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The Journal of Veterinary Medical... Nov 2022American foulbrood (AFB) is a honeybee disease caused by Paenibacillus larvae, and tylosin is used as the prophylactic in Japan. Honey contains macrolide-resistant...
American foulbrood (AFB) is a honeybee disease caused by Paenibacillus larvae, and tylosin is used as the prophylactic in Japan. Honey contains macrolide-resistant bacteria that are a potential source of genes that may confer tylosin resistance to P. larvae. To investigate the potential risk of such genes in Japanese honey, we developed real-time PCR assays for the detection of important macrolide resistance genes, ermC and ermB, and analyzed 116 Japanese honey samples with known contamination status of P. larvae. Consequently, 91.38% of samples contained ermC and/or ermB, and 71.55% of samples contained both ermC and P. larvae, suggesting the possible emergence of tylosin-resistant P. larvae in Japan. Therefore, judicious use of the prophylactic is essential in maintaining its effectiveness.
Topics: Bees; United States; Animals; Macrolides; Anti-Bacterial Agents; Tylosin; Honey; Japan; Real-Time Polymerase Chain Reaction; Drug Resistance, Bacterial; Larva
PubMed: 36123020
DOI: 10.1292/jvms.22-0307 -
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 -
Scientific Reports Apr 2020Macrolactones, macrocyclic lactones with at least twelve atoms within the core ring, include diverse natural products such as macrolides with potent bioactivities (e.g....
Macrolactones, macrocyclic lactones with at least twelve atoms within the core ring, include diverse natural products such as macrolides with potent bioactivities (e.g. antibiotics) and useful drug-like characteristics. We have developed MacrolactoneDB, which integrates nearly 14,000 existing macrolactones and their bioactivity information from different public databases, and new molecular descriptors to better characterize macrolide structures. The chemical distribution of MacrolactoneDB was analyzed in terms of important molecular properties and we have utilized three targets of interest (Plasmodium falciparum, Hepatitis C virus and T-cells) to demonstrate the value of compiling this data. Regression machine learning models were generated to predict biological endpoints using seven molecular descriptor sets and eight machine learning algorithms. Our results show that merging descriptors yields the best predictive power with Random Forest models, often boosted by consensus or hybrid modeling approaches. Our study provides cheminformatics insights into this privileged, underexplored structural class of compounds with high therapeutic potential.
Topics: Biological Products; Cheminformatics; Databases, Chemical; Machine Learning; Macrolides; Models, Chemical; Quantitative Structure-Activity Relationship; Software
PubMed: 32286395
DOI: 10.1038/s41598-020-63192-4 -
PloS One 2023Macrolide usage in Japan exceeds that in Europe and the United States. Investigating the actual conditions in which macrolides are used is important for identifying... (Review)
Review
Macrolide usage in Japan exceeds that in Europe and the United States. Investigating the actual conditions in which macrolides are used is important for identifying further interventions for appropriate antimicrobial use; however, this situation has not been evaluated in Japan. Therefore, we aimed to clarify the number of macrolide prescriptions and their changes before and after implementation of the Antimicrobial Resistance (AMR) Action Plan. In addition, we also investigated the names of diseases for which macrolides have been prescribed and the number of days of prescription. A retrospective observational study was conducted using JMDC claims data from January 2013 to December 2018. The proportion of all oral antimicrobials and macrolides used during this period and the diseases for which macrolides were used in the 3 years before and after the AMR Action Plan were determined separately for acute (< 14 prescription days) and chronic (> 14 prescription days) diseases. The number of prescriptions for macrolides constituted approximately 30% of those for all oral antimicrobials; of these, clarithromycin accounted for approximately 60%. Most prescriptions for acute diseases were for common cold, whereas allergic and dermatological diseases were included among chronic diseases. The names of these illnesses did not change before and after the AMR Action Plan. Overall, these results indicate that appropriate macrolide use involves a review of their use for common cold along with appropriate evaluation of their long-term use for skin and allergic diseases. They also indicate the need for further fact-finding studies and ongoing AMR measures.
Topics: Humans; Macrolides; Common Cold; Retrospective Studies; Japan; Anti-Bacterial Agents; Anti-Infective Agents; Prescriptions; Hypersensitivity; Observational Studies as Topic
PubMed: 37347735
DOI: 10.1371/journal.pone.0287297 -
BMC Microbiology Aug 2023The microbiome of the human gut serves a role in a number of physiological processes, but can be altered through effects of age, diet, and disturbances such as...
BACKGROUND
The microbiome of the human gut serves a role in a number of physiological processes, but can be altered through effects of age, diet, and disturbances such as antibiotics. Several studies have demonstrated that commonly used antibiotics can have sustained impacts on the diversity and the composition of the gut microbiome. The impact of the two most overused antibiotics, azithromycin, and amoxicillin, in the human microbiome has not been thoroughly described. In this study, we recruited a group of individuals and unrelated controls to decipher the effects of the commonly used antibiotics amoxicillin and azithromycin on their gut microbiomes.
RESULTS
We characterized the gut microbiomes by metagenomic sequencing followed by characterization of the resulting microbial communities. We found that there were clear and sustained effects of the antibiotics on the gut microbial community with significant alterations in the representations of Bifidobacterium species in response to azithromycin (macrolide antibiotic). These results were supported by significant increases identified in putative antibiotic resistance genes associated with macrolide resistance. Importantly, we did not identify these trends in the unrelated control individuals. There were no significant changes observed in other members of the microbial community.
CONCLUSIONS
As we continue to focus on the role that the gut microbiome plays and how disturbances induced by antibiotics might affect our overall health, elucidating members of the community most affected by their use is of critical importance to understanding the impacts of common antibiotics on those who take them. Clinical Trial Registration Number NCT05169255. This trial was retrospectively registered on 23-12-2021.
