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Biochemistry. Biokhimiia Dec 2010This review describes the results of recent studies of the ribosomal tunnel (RT), the major function of which is to allow the smooth passage of nascent polypeptides with... (Review)
Review
This review describes the results of recent studies of the ribosomal tunnel (RT), the major function of which is to allow the smooth passage of nascent polypeptides with different sequences from the peptidyl transferase center of the ribosome to the tunnel exit, where the folding of protein molecules begins. The features of structural organization of RT and their role in modulation and stabilization of the nascent chain conformation are discussed. Structural features of macrolide binding sites as well as application of macrolide antibiotics and their derivatives as tools to investigate ligand-tunnel wall interactions are also considered. Several examples of strong and specific interactions of regulatory polypeptides with nucleotide and amino acid residues of RT that lead to ribosome stalling and translational arrest are described in detail. The role of these events in regulation of expression of certain genes is discussed on the basis of recent high-resolution structural studies of nascent chains in the RT.
Topics: Animals; Anti-Bacterial Agents; Humans; Macrolides; Peptides; Peptidyl Transferases; Protein Biosynthesis; Protein Conformation; Ribosomes
PubMed: 21417991
DOI: 10.1134/s0006297910130018 -
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 -
Mediators of Inflammation 2012Long-term therapy with the macrolide antibiotic erythromycin was shown to alter the clinical course of diffuse panbronchiolitis in the late 1980s. Since that time,... (Review)
Review
Long-term therapy with the macrolide antibiotic erythromycin was shown to alter the clinical course of diffuse panbronchiolitis in the late 1980s. Since that time, macrolides have been found to have a large number of anti-inflammatory properties in addition to being antimicrobials. These observations provided the rationale for many studies performed to assess the usefulness of macrolides in other inflammatory diseases including skin and hair disorders, such as rosacea, psoriasis, pityriasis rosea, alopecia areata, bullous pemphigoid, and pityriasis lichenoides. This paper summarizes a collection of clinical studies and case reports dealing with the potential benefits of macrolides antibiotics in the treatment of selected dermatoses which have primarily been classified as noninfectious and demonstrating their potential for being disease-modifying agents.
Topics: Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Humans; Macrolides; Skin Diseases
PubMed: 22685371
DOI: 10.1155/2012/159354 -
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 -
Medicine Sep 2019The purpose of this study was to present the computed tomographic (CT) findings of lung abnormalities in macrolide-resistant Mycobacterium massiliense pulmonary disease... (Observational Study)
Observational Study
The purpose of this study was to present the computed tomographic (CT) findings of lung abnormalities in macrolide-resistant Mycobacterium massiliense pulmonary disease and its changes in follow-up CT after antibiotic treatment.Chest CT scans of patients with macrolide-resistant M massiliense pulmonary disease (n = 19) were retrospectively reviewed. Patients were treated with multidrug therapy, and sputum examinations were performed. Follow-up CT scans obtained during antibiotic treatment after detection of macrolide resistance were also reviewed, if available (n = 13). The CT scores at detection of macrolide resistance and at the last follow-up periods were also compared.Of all patients with macrolide-resistant M massiliense pulmonary disease, 2 (11%) patients achieved sputum culture conversion during the follow-up period. The most common CT findings of M massiliense pulmonary disease at detection of macrolide resistance were bronchiectasis and bronchiolitis (n = 19, 100%), followed by consolidation (n = 16, 84%), cavities (n = 11, 58%), and nodules (n = 6, 32%). On the last follow-up CT, overall CT scores were increased in 8 (62%) of 13 patients, and total mean CT score was significantly increased (P = .021). For each CT pattern, the cavity showed the greatest increase in CT score (P = .027), followed by bronchiectasis (P = .038).Common CT findings of macrolide-resistant M massiliense pulmonary disease were similar to those of pulmonary disease caused by other species of nontuberculous mycobacteria at presentation. However, in macrolide-resistant M massiliense pulmonary disease, serial CT scans showed deterioration with cavitary and bronchiectatic change in most patients despite multidrug antibiotic therapy.
