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1.
J Environ Sci (China) ; 148: 567-578, 2025 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-39095189

RESUMEN

Erythromycin fermentation residue (EFR) represents a typical hazardous waste produced by the microbial pharmaceutical industry. Although electrolysis is promising for EFR disposal, its microbial threats remain unclear. Herein, metagenomics was coupled with the random forest technique to decipher the antibiotic resistance patterns of electrochemically treated EFR. Results showed that 95.75% of erythromycin could be removed in 2 hr. Electrolysis temporarily influenced EFR microbiota, where the relative abundances of Proteobacteria and Actinobacteria increased, while those of Fusobacteria, Firmicutes, and Bacteroidetes decreased. A total of 505 antibiotic resistance gene (ARG) subtypes encoding resistance to 21 antibiotic types and 150 mobile genetic elements (MGEs), mainly including plasmid (72) and transposase (52) were assembled in EFR. Significant linear regression models were identified among microbial richness, ARG subtypes, and MGE numbers (r2=0.50-0.81, p< 0.001). Physicochemical factors of EFR (Total nitrogen, total organic carbon, protein, and humus) regulated ARG and MGE assembly (%IncMSE value = 5.14-14.85). The core ARG, MGE, and microbe sets (93.08%-99.85%) successfully explained 89.71%-92.92% of total ARG and MGE abundances. Specifically, gene aph(3')-I, transposase tnpA, and Mycolicibacterium were the primary drivers of the resistance dissemination system. This study also proposes efficient resistance mitigation measures, and provides recommendations for future management of antibiotic fermentation residue.


Asunto(s)
Eritromicina , Fermentación , Metagenómica , Antibacterianos/farmacología , Farmacorresistencia Microbiana/genética , Farmacorresistencia Bacteriana/genética
2.
Front Med (Lausanne) ; 11: 1440992, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39314225

RESUMEN

Introduction: Gastroparesis is a disorder characterized by impaired gastric emptying and the accumulation of food in the intestines without any clear mechanical cause. Gastroparesis in critical care patients is a prevalent issue in the intensive care unit. The disruption of normal gastrointestinal motility in critically ill patients is linked to a significant risk of intolerance to enteral feeding, colonization of the gastrointestinal tract with pathogenic bacterial strains, increased permeability of the intestinal wall, translocation of the intestinal microbiota, leading to progressive malnutrition, and potential development of bacterial infection. Materials and methods: The literature was reviewed to assess the benefits and risks associated with the use of this medication. Aim: The aim of the study was to treat the symptoms of gastroparesis and stimulate gastrointestinal motility. Consequently, the aim was to reduce the amount of backed-up food content in the stomach, accelerate gastrointestinal motility, and return to intestinal feeding. Results: Gastroparesis is a frequent issue among patients in the intensive care unit. Critical illness can lead to gastrointestinal motility disorders, causing slowed gastric emptying. This increases the risk of problems such as intolerance to enteral feeding, regurgitation, and aspiration of gastrointestinal contents into the respiratory tract, as well as colonization of the gastrointestinal tract by pathogens. Over time, impaired intestinal absorption can result in malnutrition, necessitating the initiation of parenteral nutrition. Conclusion: After analysis of the literature and published scientific reports, as well as considering their own research, it is evident that erythromycin, as a prokinetic drug, effectively enhances gastrointestinal motility. This contributes to stimulating gastric emptying in critically ill patients with gastroparesis who are hospitalized in an intensive care unit. The use of erythromycin in combination with metoclopramide and/or itopride hydrochloride allows for a synergistic effect, leading to the quickest possible return to enteral feeding.

