The macrolide antibiotic renaissance
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TLDR
A recent published breakthrough introduced a new chemical platform for synthesis and discovery of a wide range of diverse macrolides, leading to a macrolide renaissance, increasing the hope for novel and safe therapeutic agents to combat serious human infectious diseases.Abstract:
Macrolides represent a large family of protein synthesis inhibitors of great clinical interest due to their applicability to human medicine. Macrolides are composed of a macrocyclic lactone of different ring sizes, to which one or more deoxy-sugar or amino sugar residues are attached. Macrolides act as antibiotics by binding to bacterial 50S ribosomal subunit and interfering with protein synthesis. The high affinity of macrolides for bacterial ribosomes, together with the highly conserved structure of ribosomes across virtually all of the bacterial species, is consistent with their broad-spectrum activity. Since the discovery of the progenitor macrolide, erythromycin, in 1950, many derivatives have been synthesised, leading to compounds with better bioavailability and acid stability and improved pharmacokinetics. These efforts led to the second generation of macrolides, including well-known members such as azithromycin and clarithromycin. Subsequently, in order to address increasing antibiotic resistance, a third generation of macrolides displaying improved activity against many macrolide resistant strains was developed. However, these improvements were accompanied with serious side effects, leading to disappointment and causing many researchers to stop working on macrolide derivatives, assuming that this procedure had reached the end. In contrast, a recent published breakthrough introduced a new chemical platform for synthesis and discovery of a wide range of diverse macrolide antibiotics. This chemical synthesis revolution, in combination with reduction in the side effects, namely, 'Ketek effects', has led to a macrolide renaissance, increasing the hope for novel and safe therapeutic agents to combat serious human infectious diseases.read more
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Journal ArticleDOI
Microbial Resistance Movements: An Overview of Global Public Health Threats Posed by Antimicrobial Resistance, and How Best to Counter.
Sameer Dhingra,Nor Azlina A Rahman,Ed Peile,Motiur Rahman,Massimo Sartelli,Mohamed Azmi Hassali,Tariqul Islam,Salequl Islam,Mainul Haque +8 more
TL;DR: Suggestions on how to address this public health threat are suggested, including recommendations on training medical students about antibiotics, and strategies to overcome the problems of irrational antibiotic prescribing and AMR are concluded.
Journal ArticleDOI
Adverse events in people taking macrolide antibiotics versus placebo for any indication.
Malene Plejdrup Hansen,Anna Mae Scott,Amanda McCullough,Sarah Thorning,Jeffrey K Aronson,Elaine Beller,Paul Glasziou,Tammy Hoffmann,Justin Clark,Chris Del Mar +9 more
TL;DR: The incidences of reported adverse events in people taking macrolide antibiotics compared to placebo for any indication were quantified to quantify the risk of bias and the quality of evidence for each outcome of interest.
Journal ArticleDOI
Ribosome protection by antibiotic resistance ATP-binding cassette protein.
Weixin Su,Veerendra Kumar,Yichen Ding,Rya Ero,Aida Serra,Benjamin Sian Teck Lee,Andrew S.W. Wong,Jian Shi,Siu Kwan Sze,Liang Yang,Yong-Gui Gao,Yong-Gui Gao +11 more
TL;DR: Characterization of MsrE protein bound to the bacterial ribosome is first of its kind for ARE ABC-F members, and sheds light on the ribosomal protection mechanism by domain linker-mediated conformational change and displacement leading to drug release, suggesting a mechanism shared by other AREABC-F proteins.
Journal ArticleDOI
Structure of Erm-modified 70S ribosome reveals the mechanism of macrolide resistance
Maxim S. Svetlov,Egor A Syroegin,Elena V. Aleksandrova,Gemma C. Atkinson,Steven T. Gregory,Alexander S. Mankin,Yury S. Polikanov +6 more
TL;DR: In this paper, the crystal structure of the Erm-dimethylated 70S ribosome at 2.4-4-A resolution was presented, together with the structures of unmethylated and 23S rRNA nucleotide A2058-based 70S-ribosome functional complexes alone or in combination with macrolides.
Journal ArticleDOI
Application of Antibiotics/Antimicrobial Agents on Dental Caries.
Wei Qiu,Wei Qiu,Yujie Zhou,Zixin Li,Tu Huang,Yuhan Xiao,Lei Cheng,Xian Peng,Lixin Zhang,Lixin Zhang,Biao Ren +10 more
TL;DR: This review focuses on the application of systemic antibiotics and other antimicrobial agents with respect to their clinical use to date, including the history of their development, and their side effects, uses, structure types, and molecular mechanisms to promote a better understanding of the importance of microbial interactions in dental plaque and combinational treatments.
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