques.


Assuntos
Biotina , Ácidos Nucleicos , Biotina/química , Corantes Fluorescentes , Metotrexato , Proteínas , Estreptavidina/análise , Sulfonamidas , Trimetoprima
5.
Mol Syst Biol ; 18(9): e10490, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36124745

RESUMO

Dose-response relationships are a general concept for quantitatively describing biological systems across multiple scales, from the molecular to the whole-cell level. A clinically relevant example is the bacterial growth response to antibiotics, which is routinely characterized by dose-response curves. The shape of the dose-response curve varies drastically between antibiotics and plays a key role in treatment, drug interactions, and resistance evolution. However, the mechanisms shaping the dose-response curve remain largely unclear. Here, we show in Escherichia coli that the distinctively shallow dose-response curve of the antibiotic trimethoprim is caused by a negative growth-mediated feedback loop: Trimethoprim slows growth, which in turn weakens the effect of this antibiotic. At the molecular level, this feedback is caused by the upregulation of the drug target dihydrofolate reductase (FolA/DHFR). We show that this upregulation is not a specific response to trimethoprim but follows a universal trend line that depends primarily on the growth rate, irrespective of its cause. Rewiring the feedback loop alters the dose-response curve in a predictable manner, which we corroborate using a mathematical model of cellular resource allocation and growth. Our results indicate that growth-mediated feedback loops may shape drug responses more generally and could be exploited to design evolutionary traps that enable selection against drug resistance.


Assuntos
Antibacterianos , Tetra-Hidrofolato Desidrogenase , Antibacterianos/farmacologia , Escherichia coli/genética , Retroalimentação , Tetra-Hidrofolato Desidrogenase/genética , Tetra-Hidrofolato Desidrogenase/farmacologia , Trimetoprima/farmacologia
6.
Waste Manag ; 152: 1-5, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35963201

RESUMO

Manure is a major source of antimicrobial-resistant bacteria and resistance genes carried by mobile genetic elements such as plasmids. In France, the number of on-farm biogas plants has increased significantly in recent years. Our study investigated the impact of mesophilic anaerobic digestion (AD) and the post-treatment of digestates on the fate of conjugative plasmids, along with their potential transfer of antimicrobial resistance. Samples of raw manure, digestates and post-treated digestates were collected from three on-farm biogas plants. Conjugative plasmids were captured using the Escherichia coli CV601 recipient strain and media supplemented with rifampicin and kanamycin - to which the recipient strain is resistant - and tetracycline, sulfamethoxazole, gentamicin, trimethoprim, amoxicillin, cefotaxime, ciprofloxacin or colistin. Putative transconjugants were identified and characterised by disc diffusion and whole genome sequencing. The results showed that the antimicrobial resistance genes transferred from the different matrices conferred resistance to tetracyclines, sulphonamides, trimethoprim, and/or streptomycin. Transconjugants were obtained from raw manure samples but not from digestates or post-digestates, suggesting that mesophilic AD processes may produce fewer conjugative plasmids potentially able to be transferred to Enterobacterales.


Assuntos
Antibacterianos , Esterco , Anaerobiose , Antibacterianos/farmacologia , Biocombustíveis , Farmacorresistência Bacteriana/genética , Escherichia coli/genética , Esterco/microbiologia , Plasmídeos/genética , Trimetoprima
7.
Microb Pathog ; 171: 105733, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36002114

