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Sheng Wu Gong Cheng Xue Bao = Chinese... Aug 2023Tacrolimus (FK506) is a 23-membered macrolide with immunosuppressant activity that is widely used clinically for treating the rejection after organ transplantation. The... (Review)
Review
Tacrolimus (FK506) is a 23-membered macrolide with immunosuppressant activity that is widely used clinically for treating the rejection after organ transplantation. The research on tacrolimus production was mainly focused on biosynthesis methods, within which there are still some bottlenecks. This review summarizes the progress made in tacrolimus biosynthesis modification of metabolic pathways and control of fermentation process, with the hope to address the technical bottlenecks for tacrolimus biosynthesis and improve tacrolimus production by fermentation engineering and metabolic engineering.
Topics: Tacrolimus; Immunosuppressive Agents; Fermentation; Macrolides; Anti-Bacterial Agents
PubMed: 37622350
DOI: 10.13345/j.cjb.220994 -
Frontiers in Cellular and Infection... 2023With the widespread use of macrolide antibiotics in China, common pathogens causing children's infections, such as , (including , ), , , and , have shown varying... (Review)
Review
With the widespread use of macrolide antibiotics in China, common pathogens causing children's infections, such as , (including , ), , , and , have shown varying degrees of drug resistance. In order to provide such problem and related evidence for rational use of antibiotics in clinic, we reviewed the drug resistance of common bacteria to macrolides in children recent 20 years.
Topics: Drug Resistance, Bacterial; Macrolides; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Humans; Child; China
PubMed: 37637457
DOI: 10.3389/fcimb.2023.1181633 -
Marine Drugs Apr 2019Currently, the increasing resistance of microorganisms to antibiotics is a serious problem. Marine organisms are the source of thousands of substances, which also have... (Review)
Review
Currently, the increasing resistance of microorganisms to antibiotics is a serious problem. Marine organisms are the source of thousands of substances, which also have antibacterial and antifungal effects. Among them, marine macrolides are significant. In this review, the antibacterial and/or antifungal activities of 34 groups of marine macrolides are presented. Exemplary groups are chalcomycins, curvulides, halichondramides, lobophorins, macrolactins, modiolides, scytophycins, spongistatins, or zearalanones. In the paper, 74 antibiotics or their analog sets, among which 29 with antifungal activity, 25 that are antibacterial, and 20 that are both antifungal and antibacterial are summarized. Also, 36 macrolides or their sets are produced by bacteria, 18 by fungi, ten by sponges, seven by algae, two by porifera, and one by nudibranch. Moreover, the chemical structures of representatives from each of the 34 groups of these antibiotics are presented. To summarize, marine organisms are rich in natural macrolides. Some of these may be used in the future in the treatment of bacterial and fungal infections. Marine macrolides can also be potential drugs applicable against pathogens resistant to currently known antibiotics.
Topics: Animals; Anti-Bacterial Agents; Antifungal Agents; Aquatic Organisms; Bacteria; Fungi; Humans; Macrolides
PubMed: 31018512
DOI: 10.3390/md17040241 -
International Journal of Molecular... Oct 2020Macrolide antibiotics are macrocyclic compounds that are clinically used and prescribed for the treatment of upper and lower respiratory tract infections. They inhibit... (Review)
Review
Macrolide antibiotics are macrocyclic compounds that are clinically used and prescribed for the treatment of upper and lower respiratory tract infections. They inhibit the synthesis of bacterial proteins by reversible binding to the 23S rRNA at or near the peptidyl transferase center. However, their excellent antibacterial profile was largely compromised by the emergence of bacterial resistance. Today, fighting resistance to antibiotics is one of the greatest challenges in medicinal chemistry. Considering various physicochemical properties of macrolides, understanding their structure and interactions with macromolecular targets is crucial for the design of new antibiotics efficient against resistant pathogens. The solid-state structures of some macrolide-ribosome complexes have recently been solved, throwing new light on the macrolide binding mechanisms. On the other hand, a combination of NMR spectroscopy and molecular modeling calculations can be applied to study free and bound conformations in solution. In this article, a description of advanced physicochemical methods for elucidating the structure and interactions of macrolide antibiotics in solid state and solution will be provided, and their principal advantages and drawbacks will be discussed.
