Related Experiment Video
Updated: Mar 25, 2026
10:24
A Fluorescence-based Protocol for Preliminary Screening of Protein Synthesis Inhibitors from Natural Sources
Published on: January 27, 2026
415
Benzoxaborole-modified azithromycins inhibit translation without inducing ermC expression.
Inna A Volynkina1,2, Michael O Bortyazh1,3, Chih-Wei Chen4
1Department of Chemistry, Lomonosov Moscow State University, Moscow, Russia.
Antimicrobial Agents and Chemotherapy
|March 24, 2026
Summary
New antibacterial agents combat resistance by modifying azithromycin (AZI). These AZI-benzoxaborole conjugates inhibit bacterial translation and prevent resistance by altering ribosome interactions, unlike traditional macrolides.
Area of Science:
- Microbiology
- Medicinal Chemistry
- Molecular Biology
Background:
- Antimicrobial resistance necessitates novel antibacterial agents.
- Azithromycin (AZI) is a macrolide antibiotic scaffold for developing new drugs.
- Mechanisms of AZI derivatives are not fully understood.
Purpose of the Study:
- Characterize the activity and mechanism of novel AZI-benzoxaborole (AZI-BB) conjugates.
- Investigate their efficacy against macrolide-resistant bacteria.
- Elucidate how modifications affect ribosome interaction and resistance induction.
Main Methods:
- In vitro translation inhibition assays.
- Testing against an Escherichia coli strain with an inducible macrolide resistance operon.
- High-throughput toeprinting with deep sequencing (Toe-seq).
- Structural analysis of AZI-BB2-ribosome interactions.
Main Results:
- AZI-BB conjugates inhibit bacterial translation and retain activity against resistant E. coli.
- Compounds show minimal induction of the ErmC resistance protein.
- Structural analysis reveals unique interactions of AZI-BB2 with 23S rRNA, causing premature ribosome stalling.
- AZI-BB2 displays reduced sequence specificity for resistance-conferring motifs.
Conclusions:
- Targeted modification of AZI can alter its ribosome binding and attenuate resistance mechanisms.
- AZI-benzoxaborole conjugates represent a promising strategy for overcoming macrolide resistance.
- Understanding these mechanistic shifts is crucial for designing next-generation antibiotics.
Related Concept Videos
01:25Inhibitors of Bacterial Protein Synthesis
24
Aminoglycosides constitute a highly potent class of bactericidal antibiotics that exert their antimicrobial effects by targeting the bacterial ribosome, specifically disrupting protein synthesis. These polycationic molecules consist of amino-modified sugars linked via glycosidic bonds to an aminocyclitol core such as 2-deoxystreptamine or streptamine. Their strong positive charges facilitate tight binding to the negatively charged phosphate backbone of ribosomal RNA (rRNA), primarily at the 16S...
24
01:28Inhibitors of Bacterial DNA Synthesis
18
Bacterial pathogens depend on precise and efficient DNA replication to sustain infection. Two type II topoisomerases—DNA gyrase and topoisomerase IV—are critical to this process, as they resolve DNA supercoiling and unlink chromosomes during replication. Fluoroquinolones, synthetic derivatives of quinolones, exploit this mechanism by stabilizing the transient DNA–enzyme cleavage complex, preventing strand religation, and causing lethal double-strand breaks. These...
18
02:33Initiation of Translation
40.1K
Initiating translation is complex because it involves multiple molecules. Initiator tRNA, ribosomal subunits, and eukaryotic initiation factors (eIFs) are all required to assemble on the initiation codon of mRNA. This process consists of several steps that are mediated by different eIFs.
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...
40.1K
02:28Leaky Scanning
5.9K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.9K
01:52Eukaryotic Transcription Inhibitors
11.3K
Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
11.3K
01:23Inhibitors of Gram-positive Cell Wall Synthesis
22
Bacterial cell walls are typically rigid structures composed mainly of peptidoglycan, a mesh-like polymer that provides mechanical strength and maintains cell shape. The synthesis of peptidoglycan is a crucial process in bacterial growth and serves as a primary target for many antibiotics.Mechanism of Action of Beta-Lactam AntibioticsBeta-lactam antibiotics, such as penicillin, inhibit peptidoglycan synthesis in actively growing cells. These antibiotics share a characteristic four-membered...
22