3.
Heliyon ; 10(16): e35536, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39220992

RESUMEN

The study focused on the extraction of free erythromycin from commercially manufactured tablets and the use of metal salts to synthesize erythromycin-metal complexes, specifically involving silver (Ag), nickel (Ni), cobalt (Co), and copper (Cu). The synthesis was confirmed through various methods, including elemental analysis, thermogravimetric analysis, Fourier-transform infrared (FTIR), and UV-visible spectroscopy. The microbiological investigation involved Salmonella typhi, Escherichia coli, Staphylococcus aureus, Bacillus cereus, Candida albicans, and Microsporum canis as test organisms. The NCCLS broth microdilution reference method was used to determine the minimum fungicidal concentration and minimum inhibitory concentration of the complexes. The synthesized complexes were highly effective against a variety of fungi and bacteria, with compound Ery-Cu having MIC as low as 1.56 mg/mL, Ery-Cu and Ery-Ni with MBCs of 6.25 mg/mL and Ery-Cu having MFC of 6.25 mg/mL. Dose-dependent inhibitory effects were found upon examination of the antimicrobial susceptibility of specific complexes (Cu, Ni, Co and Ag) at varying concentrations of 100, 50, 25 and 12.5 mm/mL. Antibiotic susceptibility testing revealed efficacy against the tested pathogens. The study suggests that the synthesis of erythromycin-metal complexes, coupled with their antibacterial effectiveness against a diverse spectrum of bacteria and fungi, as they showed promising inhibitory properties when tested against a range of test species (Bacillus cereus, Staphylococcus aureus, Escherichia coli, Salmonella typhi, Candida albicans, and Microsporum canis), could lead to the development of innovative antibacterial agents. Molecular docking simulations were used to examine the interactions between metal complexes with proteins filamentous temperature-sensitive protein Z and lanosterol 14α-demethylase. The study highlights the need for further exploration in pharmaceutical research.

4.
Clin Cosmet Investig Dermatol ; 17: 1999-2007, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39247134

RESUMEN

Rosacea is a common dermatosis with multiple pathogeneses, among which, rosacea fulminans may serve as a rare but severe subtype. This inflammatory disease usually presents as abrupt multiple erythema, pustules, and nodules localized on the face. Pregnancy and related changes of hormone levels may play a key role in the development and progression of the disease, although the exact mechanisms are unknown. In particular, treatment options, which includes systemic glucocorticosteroids, isotretinoin, and partial oral antibiotics, may be limited in pregnancy. Owing to the limited number of reported cases, standard diagnosis, treatment, and management guidelines remain unclear. Here, we report a case of rosacea fulminans happening in pregnancy treated successfully with oral erythromycin and short-term glucocorticosteroids, and share our review of the characteristics of RF cases during pregnancy.

5.
Aquat Toxicol ; 275: 107070, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39217791

RESUMEN

Discharged sewage is the dominant source of urban river pollution. Macrolide antibiotics have emerged as prominent contaminants, which are frequently detected in sewage and rivers and pose a threat to aquatic microbial community. As a typical primary producer, periphyton is crucial for maintaining the biodiversity and functions of aquatic ecosystem. However, effects of antibiotic exposure time as well as the recovery process of periphyton remain undetermined. In the present study, five exposure scenarios of two typical macrolides, erythromycin (ERY) and roxithromycin (ROX) were investigated at 50 µg/L, dose to evaluate their potential detrimental effects on the structure and function of periphyton and the subsequent recovery process in 14 days. Results revealed that the composition of periphytic community returned to normal over the recovery period, except for a few sensitive species. The antibiotics-caused significant photodamage to photosystem II, leading to continuous inhibition of the photosynthetic capacity of periphyton. Furthermore, no significant difference in carbon metabolism capacity was observed after direct antibiotic exposure, while the amine carbon utilization capacity of periphyton remarkably increased during the recovery process. These results indicated that periphyton community was capable of coping with the periodic exposure of antibiotic pollutants and recovering on its own. However, the ecological functions of periphyton can be permanently disturbed due to macrolide exposure. Overall, this study sheds light on the influence of macrolide exposure on the development, structure and function of the periphytic microbial community in rivers.


Asunto(s)
Antibacterianos , Macrólidos , Perifiton , Ríos , Contaminantes Químicos del Agua , Ríos/química , Contaminantes Químicos del Agua/toxicidad , Antibacterianos/toxicidad , Macrólidos/toxicidad , Perifiton/efectos de los fármacos , Roxitromicina/toxicidad , Eritromicina/toxicidad , Fotosíntesis/efectos de los fármacos
6.
Respir Investig ; 62(6): 1079-1087, 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39326270