RESUMO

Methicillin-resistant staphylococci have become leading cause of infectious diseases in humans and animals, being categorized as high priority pathogens by the World Health Organization. Although methicillin-resistant Staphylococcus sciuri (recently moved to Mammaliicoccus sciuri) has been widely reported in companion animals, there is scarce information regarding their clinical impact and genomic features. Herein, we reported the occurrence and genomic characteristics of methicillin-resistant M. sciuri recovered from fatal infections in pets admitted to an intensive care unit of a veterinary hospital, in Brazil. Two M. sciuri strains were isolated from bronchoalveolar lavage samples collected from dog (strain SS01) and cat (strain SS02) presenting with sepsis and acute respiratory distress syndrome. Both isolates displayed a multidrug-resistant profile, whereas whole-genome sequencing analysis confirmed the presence of the mecA gene, along to genetic determinant conferring resistance to macrolides, streptogramins, aminoglycosides, and trimethoprim. For both strains, the mec and crr gene complex shared high identity (≥97%) with analogue sequences from a M. sciuri isolated from a human wound infection, in the Czech Republic. Strains were assigned to the sequence type ST52 and the novel ST74. Phylogenomic analysis revealed a broad host range association of these strains with several hosts and sources, including humans, animals, food, and the environment through different years and geographic locations. Our findings demonstrate that infections caused by mecA-positive M. sciuri strains can be a serious threat for veterinary intensive care patients and the medical staff, with additional implications for One Health approaches.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Aminoglicosídeos , Animais , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Cães , Genômica , Humanos , Unidades de Terapia Intensiva , Macrolídeos , Resistência a Meticilina , Staphylococcus aureus Resistente à Meticilina/genética , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/veterinária , Staphylococcus , Estreptograminas , Trimetoprima
8.
Microb Drug Resist ; 28(9): 948-955, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35972354

RESUMO

Flavobacterium columnare, the causative agent of columnaris disease in a large variety of freshwater fish, is a major problem in commercial aquaculture. A limited number of antimicrobial therapies are available to control this disease; therefore, these agents must be used judiciously. To facilitate effective monitoring for changes in susceptibility, the Clinical Laboratory Standards Institute (CLSI) has a standard broth microdilution test method specific for F. columnare. However, there are no CLSI-approved criteria (termed epidemiological cutoff values [ECVs]) to interpret results. Nevertheless, researchers have developed provisional ECVs based on testing by one laboratory. To satisfy CLSI data requirements, three laboratories used the standard method to generate additional antimicrobial susceptibility data against ampicillin, enrofloxacin, erythromycin, florfenicol, flumequine, gentamicin, oxolinic acid, oxytetracycline, sulfadimethoxine/ormetoprim, and sulfamethoxazole-trimethoprim using 109 F. columnare isolates. The new data combined with previously published data from 120 F. columnare isolates were analyzed and ECVs proposed to CLSI. Of the 10 antimicrobials, ECVs were approved for ampicillin, enrofloxacin, erythromycin, florfenicol, flumequine, oxolinic acid, and oxytetracycline, which were published in the 2020 edition of the CLSI document VET04 performance standards. These ECVs will help microbiologists categorize decreased antimicrobial susceptibility among F. columnare and will help in surveillance efforts to ensure judicious antimicrobial use.


Assuntos
Anti-Infecciosos , Oxitetraciclina , Ampicilina , Animais , Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Enrofloxacina , Eritromicina , Peixes , Flavobacterium , Gentamicinas , Ácido Oxolínico , Sulfadimetoxina , Sulfametoxazol , Tianfenicol/análogos & derivados , Trimetoprima
9.
Chemosphere ; 307(Pt 2): 135760, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35931265

RESUMO

This experimental research proposes an environment-friendly and low-cost porous geopolymer composite membrane (PGCM) to treat antibiotics in hospital wastewater. The proposed PGCM consisted of two layers: a porous support layer and a dense coating layer. The dense coating layer was synthesized by incorporating variable TiO2 content (0, 2, 6, and 10 wt%) into the geopolymer matrix. The dense coating layer was of hierarchical mesoporous structure with 700 µm in thickness and adhered to the porous support layer. The average pore size, total pore volume, and open porosity of the dense coating layer decreased with an increase in TiO2, resulting in reduced water permeability. The PGCM was applied to remove six target antibiotics including amoxicillin, ciprofloxacin, norfloxacin, sulfamethoxazole, tetracycline, and trimethoprim in real hospital wastewater. By comparison, the PGCM with 10 wt% TiO2 achieved the highest antibiotic removal efficiencies, with the adsorption and combined adsorption/photodegradation removal efficiencies for the target antibiotics of 38-75% and 74-86%, respectively. The novelty of this research lies in the use of a tailor-made porous geopolymer composite membrane incorporated with TiO2 photooxidation as a single-step treatment of recalcitrant antibiotics contained in hospital wastewater.