Topics: Anti-Bacterial Agents; Computer Simulation; Cryoelectron Microscopy; Crystallography, X-Ray; Macrolides; Magnetic Resonance Spectroscopy; Molecular Dynamics Simulation; Ribosomes
PubMed: 33096889
DOI: 10.3390/ijms21207799 -
Environmental Science and Pollution... Apr 2022Macrolide antibiotics (MAs), as a typical emerging pollutant, are widely detected in environmental media. When entering the environment, MAs can interfere with the... (Review)
Review
Macrolide antibiotics (MAs), as a typical emerging pollutant, are widely detected in environmental media. When entering the environment, MAs can interfere with the growth, development and reproduction of organisms, which has attracted extensive attention. However, there are few reviews on the occurrence characteristics, migration and transformation law, ecotoxicity and related removal technologies of MAs in the environment. In this work, combined with the existing relevant research, the migration and transformation law and ecotoxicity characteristics of MAs in the environment are summarized, and the removal mechanism of MAs is clarified. Currently, most studies on MAs are based on laboratory simulation experiments, and there are few studies on the migration and transformation mechanism between multiphase states. In addition, the cost of MAs removal technology is not satisfactory. Therefore, the following suggestions are put forward for the future research direction. The migration and transformation process of MAs between multiphase states (such as soil-water-sediment) should be focused on. Apart from exploring the new treatment technology of MAs, the upgrading and coupling of existing MAs removal technologies to meet emission standards and reduce costs should also be concerned. This review provides some theoretical basis and data support for understanding the occurrence characteristics, ecotoxicity and removal mechanism of MAs.
Topics: Anti-Bacterial Agents; Environmental Pollutants; Macrolides; Soil; Water Pollutants, Chemical
PubMed: 35067882
DOI: 10.1007/s11356-021-18251-2 -
Journal of Natural Products Dec 2022A series of novel macrolides were discovered from the culture supernatant of the rare soil actinobacteria and named dactylosporolides A-C. The structure and absolute...
A series of novel macrolides were discovered from the culture supernatant of the rare soil actinobacteria and named dactylosporolides A-C. The structure and absolute configuration of these dactylosporolides were defined using a combination of NMR structural elucidation and analysis of the dactylosporolide biosynthetic gene cluster. Together these data revealed dactylosporolides to be composed of a central 22-membered macrolactone with an internal hemiketal ring and a protruding ketide tail that were (poly)glycosylated at two distal parts. While bearing no antibiotic activity, these dactylosporolides displayed activity against 3D7.
Topics: Macrolides; Micromonosporaceae; Actinobacteria; Glycosylation; Anti-Bacterial Agents
PubMed: 36512509
DOI: 10.1021/acs.jnatprod.2c00484 -
Revista Espanola de Quimioterapia :... Jun 2023Mycoplasma pneumoniae is a bacterium that lacks a cell wall. It produces infections all It produces infections world-wide, in epidemic outbreaks every 4-7 years, or... (Review)
Review
Mycoplasma pneumoniae is a bacterium that lacks a cell wall. It produces infections all It produces infections world-wide, in epidemic outbreaks every 4-7 years, or endemically. Its clinical manifestations occur mostly in the respiratory tract and it is a common cause of atypical pneumonia. The treatment is with macrolides, tetracyclines or fluoroquinolones. Since 2000, an increase in resistance to macrolides has been detected worldwide, being more frequent in Asia. In Europe the frequency of resistance ranges between 1% and 25%, depending on the country. Molecular techniques and serology techniques provides very high sensitivity in diagnostic confirmation, being very useful for detecting and controlling M. pneumoniae outbreaks. The detection of resistance to macrolides requires a sequencing technique.
Topics: Humans; Mycoplasma pneumoniae; Macrolides; Drug Resistance, Bacterial; Pneumonia, Mycoplasma; Anti-Bacterial Agents; Europe
PubMed: 36966384
DOI: 10.37201/req/118.2022 -
Microbiology Spectrum Feb 2023Bacillus halodurans C-125 is an alkaliphilic microorganism that grows best at pH 10 to 10.5. . C-125 harbors the (erythromycin resistance methylase) gene as well as...