Topics: Aged; Anti-Bacterial Agents; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Humans; Macrolides; Male; Middle Aged; Mycobacterium Infections, Nontuberculous; Mycobacterium abscessus; Respiratory Tract Diseases; Retrospective Studies; Sputum; Tomography, X-Ray Computed
PubMed: 31490369
DOI: 10.1097/MD.0000000000016826 -
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 -
Clinical Microbiology and Infection :... Apr 2009Antibiotic use in the treatment of respiratory tract infections is common in primary care. The European Surveillance of Antimicrobial Consumption (ESAC programme),... (Review)
Review
Antibiotic use in the treatment of respiratory tract infections is common in primary care. The European Surveillance of Antimicrobial Consumption (ESAC programme), collecting data from 35 countries, showed that antibiotic use was highest in southern European countries. Increased antibiotic consumption has been shown by numerous ecological studies to contribute to the emergence of antibiotic resistance in streptococci. A study comparing outpatient antibiotic consumption in the USA showed it to be similar to that in southern European countries, but macrolides, particularly azithromycin, are among the first-line agents prescribed in the USA for respiratory infections. In Europe, patients are more likely to receive a beta-lactam; and when a macrolide is indicated, clarithromycin is more likely to be prescribed than azithromycin. Streptococci resistance to macrolides can be acquired via two mechanisms: by the mef gene, which encodes for the efflux pump mechanism, producing low to moderate resistance, or the erm gene (post-transcriptional modification of the bacterial ribosomal unit), resulting in high resistance. Macrolide resistance is mediated by erm(B) and mef(A) alone or in combination. A surveillance study showed that mef was responsible for most of the macrolide resistance seen in the USA; a decrease in the number of isolates carrying mef(A) was associated with a doubling of the number of isolates carrying both mef(A) and erm(B). Higher consumption of clarithromycin in Europe correlated with a predominance of erm(B)-carrying Streptococcus pneumoniae. The erm(B) gene caused resistance in 84% of the isolates in Europe.
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Drug Therapy; Drug Utilization; Europe; Humans; Macrolides; Pneumococcal Infections; Selection, Genetic; Streptococcus pneumoniae; United States; beta-Lactams
PubMed: 19366364
DOI: 10.1111/j.1469-0691.2009.02725.x -
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... May 2014Randomized, controlled trials have demonstrated that chronic therapy with macrolide antibiotics reduces the morbidity of patients with cystic fibrosis, non-cystic... (Review)
Review
Randomized, controlled trials have demonstrated that chronic therapy with macrolide antibiotics reduces the morbidity of patients with cystic fibrosis, non-cystic fibrosis bronchiectasis, chronic obstructive pulmonary disease, and nontuberculous mycobacterial infections. Lower levels of evidence indicate that chronic macrolides are also effective in treating patients with panbronchiolitis, bronchiolitis obliterans, and rejection after lung transplant. Macrolides are known to cause torsade des pointes and other ventricular arrhythmias, and a recent observational study prompted the FDA to strengthen the Warnings and Precautions section of azithromycin drug labels. This summary describes the electrophysiological effects of macrolides, reviews literature indicating that the large majority of subjects experiencing cardiac arrhythmias from macrolides have coexisting risk factors and that the incidence of arrhythmias in absence of coexisting risk factors is very low, examines recently published studies describing the relative risk of arrhythmias from macrolides, and concludes that this risk has been overestimated and suggests an approach to patient evaluation that should reduce the relative risk and the incidence of arrhythmias to the point that chronic macrolides can be used safely in the majority of subjects for whom they are recommended.
Topics: Anti-Bacterial Agents; Arrhythmias, Cardiac; Azithromycin; Cystic Fibrosis; Heart Conduction System; Humans; Macrolides; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Risk Factors
PubMed: 24707986
DOI: 10.1164/rccm.201402-0385CI -
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