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Medicina (Kaunas, Lithuania) Oct 2023is a bacterial species often associated with the occurrence of community-acquired pneumonia (CAP). CAP refers to a specific kind of pneumonia that occurs in individuals... (Review)
Review
is a bacterial species often associated with the occurrence of community-acquired pneumonia (CAP). CAP refers to a specific kind of pneumonia that occurs in individuals who acquire the infection outside of a healthcare setting. It represents the leading cause of both death and morbidity on a global scale. Moreover, the declaration of as one of the 12 leading pathogens was made by the World Health Organization (WHO) in 2017. Antibiotics like -lactams, macrolides, and fluoroquinolones are the primary classes of antimicrobial medicines used for the treatment of infections. Nevertheless, the efficacy of these antibiotics is diminishing as a result of the establishment of resistance in against these antimicrobial agents. In 2019, the WHO declared that antibiotic resistance was among the top 10 hazards to worldwide health. It is believed that penicillin-binding protein genetic alteration causes -lactam antibiotic resistance. Ribosomal target site alterations and active efflux pumps cause macrolide resistance. Numerous factors, including the accumulation of mutations, enhanced efflux mechanisms, and plasmid gene acquisition, cause fluoroquinolone resistance. Furthermore, despite the advancements in pneumococcal vaccinations and artificial intelligence (AI), it is not feasible for individuals to rely on them indefinitely. The ongoing development of AI for combating antimicrobial resistance necessitates more research and development efforts. A few strategies can be performed to curb this resistance issue, including providing educational initiatives and guidelines, conducting surveillance, and establishing new antibiotics targeting another part of the bacteria. Hence, understanding the resistance mechanism of may aid researchers in developing a more efficacious antibiotic in future endeavors.
Topics: Humans; Anti-Bacterial Agents; Streptococcus pneumoniae; Fluoroquinolones; beta-Lactams; Macrolides; Artificial Intelligence; Drug Resistance, Bacterial; Pneumonia; Anti-Infective Agents; Community-Acquired Infections
PubMed: 38003976
DOI: 10.3390/medicina59111927 -
Journal of the American Chemical Society Sep 2020Lankacidins are a class of polyketide natural products isolated from that show promising antimicrobial activity. Owing to their complex molecular architectures and...
Lankacidins are a class of polyketide natural products isolated from that show promising antimicrobial activity. Owing to their complex molecular architectures and chemical instability, structural assignment and derivatization of lankacidins are challenging tasks. Herein we describe three fully synthetic approaches to lankacidins that enable access to new structural variability within the class. We use these routes to systematically generate stereochemical derivatives of both cyclic and acyclic lankacidins. Additionally, we access a new series of lankacidins bearing a methyl group at the C4 position, a modification intended to increase chemical stability. In the course of this work, we discovered that the reported structures for two natural products of the lankacidin class were incorrect, and we determine the correct structures of 2,18--lankacidinol B and -lankacidinol. We also evaluate the ability of several - and -lankacidins to inhibit the growth of bacteria and to inhibit translation in vitro. This work grants insight into the rich chemical complexity of this class of antibiotics and provides an avenue for further structural derivatization.
Topics: Anti-Bacterial Agents; Bacillus subtilis; Crystallography, X-Ray; Macrolides; Microbial Sensitivity Tests; Micrococcus; Models, Molecular; Molecular Structure; Staphylococcus aureus; Stereoisomerism; Streptomyces
PubMed: 32786797
DOI: 10.1021/jacs.0c06648 -
Emerging Infectious Diseases Oct 2020Macrolide-resistant Bordetella pertussis emerged in Vietnam during 2016-2017. Direct analyses of swab samples from 10 patients with pertussis revealed a...
Macrolide-resistant Bordetella pertussis emerged in Vietnam during 2016-2017. Direct analyses of swab samples from 10 patients with pertussis revealed a macrolide-resistant mutation, A2047G, in the 23S rRNA. We identified the MT104 genotype of macrolide-resistant B. pertussis (which is prevalent in mainland China) and its variants in these patients.
Topics: Anti-Bacterial Agents; Bordetella pertussis; China; Drug Resistance, Bacterial; Erythromycin; Humans; Macrolides; RNA, Ribosomal, 23S; Vietnam
PubMed: 32946738
DOI: 10.3201/eid2610.201035 -
Proceedings of the National Academy of... Dec 2022Although lacking an adaptive immune system and often living in habitats with dense and diverse bacterial populations, marine invertebrates thrive in the presence of...