RESUMEN

BACKGROUND: Long-term macrolide therapy for non-cystic fibrosis bronchiectasis (NCFB) can play a significant role. However, such data are insufficient regarding the efficacy against severe exacerbation and adverse effects, including the emergence of macrolide-resistant pathogens and prolonged macrolide use beyond 1 year. METHODS: Randomized controlled trials (RCTs) and prospective observational studies comparing the efficacy and safety of macrolides and placebo in adult patients with NCFB were screened on April 10, 2024. The primary outcome was severe exacerbation frequency. RESULTS: Ten RCTs ≤1 year study durations were included. Most studies mainly included patients with a history of >2 exacerbations. Macrolides had a tendency to reduce the frequency of severe exacerbations compared with placebo (odds ratio = 0.54, 95% confidence interval (CI) = 0.25-1.18). Macrolides significantly reduced the frequency of exacerbations (rate ratio = 0.58, 95% CI = 0.48-0.69), prolonged the time to first exacerbation (rate ratio = 0.41, 95% CI = 0.30-0.55), improved the changes in SGRQ scores [mean difference (MD) = -3.99, 95% CI = -4.63-3.44] and percent predicted forced expiratory volume in 1 s (MD = -2.30, 95% CI = 0.26-4.33), and reduced sputum volume (gram) (MD = -7.44, 95% CI = -9.15-5.74). Additionally, macrolides did not increase drug-related adverse events leading to discontinuation. Qualitative SR of pathogens indicated macrolides might increase the number of macrolide-resistant oropharyngeal and sputum pathogens and the emergence of Pseudomonas aeruginosa. CONCLUSIONS: Our results support macrolide therapy for patients with NCFB. Studies with an observation period of >1 year or those focusing on patients with/without a minimal exacerbation history are required to determine the long-term effects on patients with NCFB.

7.
Artículo en Inglés | MEDLINE | ID: mdl-39313898

RESUMEN

INTRODUCTION: The macrolide-resistant Bordetella pertussis (MRBp) has appeared in Asia and has even been prevalent in China. Since the antibiotic sensitivity test is not carried out in the clinical setting, macrolide is still the first choice of antibiotic in MRBp infection. Further, the macrolide therapy for pertussis needs to be revised. Macrolide has always shown a positive effect on other macrolide-resistant bacterium infections in clinical applications. However, the mechanism of macrolide on MRBp remains unclear. OBJECTIVE: The objective of this study was to investigate the effect of virulence of MRBp under the sub-MIC erythromycin. METHODS: This study evaluated a representative isolate BP19147 (ptxP1/fhaB3-MRBp) under a series of sub-inhibitory concentrations of erythromycin. We measured the growth curve, biofilm formation, and autoaggregation assay under Stainer and Scholte (SS) broth. The relative gene expression was detected by RT-qPCR. RESULTS: The proteomics was detected by label-fee DIA. The growth ability and virulence factors of MR isolate BP19147 were inhibited by sub-MIC of erythromycin and had a concentration- dependent effect. From the proteomics results, the pertussis toxin, filamentous haemagglutinin, and pertactin did not show a statistical difference (p >0.05). Other virulence factors (including dermonecrotic toxin, Invasive Adenylate cyclase/haemolysin. etc) showed a statistical difference (p <0.05). In the KEGG enrichment, the BvgAS system, biofilm formation, and some adaptive systems were inhibited by erythromycin. CONCLUSION: The sub-MIC of erythromycin may reduce the virulence of MRBp, which will provide a theoretical basis for the rational use of erythromycin for MRBp infection and help the development of new antibiotics.

8.
Saudi Pharm J ; 32(9): 102152, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39165579

RESUMEN

Skin infections considered as one of the predominant disorders that could greatly influence humans. Topical drug delivery is believed to be an effective substitute to systemically delivered medication for skin disorders management. Erythromycin has been proven to retain anti-bacterial activity. Based on that, the aim of existent study is to develop a proper nanocarrier, namely; nanoemulsion using tea tree oil including Erythromycin. Applying quality by design approach, the optimized nanoemulsion was selected based on number of independent variables namely; particle size and in vitro release study. Yet, in order to get appropriate topical application, the optimized nanoemulsion was combined with previously prepared hydrogel base to provide Erythromycin based nanoemulgel. The developed nanoemulgel was assessed for its organoleptic and physical characters to ensure its suitability for topical application. Stability study was implemented over three months after being kept in two distinct environments. Eventually, the antibacterial behavior of the preparation was investigated on MRSA to verify the expected antibacterial improvement and validate the effectiveness of the developed nanocarrier. The formulation showed consistent appearance, with pH (6.11 ± 0.19), viscosity (10400 ± 1275 cP), spreadability (54.03 ± 2.3 mm), extrudability (80.36 ± 3.15 g/cm2) and drug content (99.3 ± 0.46 %) that seemed to be satisfied for topical application. It could provide 48.1 ± 4.2 % releases over 6 h in addition to be stable at room temperature and at refrigerator. Ultimately, the formula showed a significant antibacterial activity against MRSA proving the combination and the nanocarrier effectiveness.