Topics: Humans; Anti-Bacterial Agents; Amoxicillin; Azithromycin; Metagenomics; Macrolides; Drug Resistance, Bacterial
PubMed: 37528343
DOI: 10.1186/s12866-023-02949-z -
Chemico-biological Interactions Sep 2022The sea is a vast ecosystem that has remained primarily unexploited and untapped, resulting in numerous organisms. Consequently, marine organisms have piqued the... (Review)
Review
The sea is a vast ecosystem that has remained primarily unexploited and untapped, resulting in numerous organisms. Consequently, marine organisms have piqued the interest of scientists as an abundant source of natural resources with unique structural features and fascinating biological activities. Marine macrolide is a top-class natural product with a heavily oxygenated polyene backbone containing macrocyclic lactone. In the last few decades, significant efforts have been made to isolate and characterize macrolides' chemical and biological properties. Numerous macrolides are extracted from different marine organisms such as marine microorganisms, sponges, zooplankton, molluscs, cnidarians, red algae, tunicates, and bryozoans. Notably, the prominent macrolide sources are fungi, dinoflagellates, and sponges. Marine macrolides have several bioactive characteristics such as antimicrobial (antibacterial, antifungal, antimalarial, antiviral), anti-inflammatory, antidiabetic, cytotoxic, and neuroprotective activities. In brief, marine organisms are plentiful in naturally occurring macrolides, which can become the source of efficient and effective therapeutics for many diseases. This current review summarizes these exciting and promising novel marine macrolides in biological activities and possible therapeutic applications.
Topics: Animals; Anti-Bacterial Agents; Aquatic Organisms; Biological Products; Cnidaria; Ecosystem; Macrolides; Porifera
PubMed: 35952775
DOI: 10.1016/j.cbi.2022.110072 -
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 -
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 -
Microbial Cell Factories Aug 2019Actinobacteria are characterized as the most prominent producer of natural products (NPs) with pharmaceutical importance. The production of NPs from these actinobacteria... (Review)
Review
Actinobacteria are characterized as the most prominent producer of natural products (NPs) with pharmaceutical importance. The production of NPs from these actinobacteria is associated with particular biosynthetic gene clusters (BGCs) in these microorganisms. The majority of these BGCs include polyketide synthase (PKS) or non-ribosomal peptide synthase (NRPS) or a combination of both PKS and NRPS. Macrolides compounds contain a core macro-lactone ring (aglycone) decorated with diverse functional groups in their chemical structures. The aglycon is generated by megaenzyme polyketide synthases (PKSs) from diverse acyl-CoA as precursor substrates. Further, post-PKS enzymes are responsible for allocating the structural diversity and functional characteristics for their biological activities. Macrolides are biologically important for their uses in therapeutics as antibiotics, anti-tumor agents, immunosuppressants, anti-parasites and many more. Thus, precise genetic/metabolic engineering of actinobacteria along with the application of various chemical/biological approaches have made it plausible for production of macrolides in industrial scale or generation of their novel derivatives with more effective biological properties. In this review, we have discussed versatile approaches for generating a wide range of macrolide structures by engineering the PKS and post-PKS cascades at either enzyme or cellular level in actinobacteria species, either the native or heterologous producer strains.
Topics: Actinobacteria; Biological Products; Genetic Engineering; Macrolides; Multigene Family; Polyketide Synthases; Polyketides
PubMed: 31409353
DOI: 10.1186/s12934-019-1184-z -
Journal of Global Antimicrobial... Dec 2023Group B Streptococcus (GBS) has emerged as an important cause of severe infections in adults. However, limited data are available regarding the epidemiology of GBS in...
OBJECTIVES
Group B Streptococcus (GBS) has emerged as an important cause of severe infections in adults. However, limited data are available regarding the epidemiology of GBS in Saudi Arabia.
METHODS
Isolates were collected over a period of eight months from colonized (n = 104) and infected adults (n = 95). Serotypes and virulence determinants were detected by polymerase chain reactions (PCRs). Genetic relatedness was assessed using Multiple Locus Variable Number Tandem Repeat Analysis (MLVA). Antimicrobial susceptibilities were determined by disk diffusion.
RESULTS
Serotypes III and V (25% each) were the most prevalent, followed by serotypes II (16.18%), Ia (13.24%), VI (9.31%), and Ib (8.82%), while five isolates remained non-typeable (2.45%). Hypervirulent serotype III/CC17 clone (n = 21) accounted for 41.18% of the serotype III isolates. Most isolates (53.92%) harboured pilus island (PI) 1 and 2a types, while PI-2b was predominantly detected in the hypervirulent clone. Isolates were variably resistant to tetracycline (76.47%), erythromycin (36.76%), clindamycin (25.49%), and levofloxacin (6.37%), but remained susceptible to penicillin. Macrolide resistant isolates exhibited constitutive (55.42%) and inducible macrolide-lincosamide-streptogramin B resistance phenotypes (33.74%), while a few had L (9.64%) or M (1.2%) phenotypes. MLVA patterns of dominant serotypes III and V revealed 40 different types divided into 12 clusters and 28 singletons. Interestingly, macrolide resistance was significantly associated with two major MLVA types.
CONCLUSIONS
GBS isolates belonged predominantly to serotypes III and V, but there were no clear associations between serotypes and patient groups. The studied isolates exhibited high levels of resistance to erythromycin and clindamycin that need further surveillance.
Topics: Adult; Humans; Anti-Bacterial Agents; Clindamycin; Streptococcal Infections; Saudi Arabia; Serotyping; Drug Resistance, Bacterial; Macrolides; Erythromycin; Molecular Typing; Streptococcus agalactiae
PubMed: 37844802
DOI: 10.1016/j.jgar.2023.10.007