Assuntos
Antibacterianos , Águas Residuárias , Adsorção , Amoxicilina , Ciprofloxacina , Hospitais , Norfloxacino , Porosidade , Sulfametoxazol , Tetraciclina , Titânio/química , Trimetoprima , Águas Residuárias/química , Água
10.
Artigo em Inglês | MEDLINE | ID: mdl-35886277

RESUMO

The current research focuses on the adsorption/desorption characteristics of the antibiotics ciprofloxacin (CIP) and trimethoprim (TRI) taking place in 17 agricultural soils, which are studied by means of batch-type experiments. The results show that adsorption was higher for CIP, with Freundlich KF values ranging between 1150 and 5086 Ln µmol1-n kg-1, while they were between 29 and 110 Ln µmol1-n kg-1 in the case of TRI. Other parameters, such as the Langmuir maximum adsorption capacity (qm(ads)), as well as the Kd parameter in the linear model and also the adsorption percentages, follow the same trend as KF. Desorption was lower for CIP (with KF(des) values in the range 1089-6234 Ln µmol1-n kg-1) than for TRI (with KF(des) ranging between 26 and 138 Ln µmol1-n kg-1). The higher irreversibility of CIP adsorption was also confirmed by its lower nF(des)/nF(ads) ratios, compared to TRI. Regarding soil characteristics, it was evidenced that nitrogen and carbon contents, as well as mineral fractions, had the highest influence on the adsorption/desorption process. These results can be considered relevant as regards the fate of both antibiotics when they reach the environment as pollutants and therefore could be considered in assessment procedures focused on environmental and public health aspects.


Assuntos
Poluentes do Solo , Solo , Adsorção , Antibacterianos , Ciprofloxacina , Poluentes do Solo/análise , Trimetoprima
11.
Cell Chem Biol ; 29(9): 1446-1464.e10, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-35835118

RESUMO

Chemogenetic methods enabling the rapid translocation of specific proteins to the plasma membrane (PM) in a single protein-single ligand manner are useful tools in cell biology. We recently developed a technique, in which proteins fused to an Escherichia coli dihydrofolate reductase (eDHFR) variant carrying N-terminal hexalysine residues are recruited from the cytoplasm to the PM using the synthetic myristoyl-d-Cys-tethered trimethoprim (mDcTMP) ligand. However, this system achieved PM-specific translocation only when the eDHFR tag was fused to the N terminus of proteins, thereby limiting its application. In this report, we engineered a universal PM-targeting tag for mDcTMP-induced protein translocation by grafting the hexalysine motif into an intra-loop region of eDHFR. We demonstrate the broad applicability of the new loop-engineered eDHFR tag and mDcTMP pair for conditional PM recruitment and activation of various tag-fused signaling proteins with different fusion configurations and for reversibly and repeatedly controlling protein localization to generate synthetic signal oscillations.


Assuntos
Tetra-Hidrofolato Desidrogenase , Trimetoprima , Membrana Celular/metabolismo , Escherichia coli/metabolismo , Ligantes , Proteínas , Transdução de Sinais , Tetra-Hidrofolato Desidrogenase/metabolismo , Trimetoprima/farmacologia
12.
Sci Total Environ ; 848: 157652, 2022 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-35905960