9.
Food Chem ; 461: 140830, 2024 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-39151348

RESUMEN

Herein, we have manufactured a newly designed bifunctional impedimetric and amperometric immunosensor for rapidly detecting erythromycin (ERY) in complicated environments and food stuffs. For this, bimetallic cobalt/cerium-layered double hydroxide nanosheets (CoCe-LDH NSs), which was derived from Co-based zeolite imidazole framework via the structure conversion, was simultaneously utilized as the bioplatform for anchoring the ERY-targeted antibody and for modifying the gold and screen printed electrode. Basic characterizations revealed that CoCe-LDH NSs was composed of mixed metal valences, enrich redox, and abundant oxygen vacancies, facilitating the adhesion on the electrode, the antibody adsorption, and the electron transfers. The manufactured impedimetric and amperometric immunosensor based on CoCe-LDH has showed the comparable sensing performance, having a wide linear detection range from 1.0 fg mL-1 to 1.0 ng mL-1 with the ultralow detection limit toward ERY. Also, the portable, visualized, and efficient analysis of ERY was then attained at the smartphone-assisted CoCe-LDH-based SPE.


Asunto(s)
Técnicas Biosensibles , Cobalto , Técnicas Electroquímicas , Eritromicina , Hidróxidos , Teléfono Inteligente , Cobalto/química , Eritromicina/análisis , Hidróxidos/química , Técnicas Electroquímicas/instrumentación , Técnicas Electroquímicas/métodos , Inmunoensayo/instrumentación , Inmunoensayo/métodos , Técnicas Biosensibles/instrumentación , Límite de Detección , Electrodos , Contaminación de Alimentos/análisis , Antibacterianos/análisis
10.
J Clin Med ; 13(15)2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39124594

RESUMEN

Background/Objectives:Staphylococcus lugdunensis is a coagulase-negative staphylococcus (CoNS) commonly found on human skin. Unlike other CoNS, S. lugdunensis has a notable potential to cause severe infections comparable to Staphylococcus aureus. This study aimed to characterize the clinical and microbiological profile of patients with S. lugdunensis skin infections at a single center. Methods: We conducted a retrospective analysis of patient records from the Dermatology Department of the University Hospital of Heraklion, Greece, covering the period from January 2014 to January 2024. Patients' clinical presentations, demographics, infection sites, comorbidities, prior infections, antimicrobial treatments, and therapeutic responses were examined. Specimens were collected, transported, and processed according to standardized microbiological protocols. Bacterial identification and antibiotic susceptibility testing were performed using the Vitek 2 automated system and MALDI-TOF MS, with results interpreted according to Clinical and Laboratory Standards Institute (CLSI) criteria. Results: A total of 123 skin specimens positive for S. lugdunensis were analyzed. The cohort comprised 62 males (50.4%) and 61 females (49.6%), with a mean age of 40.24 ± 20.14 years. Most specimens were collected from pus (84%), primarily from below the waist (66.7%). Hidradenitis suppurativa (26%) was the most common condition associated with S. lugdunensis, followed by folliculitis, abscesses, ulcers, cellulitis, and acne. Co-infections with other bacteria were noted in 49.6% of cases, and 25.2% of infections were nosocomially acquired. The majority of patients (65%) received systemic antibiotics, predominantly amoxicillin/clavulanic acid, cefuroxime axetil, and doxycycline, with a cure rate of 100%. All isolates were susceptible to several antibiotics, though resistance to penicillin (28.5%) and clindamycin (36%) was observed. Conclusions:S. lugdunensis is a significant pathogen in skin infections, capable of causing severe disease. The high cure rate demonstrates the effectiveness of appropriate antibiotic therapy. Continued monitoring and antimicrobial stewardship are essential to manage resistance and ensure effective treatment.

