Clindamycin and Lincomycin
M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson in Kucers’ The Use of Antibiotics, 2017
Clindamycin-resistant bacteria usually have the MLS resistance phenotype. This type of resistance is associated with genes encoding for the ribosomal methyltransferases leading to modification of the common target site for macrolides and lincosamides. The common target site is the 23S ribosomal RNA. This makes the ribosome insensitive to the actions of clindamycin. The rRNA methylases are encoded by erm (erythromycin ribosome methylase) genes, known as erm(A) or erm(C) genes (Spizek and Rezanka, 2004). These genes can be acquired through mobile elements and can be found on the bacterial chromosome or on plasmids. These erm genes can be transferred among species and confer a much more pronounced MLS-type resistance than those of spontaneous mutations (Clabots et al., 1988; Hachler et al., 1987; Halula and Macrina, 1990; Privitera et al., 1981, 1979; Tally and Malamy, 1986). Over 30 classes of erm genes have been identified (Roberts, 2004). The incidence of each class of erm genes differs among bacterial species and geographic location. For example, in staphylococci the erm(A) and erm(C) genes predominate, but in streptococci the erm(B) gene is most common.
Oxazolidinones and Streptogramins
Thomas T. Yoshikawa, Shobita Rajagopalan in Antibiotic Therapy for Geriatric Patients, 2005
Thus far, resistance to linezolid and quinupristin/dalfopristin has been rare among gram-positive organisms. No cross-resistance between other protein synthesis inhibitors and linezolid has been described, as had been predicted by virtue of linezolid's unique mechanism of action. Gram-positive bacteria with de novo resistance to both linezolid and quinupristin/dalfopristin have been described. This has more frequently been the case with quinupristin/dalfopristin, probably because of streptogramin use in livestock in certain parts of the world. More important, it is possible to generate resistance to both linezolid and quinupristin/dalfopristin in the laboratory, and the emergence of resistance to both agents has also occurred in vivo during therapy. The emergence of resistant isolates during therapy can be associated with treatment failure. For linezolid, the emergence of resistance has been more common in enterococci than in staphylococci (11). The mechanism of resistance against linezolid appears to involve mutations in the 23S portion of the ribosomal RNA, which lies within the 50S subunit. The change in the 23S ribosomal RNA presumably alters the oxazolidinone binding site. Clinical conditions that increase the risk of the development of resistant strains include prolonged therapy, sequestered sites of infection, and device-related infections.
Neonatal ocular prophylaxis in the United States: is it still necessary?
Published in Expert Review of Anti-infective Therapy, 2023
Susannah Franco, Margaret R. Hammerschlag
Erythromycin, the oldest antibiotic of the broad-spectrum macrolide class, exhibits its bacteriostatic action by binding to the 50S bacterial ribosomal subunit. This prevents the formation of peptide bonds and consequently the translocation of the peptidyl-tRNA. Binding to the 50S ribosomal subunit also blocks the peptide exit channel by interacting with 23S ribosomal RNA (rRNA) located within the 50S ribosomal subunit. Protein synthesis is ultimately inhibited due to the incomplete release of polypeptides from the bacterial ribosomes [20–22]. Bacterial resistance mechanisms against macrolides are thought to be genetic, either via specific nucleotide alterations in 23S rRNA or through modifications of the 23S rRNA subunit by rRNA methylases that prevent macrolide binding. Another theorized resistance mechanism is an overexpression of efflux pumps, particularly the MtrCDE efflux pump [20].
An overview of nanotechnology-based treatment approaches against Helicobacter Pylori
Published in Expert Review of Anti-infective Therapy, 2019
Tural Safarov, Bukre Kiran, Melahat Bagirova, Adil M Allahverdiyev, Emrah Sefik Abamor
Amoxicillin, a member of the penicillin family, is an antibiotic containing a beta-lactam ring used to treat H.Pylori [33]. The main mechanisms leading to resistance to amoxicillin antibiotic are thought to be alterations in binding proteins, reduced cell membrane permeability of the antibiotic, or a combined effect of these factors [34]. Clarithromycin is one of the basic drugs used in the treatment of H.Pylori [35]. One of the most important factors of failure in H.Pylori eradication is the resistance to clarithromycin. Resistance to clarithromycin acting by binding to the peptidyl transferase cycle of the V region of the 23S ribosomal RNA molecule developed by point mutations in the 23S rRNA [36]. Metronidazole, a bactericidal antibiotic, is a synthetic nitroimidazole [27]. The synthetic nitroimidazole antibiotic, metronidazole, is activated by nitroreductases in the cytosol of the microorganism [37]. Mutations cause inactivation of these nitroreductases. This leads to the development of resistance [37].
Binding site comparisons for target-centered drug discovery
Published in Expert Opinion on Drug Discovery, 2019
Janez Konc
Like proteins, non-coding RNAs achieve their specific biological functions by folding into three-dimensional structures. RNA structural motifs have many important functions, for example, the kink-turn motifs on bacterial 23S ribosomal RNA (rRNA) are binding sites for nine proteins [80] and the universally conserved sarcin-ricin loop on 23S rRNA contains sites that are recognized and cleaved by ribotoxins [81]. Many methods for comparing RNA motifs exist [82–85] but a comparison of RNA motifs is not as widely used in drug design as protein binding site comparison. Its use, however, may increase as more new disease roles of RNAs are discovered. In addition, there are currently more than 7,000 protein-nucleic acid structures in the PDB, and this number is growing rapidly [33].
Related Knowledge Centers
- Antimicrobial Resistance
- Chloramphenicol
- Escherichia Coli
- Nucleotide
- Peptidyl Transferase
- Ribosomal Rna
- Prokaryotic Large Ribosomal Subunit
- Lsu Rrna
- 28S Ribosomal Rna
- 5.8S Ribosomal Rna