RESUMO

Water commuting is a major urban transportation method in Thailand. However, urban boat commuters risk exposure to microbially contaminated bioaerosols or splash. We aimed to investigate the microbial community structures, identify bacterial and viral pathogens, and assess the abundance of antimicrobial resistance genes (ARGs) using next-generation sequencing (NGS) at 10 sampling sites along an 18 km transportation boat route in the Saen Saep Canal, which traverses cultural, commercial, and suburban land-based zones. The shotgun metagenomic (Illumina HiSeq) and 16S rRNA gene amplicon (V4 region) (Illumina MiSeq) sequencing platforms revealed diverse microbial clusters aligned with the zones, with explicit segregation between the cultural and suburban sites. The shotgun metagenomic sequencing further identified bacterial and viral pathogens, and ARGs. The predominant bacterial pathogens (>0.5 % relative abundance) were the Burkholderia cepacia complex, Arcobacter butzleri, Burkholderia vietnamiensis, Klebsiella pneumoniae, and the Enterobacter cloacae complex. The viruses (0.28 %-0.67 % abundance in all microbial sequences) comprised mainly vertebrate viruses and bacteriophages, with encephalomyocarditis virus (33.3 %-58.2 % abundance in viral sequences), hepatitis C virus genotype 1, human alphaherpesvirus 1, and human betaherpesvirus 6A among the human viral pathogens. The 15 ARG types contained 611 ARG subtypes, including those resistant to beta-lactam, which was the most diverse and abundant group (206 subtypes; 17.0 %-27.5 %), aminoglycoside (94 subtypes; 9.6 %-15.3 %), tetracycline (80 subtypes; 15.6 %-20.2 %), and macrolide (79 subtypes; 14.5 %-32.1 %). Interestingly, the abundance of ARGs associated with resistance to beta-lactam, trimethoprim, and sulphonamide, as well as A. butzleri and crAssphage, at the cultural sites was significantly different from the other sites (p < 0.05). We demonstrated the benefits of using NGS to deliver insights into microbial communities, and antimicrobial resistance, both of which pose a risk to human health. Using NGS may facilitate microbial risk mitigation and management for urban water commuters and proximal residents.


Assuntos
Antibacterianos , Bacteriófagos , Aminoglicosídeos , Antibacterianos/farmacologia , Bactérias , Bacteriófagos/genética , Farmacorresistência Bacteriana/genética , Humanos , Macrolídeos , Metagenômica , RNA Ribossômico 16S/genética , Sulfonamidas , Tetraciclina , Meios de Transporte , Trimetoprima , Água , beta-Lactamas
13.
Environ Res ; 214(Pt 2): 113916, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35872321

RESUMO

The presence of emerging pollutants, and specifically antibiotics, in agricultural soils has increased notably in recent decades, causing growing concern as regards potential environmental and health issues. With this in mind, the current study focuses on evaluating the toxicity exerted by three antibiotics (amoxicillin, trimethoprim, and ciprofloxacin) on the growth of soil bacterial communities, when these pollutants are present at different doses, and considered in the short, medium, and long terms (1, 8 and 42 days of incubation). Specifically, the research was carried out in 12 agricultural soils having different physicochemical characteristics and was performed by means of the leucine (3H) incorporation method. In addition, changes in the structure of soil microbial communities at 8 and 42 days were studied in four of these soils, using the phospholipids of fatty acids method for this. The main results indicate that the most toxic antibiotic was amoxicillin, followed by trimethoprim and ciprofloxacin. The results also show that the toxicity of amoxicillin decreases with time, with values of Log IC50 ranging from 0.07 ± 0.05 to 3.43 ± 0.08 for day 1, from 0.95 ± 0.07 to 3.97 ± 0.15 for day 8, and from 2.05 ± 0.03 to 3.18 ± 0.04 for day 42, during the incubation period. Regarding trimethoprim, 3 different behaviors were observed: for some soils the growth of soil bacterial communities was not affected, for a second group of soils trimethoprim toxicity showed dose-response effects that remained persistent over time, and, finally, for a third group of soils the toxicity of trimethoprim increased over time, being greater for longer incubation times (42 days). As regards ciprofloxacin, this antibiotic did not show a toxicity effect on the growth of soil bacterial communities for any of the soils or incubation times studied. Furthermore, the principal component analysis performed with the phospholipids of fatty acids results demonstrated that the microbial community structure of these agricultural soils, which persisted after 42 days of incubation, depended mainly on soil characteristics and, to a lesser extent, on the dose and type of antibiotic (amoxicillin, trimethoprim or ciprofloxacin). In addition, it was found that, in this research, the application of the three antibiotics to soils usually favored the presence of fungi and Gram-positive bacteria.