11.
Molecules ; 29(15)2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39124894

RESUMEN

High-level erythromycin (ERY) fermentation wastewater will pose serious threats to lake environments. Anaerobic digestion (AD) has advantages in treating high-level antibiotic wastewater. However, the fate of antibiotic resistance genes (ARGs) and microbial communities in AD after stepwise exposure to high-level ERY remains unclear. In this study, an AD reactor was first exposed to 0, 5, 10, 50, 100 and 200 mg/L ERY and then re-exposed to 0, 50, 200 and 500 mg/L ERY to investigate the effect of ERY on AD. The results show that AD could adapt to the presence of high-level ERY (500 mg/L) and could maintain efficient CH4 production after domestication with low-level ERY (50 mg/L). The AD process could achieve higher removal of ERY (>94%), regardless of the initial ERY concentration. ErmB and mefA, conferring resistance through target alteration and efflux pumps, respectively, were dominant in the AD process. The first exposure to ERY stimulated an increase in the total ARG abundance, while the AD process seemed to discourage ARG maintenance following re-exposure to ERY. ERY inhibited the process of acetoclastic methanogenesis, but strengthened the process of hydrogenotrophic methanogenesis. This work provides useful information for treating high-level ERY fermentation wastewater by the AD process.


Asunto(s)
Reactores Biológicos , Eritromicina , Eritromicina/farmacología , Anaerobiosis/efectos de los fármacos , Aguas Residuales/microbiología , Fermentación , Antibacterianos/farmacología , Farmacorresistencia Microbiana/genética , Metano/metabolismo
12.
Int J Mol Sci ; 25(15)2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39125715

RESUMEN

The study investigates the antibiotic resistance (AR) profiles and genetic determinants in three strains of guaiacol-producing Alicyclobacillus spp. isolated from orchard soil and pears. Their phenotypic characteristics, such as spore formation; resistance to different factors, including drugs or disinfectants; or production of off-flavor compounds, can affect the taste and aroma of spoiled products. Food and beverages are potential vectors for the transfer of antibiotic resistance genes, which is a growing health concern; thus, microorganisms in food and beverages should not be a potential source of drug resistance to consumers. Whole-genome sequencing (WGS) was utilized to identify antibiotic resistance genes, metabolic pathways, and elements associated with guaiacol and halophenol production. Minimum inhibitory concentration (MIC) testing revealed that all strains were susceptible to eight out of nine tested antibiotics (ampicillin, gentamycin, kanamycin, streptomycin, clindamycin, tetracycline, chloramphenicol, and vancomycin) but exhibited high resistance to erythromycin. Analysis indicated that the erythromycin resistance gene, ribosomal RNA small subunit methyltransferase A (RsmA), was intrinsic and likely acquired through horizontal gene transfer (HGT). The comprehensive genomic analysis provides insights into the molecular mechanisms of antibiotic resistance in Alicyclobacillus spp., highlighting the potential risk of these bacteria as vectors for antibiotic resistance genes in the food chain. This study expands the understanding of the genetic makeup of these spoilage bacteria and their role in antimicrobial resistance dissemination.


Asunto(s)
Alicyclobacillus , Antibacterianos , Genoma Bacteriano , Pruebas de Sensibilidad Microbiana , Alicyclobacillus/genética , Alicyclobacillus/efectos de los fármacos , Antibacterianos/farmacología , Secuenciación Completa del Genoma , Farmacorresistencia Bacteriana/genética , Transferencia de Gen Horizontal , Guayacol/farmacología , Guayacol/análogos & derivados
13.
Water Environ Res ; 96(8): e11086, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39082880