Although lacking an adaptive immune system and often living in habitats with dense and diverse bacterial populations, marine invertebrates thrive in the presence of potentially challenging microbial pathogens. However, the mechanisms underlying this resistance remain largely unexplored and promise to reveal novel strategies of microbial resistance. Here, we provide evidence that a mud-dwelling clam, s, synthesizes, stores, and secretes the antibiotic erythromycin. Liquid chromatography coupled with mass spectrometry, immunocytochemistry, fluorescence in situ hybridization, RNA interference, and enzyme-linked immunosorbent assay revealed that this potent macrolide antimicrobial, thought to be synthesized only by microorganisms, is produced by specific mucus-rich cells beneath the clam's mantle epithelium, which interfaces directly with the bacteria-rich environment. The antibacterial activity was confirmed by bacteriostatic assay. Genetic, ontogenetic, phylogenetic and genomic evidence, including genotypic segregation ratios in a family of full siblings, gene expression in clam larvae, phylogenetic tree, and synteny conservation in the related genome region further revealed that the genes responsible for erythromycin production are of animal origin. The detection of this antibiotic in another clam species showed that the production of this macrolide is not exclusive to and may be a common strategy among marine invertebrates. The finding of erythromycin production by a marine invertebrate offers a striking example of convergent evolution in secondary metabolite synthesis between the animal and bacterial domains. These findings open the possibility of engineering-animal tissues for the localized production of an antibacterial secondary metabolite.
Topics: Animals; Erythromycin; Phylogeny; In Situ Hybridization, Fluorescence; Bivalvia; Anti-Bacterial Agents; Macrolides
PubMed: 36442100
DOI: 10.1073/pnas.2214150119 -
The European Respiratory Journal Jul 2013Long-term macrolide treatment was first shown to alter the natural history of diffuse panbronchiolitis (DPB) in the late 1980s. Since then, macrolides have been... (Review)
Review
Long-term macrolide treatment was first shown to alter the natural history of diffuse panbronchiolitis (DPB) in the late 1980s. Since then, macrolides have been demonstrated to exert anti-inflammatory and immunomodulatory activity in addition to being antimicrobial. Indeed, their spectrum of action extends to the regulation of leukocyte function and production of inflammatory mediators, control of mucus hypersecretion, resolution of inflammation and modulation of host defence mechanisms. As such, the potential benefit of macrolide antibiotics has been evaluated in a variety of chronic respiratory diseases. The best studied condition is cystic fibrosis, of which there have been six randomised controlled trials showing evidence of benefit. However, most of the studies were limited by small numbers of patients and short follow-up. More recently, landmark studies have demonstrated the efficacy of azithromycin in reducing the risk of acute exacerbations in patients with chronic obstructive pulmonary disease, but the optimal duration and dosing of macrolide treatment remain uncertain. With the exception of patients with DPB and cystic fibrosis, until clear evidence of efficacy is available, the long-term use of macrolides should be limited to highly selected patients after careful evaluation of benefit and harm, or in the context of randomised controlled clinical trials.
Topics: Anti-Bacterial Agents; Asthma; Bronchiectasis; Bronchiolitis; Bronchiolitis Obliterans; Chronic Disease; Clinical Trials as Topic; Cystic Fibrosis; Haemophilus Infections; Humans; Macrolides; Pneumonia; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Infections; Sinusitis
PubMed: 23180583
DOI: 10.1183/09031936.00136712 -
Journal of the Pediatric Infectious... Feb 2018Pneumonia, most often caused by a respiratory virus, is common in childhood. Mycoplasma pneumoniae also is detected frequently, particularly in older children in the era... (Review)
Review
Pneumonia, most often caused by a respiratory virus, is common in childhood. Mycoplasma pneumoniae also is detected frequently, particularly in older children in the era of pneumococcal conjugate vaccination. Despite recommendations for β-lactam antibiotics, macrolide antibiotics, including erythromycin, clarithromycin, and azithromycin, are prescribed frequently to children with acute lower respiratory infection. However, the significance of detecting "atypical" pathogens, including M pneumoniae, in children remains contentious. Considering the potential for antibacterial and anti-inflammatory activities of macrolides, our understanding of the role of these drugs in acute and chronic infections and in inflammatory conditions is changing. Some observational data have revealed improved outcomes in adults and children with pneumonia who are prescribed macrolides, although its widespread use has led to increases in macrolide resistance in Streptococcus pneumoniae and M pneumoniae. Clinical trials to define the role of macrolides in pediatric acute respiratory infection must be prioritized.