Assuntos
Poluentes Ambientais , Poluentes do Solo , Amoxicilina/análise , Amoxicilina/metabolismo , Amoxicilina/toxicidade , Antibacterianos/toxicidade , Bactérias , Ciprofloxacina/metabolismo , Ciprofloxacina/toxicidade , Poluentes Ambientais/análise , Ácidos Graxos/metabolismo , Fosfolipídeos/análise , Fosfolipídeos/metabolismo , Fosfolipídeos/farmacologia , Solo/química , Microbiologia do Solo , Poluentes do Solo/análise , Trimetoprima/análise , Trimetoprima/metabolismo , Trimetoprima/toxicidade
14.
Artigo em Inglês | MEDLINE | ID: mdl-35880470

RESUMO

There is currently a dearth of information on the determination, occurrence and ecotoxicological risk of antibiotics in dumpsite leachates and hospital wastewater in Africa. A quick, easy, cheap, effective, rugged and safe (QuEChERS) protocol which combines extraction and clean-up in one step was optimized for the determination of antibiotics sulfadoxine, sulfamethazine and trimethoprim in dumpsite leachates and hospital wastewater. The occurrence and ecotoxicological risk of target antibiotics were investigated in wastewater from two hospitals, effluent receiving water and leachates from three dumpsites in Ibadan, Nigeria. Recoveries in hospital wastewater ranged from 53 to 116% while recoveries ranged from 50 to 89% in leachates. Method limits of quantification ranged from 0.7 to 12.1 µg L-1 in hospital wastewater and from 6.2 to 38.8 µg L-1 in leachates. Intra-day precisions (% RSD) were ≤ 21%. High concentrations of target antibiotics were measured: up to 475 µg L-1 for sulfamethazine in leachates, 118 µg L-1 for trimethoprim in hospital wastewater and 117 µg L-1 for sulfadoxine in effluent receiving water. Sulfadoxine presented high risk to algae, daphnid and fish in hospital wastewater, effluent receiving water and leachates. This work highlights the need for adequate and sound management of wastes containing pharmaceuticals in Nigeria.


Assuntos
Águas Residuárias , Poluentes Químicos da Água , Animais , Antibacterianos/análise , Hospitais , Nigéria , Sulfadoxina , Sulfametazina , Trimetoprima , Águas Residuárias/análise , Água/análise , Poluentes Químicos da Água/análise
15.
Cell Mol Biol (Noisy-le-grand) ; 68(2): 203-207, 2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-35869729

RESUMO

Streptococcus pneumoniae is a common cause of bacterial infections of the respiratory system, middle ear infection, bacteremia, meningitis, and pneumonia, especially in children. Due to the lack of information about the frequency and resistance of Streptococcus pneumoniae to antibiotics, the present study was performed to determine the frequency of carriers of Streptococcus pneumoniae and its microbial resistance in children. For this purpose, the current descriptive cross-sectional study was conducted from November to March 2020 on 554 children aged 2-12 years in kindergartens and schools. This study collected samples with a sterile swab from the nasopharyngeal region, transported them to the laboratory by a transport medium, and then cultured them on an agar culture medium. After isolation, confirmatory tests and antibiotic susceptibility were performed. The results were analyzed using SPSS16 software and interpreted according to Mann Whitney U and Chi-Square Tests. Streptococcus pneumoniaewas found in 15% of samples, and the antibiotic resistance of the isolates to the antibiotics azithromycin, amoxicillin, rifampicin, amoxicillin-clavulanic acid, trimethoprim/Sulfamethoxazole, and ceftriaxone were 63.9%, 56.6%, 41%, 37.3%, 37.3%, and 3.6%, respectively. Also, 31.1% of the isolates were not resistant to any antibiotics. According to the results, excessive use of antibiotics has led to high resistance to azithromycin, amoxicillin, amoxicillin/clavulanic acid, and trimethoprim/Sulfamethoxazole, which indicates an increased risk of refractory infectious diseases. For this reason, it is necessary to adequately educate physicians and the general public about the overuse of antibiotics.


Assuntos
Antibacterianos , Streptococcus pneumoniae , Amoxicilina , Combinação Amoxicilina e Clavulanato de Potássio , Antibacterianos/farmacologia , Azitromicina , Criança , Estudos Transversais , Humanos , Testes de Sensibilidade Microbiana , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/genética , Sulfametoxazol , Trimetoprima
16.
J Hazard Mater ; 437: 129369, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-35897182