RESUMEN

Conventional wastewater treatment plants (WWTPs) are not designed for the abatement of antibiotics, and their effluents are one of the main entry ways of these emerging contaminants to the aquatic environment, causing major concern due to their toxicity, persistence, and bioaccumulation. When wastewater containing antibiotics enters the bioreactor, they can impact microbial communities of the activated sludge, affecting biodegradation processes of organic matter and nutrients. There is scarce information about the effect of activated carbon on the activated sludge within the bioreactor in presence of antibiotics. In light of this, the effect of representative antibiotics, ciprofloxacin (CIP), nalidixic acid (NAL), and erythromycin (ERY), on the performance of a conventional activated sludge of a WWTP was analyzed by respirometry with and without activated carbon. NAL and ERY negatively affected the net heterotrophic biomass growth rate (r'x,H), with reduction percentages of 26%-90% and 31%-81%, respectively. The addition of activated carbon mitigated this effect, especially for ERY, with increments of even 8% in the r'x,H for the hybrid process when working with 5 ppm of ERY and 80 ppm of activated carbon compared with the value in the absence of antibiotic and activated carbon. This effect was attributed to the enhanced retention of ERY, in comparison to NAL, on the surface of the activated carbon, probably due to its higher molecular size and affinity towards the activated carbon (log Kow = 3.06). This effect was more marked at low sludge retention times (below 8 days). PRACTITIONER POINTS: Ciprofloxacin (CIP), nalidixic acid (NAL), and erythromycin (ERY) were studied. NAL and ERY exerted negative impact on heterotrophic growth rate. Effect of antibiotics on microorganisms in the presence of activated carbon was studied. Activated carbon was mainly relevant for ERY due to its adsorption retention. Enhancement by activated carbon was more significant at low sludge retention times.


Asunto(s)
Antibacterianos , Carbón Orgánico , Aguas del Alcantarillado , Antibacterianos/farmacología , Antibacterianos/química , Carbón Orgánico/química , Adsorción , Cinética , Contaminantes Químicos del Agua/química , Reactores Biológicos , Eliminación de Residuos Líquidos/métodos , Procesos Heterotróficos , Eritromicina/farmacología
14.
Structure ; 32(9): 1443-1453.e4, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39029461

RESUMEN

Mycobacterial HflX confers resistance against macrolide antibiotics. However, the exact molecular mechanism is poorly understood. To gain further insights, we determined the cryo-EM structures of M. smegmatis (Msm) HflX-50S subunit and 50S subunit-erythromycin (ERY) complexes at a global resolution of approximately 3 Å. A conserved nucleotide A2286 at the gate of nascent peptide exit tunnel (NPET) adopts a swayed conformation in HflX-50S complex and interacts with a loop within the linker helical (LH) domain of MsmHflX that contains an additional 9 residues insertion. Interestingly, the swaying of this nucleotide, which is usually found in the non-swayed conformation, is induced by erythromycin binding. Furthermore, we observed that erythromycin decreases HflX's ribosome-dependent GTP hydrolysis, resulting in its enhanced binding and anti-association activity on the 50S subunit. Our findings reveal how mycobacterial HflX senses the presence of macrolides at the peptide tunnel entrance and confers antibiotic resistance in mycobacteria.


Asunto(s)
Proteínas Bacterianas , Farmacorresistencia Bacteriana , Eritromicina , Modelos Moleculares , Mycobacterium smegmatis , Antibacterianos/farmacología , Antibacterianos/química , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Sitios de Unión , Microscopía por Crioelectrón , Eritromicina/farmacología , Eritromicina/química , Guanosina Trifosfato/metabolismo , Mycobacterium smegmatis/metabolismo , Mycobacterium smegmatis/efectos de los fármacos , Unión Proteica , Subunidades Ribosómicas Grandes Bacterianas/metabolismo , Subunidades Ribosómicas Grandes Bacterianas/química
15.
Methods Mol Biol ; 2844: 123-132, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39068336

RESUMEN

In situ promoter engineering is an effective way to alter target gene expression without introducing excess DNA sequences. Recently, the CRISPR/Cas9 technologies have been proved to be efficient tools for genome editing in actinomycetes, making it easier and more efficient to perform gene insertion and substitution in actinomycetes in a scarless manner. In this chapter, we describe a routine protocol for CRISPR/Cas9-mediated promoter engineering in Saccharopolyspora erythraea NRRL 23338, which is the wild-type producer of erythromycin. This protocol can be adapted to CRISPR/Cas9-mediated gene editing, not limited to promoter engineering, in other actinomycetes, with modifications.