Bacillus halodurans C-125 is an alkaliphilic microorganism that grows best at pH 10 to 10.5. . C-125 harbors the (erythromycin resistance methylase) gene as well as the (macrolide phosphotransferase) and putative (macrolide efflux) genes, which confer resistance to macrolide, lincosamide, and streptogramin B (MLS) antibiotics. The Erm protein expressed in . C-125 could be classified as ErmK because it shares 66.2% and 61.2% amino acid sequence identity with the closest ErmD and Erm(34), respectively. ErmK can be regarded as a dimethylase, as evidenced by reverse transcriptase analysis and the antibiotic resistance profile exhibited by E. coli expressing . Although ErmK showed one-third or less methylating activity compared to ErmC', E. coli cells expressing ErmK exhibited comparable resistance to erythromycin and tylosin, and a similar dimethylation proportion of 23S rRNA due to the higher expression rate in a T7 promoter-mediated expression system. The less efficient methylation activity of ErmK might reflect an adaption to mitigate the fitness cost caused by dimethylation through the Erm protein presumably because . C-125 has less probability to encounter the antibiotics in its favorable growth conditions and grows retardedly in neutral environments. Erm proteins confer MLS antibiotic resistance (minimal inhibitory concentration [MIC] value up to 4,096 μg/mL) on microorganisms ranging from antibiotic producers to pathogens, imposing one of the most pressing threats to clinics. Therefore, Erm proteins have long been speculated to be plausible targets for developing inhibitor(s). In our laboratory, it has been noticed that there are variations in enzymatic activity among the Erm proteins, Erm in antibiotic producers being better than that in pathogens. In this study, it has been observed that Erm protein in . C-125 extremophile is a novel member of Erm protein and acts more laggardly, compared to that in pathogen. While this sluggishness of Erm protein in extremophile might be evolved to reduce the fitness cost incurred by Erm activity adapting to its environments, this feature could be exploited to develop the more potent and/or efficacious drug to combat formidably problematic antibiotic-resistant pathogens.
Topics: Escherichia coli; Anti-Bacterial Agents; Erythromycin; Macrolides; Microbial Sensitivity Tests
PubMed: 36511701
DOI: 10.1128/spectrum.02598-22 -
American Journal of Respiratory and... Oct 2019
Topics: Anti-Bacterial Agents; Azithromycin; Double-Blind Method; Hospitalization; Humans; Macrolides; Patient Readmission; Pulmonary Disease, Chronic Obstructive
PubMed: 31188635
DOI: 10.1164/rccm.201905-0957ED -
International Journal of Molecular... May 2023Various chronic inflammatory airway diseases can be treated with low-dose, long-term (LDLT) macrolide therapy. LDLT macrolides can be one of the therapeutic options for... (Review)
Review
Various chronic inflammatory airway diseases can be treated with low-dose, long-term (LDLT) macrolide therapy. LDLT macrolides can be one of the therapeutic options for chronic rhinosinusitis (CRS) due to their immunomodulatory and anti-inflammatory actions. Currently, various immunomodulatory mechanisms of the LDLT macrolide treatment have been reported, as well as their antimicrobial properties. Several mechanisms have already been identified in CRS, including reduced cytokines such as interleukin (IL)-8, IL-6, IL-1β, tumor necrosis factor-α, transforming growth factor-β, inhibition of neutrophil recruitment, decreased mucus secretion, and increased mucociliary transport. Although some evidence of effectiveness for CRS has been published, the efficacy of this therapy has been inconsistent across clinical studies. LDLT macrolides are generally believed to act on the non-type 2 inflammatory endotype of CRS. However, the effectiveness of LDLT macrolide treatment in CRS is still controversial. Here, we reviewed the immunological mechanisms related to CRS in LDLT macrolide therapy and the treatment effects according to the clinical situation of CRS.
Topics: Humans; Macrolides; Anti-Bacterial Agents; Sinusitis; Treatment Outcome; Cytokines; Chronic Disease; Rhinitis
PubMed: 37298439
DOI: 10.3390/ijms24119489