RESUMO

Antibiotics in human urine could accelerate dissemination of antibiotics resistance genes (ARGs), posing potential threat to sewage. The nitritation of source-separated urine was a critical step to realize the urine resourcelization and nitrogen stabilization. However, the synergic control on antibiotics and ARGs during urine nitritation was unrevealed. This study investigated the removal profiles of five typical antibiotics and the shifts of microbial community and ARGs during stable nitritation. The result showed that sulfamethoxazole and roxithromycin were effectively eliminated with high removal efficiency of (95 ± 5) % and (90 ± 10) %, followed by enrofloxacin with removal efficiency of (60 ± 5) %, whereas trimethoprim and chloramphenicol showed low removal efficiency of less than 40 %. Ammonia oxidation bacteria and heterotrophic bacteria equally contributed to elimination of sulfamethoxazole with a high biodegradation rate of 0.1534 L/gVSS·h, while sorption and biodegradation jointly promoted other antibiotics removal. The total relative abundance of top 25 bacteria genera was decreased by 10 %. The total relative abundance of top 30 ARGs was decreased by more than 20 %, which was corresponding to the variation of bacterial community. The findings in this research would get a deeper insight into the eliminating antibiotics and controlling ARGs dissemination during nitritation of source-separated urine.


Assuntos
Antibacterianos , Esgotos , Antibacterianos/farmacologia , Bactérias/genética , Genes Bacterianos , Humanos , Esgotos/microbiologia , Sulfametoxazol , Trimetoprima , Águas Residuárias/microbiologia
17.
J Hazard Mater ; 438: 129396, 2022 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-35785739

RESUMO

The inactivation of antibiotic resistant bacteria (ARB) and genes (ARGs) in an advanced plant combining ozonation and granular activated carbon (GAC) filtration applied for effluent after conventional activated sludge treatment at a full-scale urban wastewater treatment plant was investigated for over 13 consecutive months. The nitrite compensated specific ozone dose ranged between 0.4 and 0.7 g O3/g DOC with short-time sampling campaigns (0.2-0.9 g O3/g DOC). Samples were analysed with culture-dependent methods for bacterial targets and with qPCR for genes. The log removal values were correlated with a decrease of the matrix UV absorption at 254 nm (ΔUV254) and indicated a range of ΔUV254 that corresponds to a sufficient membrane damage to affect DNA. For trimethoprim/sulfamethoxazole resistant E. coli, sul1, ermB and tetW, this phase was observed at ΔUV254 of ~30 % (~0.5 g O3/g DOC). For ampicillin resistant E. coli and blaTEM-1, it was observed around 35-40 % (~0.7 g O3/g DOC), which can be linked to mechanisms related to oxidative damages in bacteria resistant to bactericidal antibiotics. GAC treatment resulted in a further abatement for trimethoprim/sulfamethoxazole E. coli, sul1 and tetW, and in increase in absolute and relative abundance of ermB and blaTEM-1.


Assuntos
Ozônio , Purificação da Água , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Antibacterianos/farmacologia , Bactérias/genética , Carvão Vegetal/farmacologia , Resistência Microbiana a Medicamentos/genética , Escherichia coli/genética , Ozônio/análise , Projetos Piloto , Sulfametoxazol , Trimetoprima , Águas Residuárias/análise , Purificação da Água/métodos
18.
Aquat Toxicol ; 250: 106243, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35872527

RESUMO

The high consumption and subsequent input of antibacterial compounds in marine ecosystems has become a worldwide problem. Their continuous presence in these ecosystems allows a direct interaction with aquatic organisms and can cause negative effects over time. The objective of the present study was to evaluate the effects of exposure to three antibacterial compounds of high consumption and presence in marine ecosystems (Ciprofloxacin CIP, Sulfadiazine SULF and Trimethoprim TRIM) on the physiology of the gilthead sea bream, Sparus aurata. Plasma parameters, enzymatic biomarkers of oxidative stress and damage and expression of genes related to stress and growth were assessed in exposed S. aurata specimens. For this purpose, sea bream specimens were exposed to individual compounds at concentrations of 5.2 ± 2.1 µg L-1 for CIP, 3.8 ± 2.7 µg L-1 for SULF and 25.7 ± 10.8 µg L-1 for TRIM during 21 days. Exposure to CIP up-regulated transcription of genes associated with the hypothalamic-pituitary-thyroid (HPT) (thyrotropin-releasing hormone, trh) and hypothalamic-pituitary-interrenal (HPI) axes (corticotropin-releasing hormone-binding protein, crhbp) in the brain, as well as altering several hepatic stress biomarkers (catalase, CAT; glutathione reductase, GR; and lipid peroxidation, LPO). Similar alterations at the hepatic level were observed after exposure to TRIM. Overall, our study indicates that S. aurata is vulnerable to environmentally relevant concentrations of CIP and TRIM and that their exposure could lead to a stress situation, altering the activity of antioxidant defense mechanisms as well as the activity of HPT and HPI axes.