Asunto(s)
Sistemas CRISPR-Cas , Edición Génica , Regiones Promotoras Genéticas , Saccharopolyspora , Saccharopolyspora/genética , Edición Génica/métodos , Ingeniería Genética/métodos , Eritromicina , ARN Guía de Sistemas CRISPR-Cas/genética
16.
Int J Mol Sci ; 25(14)2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39063169

RESUMEN

Implant surface nanofiber (NF) coatings represent an alternative way to prevent/treat periprosthetic joint infection (PJI) via local drug release. We developed and characterized a coaxial erythromycin (EM)-doped PLGA/PCL-PVA NF coating. The purpose of this study was to determine the efficacy of EM-NF coatings (EM0, no EM, EM100 (100 mg/mL), and EM1000 (1000 mg/mL) wt/wt) in a rat PJI model. A strong bond of the EM-NF coating to the surface of titanium (Ti) pins was confirmed by in vitro mechanical testing. Micro-computed tomography (mCT) analysis showed that both EM100 and EM1000 NF effectively reduced periprosthetic osteolysis compared to EM0 at 8 and 16 weeks after implantation. Histology showed that EM100 and EM1000 coatings effectively controlled infection and enhanced periprosthetic new bone formation. The bone implant contact (BIC) of EM100 (35.08%) was higher than negative controls and EM0 (3.43% and 0%, respectively). The bone area fraction occupancy (BAFO) of EM100 (0.63 mm2) was greater than controls and EM0 (0.390 mm2 and 0.0 mm2, respectively). The BAFO of EM100 was higher than that of EM1000 (0.3 mm2). These findings may provide a basis for a new implant surface fabrication strategy aimed at reducing the risks of defective osseointegration and PJI.


Asunto(s)
Materiales Biocompatibles Revestidos , Modelos Animales de Enfermedad , Eritromicina , Nanofibras , Infecciones Relacionadas con Prótesis , Infecciones Estafilocócicas , Staphylococcus aureus , Animales , Nanofibras/química , Ratas , Infecciones Relacionadas con Prótesis/tratamiento farmacológico , Infecciones Relacionadas con Prótesis/microbiología , Eritromicina/farmacología , Eritromicina/administración & dosificación , Materiales Biocompatibles Revestidos/farmacología , Materiales Biocompatibles Revestidos/química , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/administración & dosificación , Masculino , Titanio/química , Titanio/farmacología , Microtomografía por Rayos X , Ratas Sprague-Dawley
17.
Int J Biol Macromol ; 276(Pt 2): 133999, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39033898

RESUMEN

Erythromycin (ERY) molecules are robust to the environment and hard to remove due to their aromatic structure. Nowadays, numerous researches have reported that the ERY amount in water is above the standard level and its removal is necessary. Here, we prepared three solid adsorbents: graphitic carbon nitride (g-C3N4), potassium carrageenan beads (Cr), and graphitic carbon nitride/gum Arabic/potassium carrageenan composite (g-ACr). Several techniques such as XRD, SEM, TEM, TGA, ATR-FTIR, Zeta potential, and N2 adsorption were employed to characterize the fabricated adsorbents. Five essential factors of adsorbent dose, initial ERY concentration, contact time, temperature, and pH were optimized to investigate the batch adsorption of ERY. The maximum adsorption capacity of 356.12 mg/g was attained by g-ACr composite at an adsorbent dose of 1.25 g/L, contact time of 6 h, and pH 7 at 15 °C. The data showed that the experimental findings exhibited the best agreement with Langmuir, Temkin, and DR isotherm models, in addition to the kinetic models of pseudo-second-order, Elovich, and intra-particle diffusion. The evaluated thermodynamic factors designated that the ERY adsorption is endothermic, physisorption, favorable, and spontaneous process. The g-ACr reusability displayed a decline in the adsorption capacity after seven adsorption/desorption runs by 5.7 %. Finally, this work outcomes depict that g-ACr composite is an efficient reusable adsorbent for ERY elimination from wastewater.


Asunto(s)
Carragenina , Eritromicina , Grafito , Termodinámica , Contaminantes Químicos del Agua , Purificación del Agua , Adsorción , Grafito/química , Cinética , Carragenina/química , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/aislamiento & purificación , Eritromicina/química , Concentración de Iones de Hidrógeno , Purificación del Agua/métodos , Compuestos de Nitrógeno/química , Temperatura
18.
Eur J Med Chem ; 276: 116630, 2024 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-38972081

RESUMEN

We report here on the structure-activity relationships of hybrids combining 3-descladinosyl clarithromycin with quinolones linked by extended diamine connectors. Several hybrids, exemplified by 23Bc, 23Be, 23Bf, 26Be, and 30Bc, not only restored potency against inducibly resistant pathogens but also exhibited significantly enhanced activities against constitutively resistant strains of Staphylococcus pneumoniae and Staphylococcus pyogenes, which express high-level resistance independent of clarithromycin or erythromycin induction. Additionally, the novel hybrids showed susceptibility against Gram-negative Haemophilus influenzae. Notably, hybrid 23Be demonstrated dual modes of action by inhibiting both protein synthesis and DNA replication in vitro and in vivo. Given these promising characteristics, 23Be emerges as a potential candidate for the treatment of community-acquired bacterial pneumonia.