Topics: Anti-Bacterial Agents; Child; Community-Acquired Infections; Humans; Macrolides; Pneumonia, Bacterial; Treatment Outcome
PubMed: 29096010
DOI: 10.1093/jpids/pix083 -
Advanced Drug Delivery Reviews May 2022Drug carriers to deliver macrolide antibiotics, such as azithromycin, show promise as antibacterial agents. Macrolide drug carriers have largely focused on improving the... (Review)
Review
Drug carriers to deliver macrolide antibiotics, such as azithromycin, show promise as antibacterial agents. Macrolide drug carriers have largely focused on improving the drug stability and pharmacokinetics, while reducing adverse reactions and improving antibacterial activity. Recently, macrolides have shown promise in treating inflammatory conditions by promoting a reparative effect and limiting detrimental pro-inflammatory responses, which shifts the immunologic setpoint from suppression to balance. While macrolide drug carriers have only recently been investigated for their ability to modulate immune responses, the previous strategies that deliver macrolides for antibacterial therapy provide a roadmap for repurposing the macrolide drug carriers for therapeutic interventions targeting inflammatory conditions. This review describes the antibacterial and immunomodulatory activity of macrolides, while assessing the past in vivo evaluation of drug carriers used to deliver macrolides with the intention of presenting a case for increased effort to translate macrolide drug carriers into the clinic.
Topics: Anti-Bacterial Agents; Azithromycin; Drug Carriers; Humans; Macrolides
PubMed: 35367307
DOI: 10.1016/j.addr.2022.114252 -
Sheng Wu Gong Cheng Xue Bao = Chinese... Sep 2021Macrolide antibiotics are a class of broad-spectrum antibiotics with the macrolide as core nucleus. Recently, antibiotic pollution has become an important environmental... (Review)
Review
Macrolide antibiotics are a class of broad-spectrum antibiotics with the macrolide as core nucleus. Recently, antibiotic pollution has become an important environmental problem due to the irregular production and abuse of macrolide antibiotics. Microbial degradation is one of the most effective methods to deal with antibiotic pollution. This review summarizes the current status of environmental pollution caused by macrolide antibiotics, the degradation strains, the degradation enzymes, the degradation pathways and the microbial processes for degrading macrolide antibiotics. Moreover, the critical challenges on the biodegradation of macrolide antibiotics were also discussed.
Topics: Anti-Bacterial Agents; Biodegradation, Environmental; Macrolides
PubMed: 34622622
DOI: 10.13345/j.cjb.200714 -
Nature Communications Jul 2021Macrolides and ketolides comprise a family of clinically important antibiotics that inhibit protein synthesis by binding within the exit tunnel of the bacterial...
Macrolides and ketolides comprise a family of clinically important antibiotics that inhibit protein synthesis by binding within the exit tunnel of the bacterial ribosome. While these antibiotics are known to interrupt translation at specific sequence motifs, with ketolides predominantly stalling at Arg/Lys-X-Arg/Lys motifs and macrolides displaying a broader specificity, a structural basis for their context-specific action has been lacking. Here, we present structures of ribosomes arrested during the synthesis of an Arg-Leu-Arg sequence by the macrolide erythromycin (ERY) and the ketolide telithromycin (TEL). Together with deep mutagenesis and molecular dynamics simulations, the structures reveal how ERY and TEL interplay with the Arg-Leu-Arg motif to induce translational arrest and illuminate the basis for the less stringent sequence-specific action of ERY over TEL. Because programmed stalling at the Arg/Lys-X-Arg/Lys motifs is used to activate expression of antibiotic resistance genes, our study also provides important insights for future development of improved macrolide antibiotics.
Topics: Amino Acid Motifs; Amino Acid Sequence; Anti-Bacterial Agents; Bacillus subtilis; Binding Sites; Cryoelectron Microscopy; Drug Resistance, Microbial; Erythromycin; Genes, Bacterial; Ketolides; Macrolides; Methyltransferases; Molecular Dynamics Simulation; Mutagenesis, Insertional; Protein Biosynthesis; Protein Synthesis Inhibitors; Ribosomes
PubMed: 34294725
DOI: 10.1038/s41467-021-24674-9 -
Respirology (Carlton, Vic.) May 2018
Topics: Anti-Bacterial Agents; Community-Acquired Infections; Drug Therapy, Combination; Humans; Macrolides; Pneumonia; Pneumonia, Bacterial; beta-Lactams
PubMed: 29278281
DOI: 10.1111/resp.13248