Assuntos
Perciformes , Dourada , Poluentes Químicos da Água , Animais , Antibacterianos/farmacologia , Biomarcadores/metabolismo , Ciprofloxacina/metabolismo , Ecossistema , Expressão Gênica , Glutationa Redutase/metabolismo , Perciformes/metabolismo , Dourada/metabolismo , Estresse Fisiológico , Sulfadiazina/metabolismo , Sulfadiazina/farmacologia , Trimetoprima/metabolismo , Trimetoprima/toxicidade , Poluentes Químicos da Água/toxicidade
19.
Angew Chem Int Ed Engl ; 61(36): e202207905, 2022 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-35816052

RESUMO

Self-labeling protein tags can introduce advanced molecular motifs to specific cellular proteins. Here we introduce the third-generation covalent TMP-tag (TMP-tag3) and showcase its comparison with HaloTag and SNAP-tag. TMP-tag3 is based on a proximity-induced covalent Michael addition between an engineered Cys of E. coli dihydrofolate reductase (eDHFR) and optimized trimethoprim (TMP)-acrylamide conjugates with minimal linkers. Compared to previous versions, the TMP-tag3 features an enhanced permeability when conjugated to fluorogenic spirocyclic rhodamines. As a small protein, the 18-kD eDHFR is advantageous in tagging selected mitochondrial proteins which are less compatible with bulkier HaloTag fusions. The proximal N-C termini of eDHFR also enable facile insertion into various protein loops. TMP-tag3, HaloTag, and SNAP-tag are orthogonal to each other, collectively forming a toolbox for multiplexed live-cell imaging of cellular proteins under fluorescence nanoscopy.


Assuntos
Escherichia coli , Trimetoprima , Corantes Fluorescentes , Proteínas , Rodaminas , Tetra-Hidrofolato Desidrogenase
20.
J Hazard Mater ; 435: 128943, 2022 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-35650718

RESUMO

Ultrafiltration (UF) was assessed at chemical, microbiological, genetical and toxicological level and in terms of removing specific antibiotic-related microcontaminants from urban wastewater. The UF capacity to remove various antibiotics (clarithromycin, erythromycin, ampicillin, ofloxacin, sulfamethoxazole, trimethoprim, and tetracycline; [A0] = 100 µg L-1) was optimised with respect to the feed recirculation rate (25-50%) and feed/transmembrane pressure (1.5-3/1.5-2.4 bar, respectively). Here, we tested the UF capacity to reduce the cultivable bacteria (faecal coliforms, total heterotrophs, Enterococci, Pseudomonas aeruginosa), enteric opportunistic pathogens, including antibiotic-resistant bacteria (ARB) and antibiotic-resistance genes (ARGs) load. Moreover, the toxicity towards Daphnia magna and three plant species was investigated. Upon optimisation of UF, the removal of antibiotics ranged from 19% for trimethoprim to 95% for clarithromycin. The concentration of cultivable faecal coliforms in the permeate was significantly reduced compared to the feed (P < 0.001), whereas all the bacterial species decreased by more than 3 logs. A similar pattern of reduction was observed for the ARGs (P < 0.001) and enteric opportunistic pathogens (~3-4 logs reduction). A nearly complete removal of the antibiotics was obtained by UF followed by granular activated carbon adsorption (contact time: 90 min), demonstrating the positive contribution of such combination to the abatement of chemical microcontaminants.


Assuntos
Antibacterianos , Águas Residuárias , Antagonistas de Receptores de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Antibacterianos/farmacologia , Bactérias/genética , Claritromicina , Trimetoprima , Ultrafiltração , Águas Residuárias/microbiologia
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