Asunto(s)
Antibacterianos , Claritromicina , Diseño de Fármacos , Pruebas de Sensibilidad Microbiana , Relación Estructura-Actividad , Claritromicina/farmacología , Claritromicina/química , Claritromicina/síntesis química , Antibacterianos/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Estructura Molecular , Diaminas/química , Diaminas/farmacología , Diaminas/síntesis química , Haemophilus influenzae/efectos de los fármacos , Oximas/química , Oximas/farmacología , Oximas/síntesis química , Relación Dosis-Respuesta a Droga , Humanos , Animales , Streptococcus pyogenes/efectos de los fármacos , Farmacorresistencia Bacteriana/efectos de los fármacos
19.
Artículo en Inglés | MEDLINE | ID: mdl-39021124

RESUMEN

Abstract: This retrospective study reviewed the macrolide resistance rates of Group A Streptococcus (GAS) isolates in the Northern Territory from 2012 to 2023. Clindamycin and erythromycin resistance rates peaked in 2021, at 6.0% and 12.2% respectively, and then returned to near baseline at 1-2% in 2023. Increased resistance rates were identified in the Top End of Australia from mid-2020, followed 15 months later by high rates in central Australia in 2022. Factors associated with resistant isolates were living in a rural region and of age 18 years and older. Possible explanations include a transient clonal introduction of a resistant GAS strain to the Northern Territory from 2020 to 2022. Ongoing surveillance is required to monitor regional trends and identify temporal variations in resistant isolates.


Asunto(s)
Antibacterianos , Clindamicina , Farmacorresistencia Bacteriana , Eritromicina , Infecciones Estreptocócicas , Streptococcus pyogenes , Clindamicina/farmacología , Humanos , Eritromicina/farmacología , Northern Territory/epidemiología , Streptococcus pyogenes/efectos de los fármacos , Antibacterianos/farmacología , Infecciones Estreptocócicas/epidemiología , Infecciones Estreptocócicas/microbiología , Infecciones Estreptocócicas/tratamiento farmacológico , Estudios Retrospectivos , Femenino , Adulto , Masculino , Adolescente , Persona de Mediana Edad , Niño , Adulto Joven , Preescolar , Anciano , Pruebas de Sensibilidad Microbiana , Lactante
20.
Environ Sci Pollut Res Int ; 31(35): 47801-47817, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39007974

RESUMEN

This study investigates the fate and transport dynamics of metformin (MTN) and erythromycin (ETM), both classified as pharmaceutical and personal care products (PPCPs), in a saturated sandy soil column using temporal moment analysis (TMA). The key flow and transport parameters, including Darcy velocity, longitudinal dispersivity, adsorption, and degradation coefficients, were analyzed. The results reveal that MTN, a highly mobile contaminant, is eliminated from the column in approximately 40 days, while ETM shows significant adsorption due to its hydrophobic and adsorptive nature. Darcy velocity significantly affects PPCP transport; a one-order magnitude change alters contaminant mass recovery at the column outlet by 88% for MTN and 39-fold for ETM. Longitudinal dispersivity has minimal impact on the transport of PPCPs. However adsorption primarily governs the fate of PPCPs with high adsorption coefficients (Kd), and degradation rates control the fate of low-sorbing PPCPs. A one-order magnitude change in Kd results in a 55% change in the zeroth temporal moment (ZTM) of MTN and a 30-fold change in the case of ETM. Additionally, a one-order magnitude change in the degradation coefficient leads to a 60% variation in MTN's ZTM and a 5% variation in ETM's ZTM. Thus, TMA is a valuable tool for understanding PPCP dynamics in subsurface environments, providing critical insights for managing their increasing concentrations.


Asunto(s)
Eritromicina , Metformina , Eritromicina/química , Adsorción , Porosidad , Suelo/química
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