scholarly journals The evolution of substrate discrimination in macrolide antibiotic resistance enzymes

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Andrew C. Pawlowski ◽  
Peter J. Stogios ◽  
Kalinka Koteva ◽  
Tatiana Skarina ◽  
Elena Evdokimova ◽  
...  
2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Derek K-H. Ho ◽  
Christian Sawicki ◽  
Nicholas Grassly

Trachoma is caused byChlamydia trachomatisand is a leading cause of blindness worldwide. Mass distribution of azithromycin (AZM) is part of the strategy for the global elimination of blinding trachoma by 2020. Although resistance to AZM inC. trachomatishas not been reported, there have been concerns about resistance in other organisms when AZM is administered in community settings. We identified studies that measured pneumococcal prevalence and resistance to AZM following mass AZM provision reported up to 2013 in Medline and Web of Science databases. Potential sources of bias were assessed using the Cochrane Risk of Bias Tool. A total of 45 records were screened, of which 8 met the inclusion criteria. We identified two distinct trends of resistance prevalence, which are dependent on frequency of AZM provision and baseline prevalence of resistance. We also demonstrated strong correlation between the prevalence of resistance at baseline and at 2-3 months (r=0.759). Although resistance to AZM inC. trachomatishas not been reported, resistance to this commonly used macrolide antibiotic in other diseases could compromise treatment. This should be considered when planning long-term trachoma control strategies.


2016 ◽  
Vol 54 (9) ◽  
pp. 2278-2283 ◽  
Author(s):  
Damon Getman ◽  
Alice Jiang ◽  
Meghan O'Donnell ◽  
Seth Cohen

The prevalence rates ofMycoplasma genitaliuminfections and coinfections with other sexually transmitted organisms and the frequency of a macrolide antibiotic resistance phenotype were determined in urogenital specimens collected from female and male subjects enrolled in a multicenter clinical study in the United States. Specimens from 946 subjects seeking care from seven geographically diverse clinical sites were tested forM. genitaliumand forChlamydia trachomatis,Neisseria gonorrhoeae, andTrichomonas vaginalis. Sequencing was used to assess macrolide antibiotic resistance amongM. genitalium-positive subjects.M. genitaliumprevalence rates were 16.1% for females and 17.2% for males. Significant risk factors forM. genitaliuminfections were black race, younger age, non-Hispanic ethnicity, and female symptomatic status. FemaleM. genitaliuminfections were significantly more prevalent thanC. trachomatisandN. gonorrhoeaeinfections, while theM. genitaliuminfection rate in males was significantly higher than theN. gonorrhoeaeandT. vaginalisinfection rates. The macrolide-resistant phenotype was found in 50.8% of females and 42% of males. These results show a high prevalence ofM. genitaliumsingle infections, a lower prevalence of coinfections with other sexually transmitted organisms, and high rates of macrolide antibiotic resistance in a diverse sample of subjects seeking care across a wide geographic area of the United States.


2017 ◽  
Vol 31 (2) ◽  
pp. 195-201 ◽  
Author(s):  
Alexandra M. Mancuso ◽  
Mona A. Gandhi ◽  
Judianne Slish

Solithromycin is a macrolide antibiotic that has undergone review for the treatment of community-acquired bacterial pneumonia. Solithromycin is also being investigated and has shown promise for the treatment of gonorrhea. With increasing antibiotic resistance, the development of novel antibiotics to combat infections is essential. The unique ribosome-binding stability of solithromycin and mild side effect profile make this a promising new antibiotic. This article will provide an overview on the mechanism of action, clinical efficacy, and safety of this drug for the treatment of gonorrhea. Relevant data were identified through a comprehensive literature search using multiple databases using the keywords solithromycin, CEM-101, and gonorrhea.


Author(s):  
Dagmar Graber ◽  
Krista Trappl ◽  
Jessica Steger ◽  
Anna-Skrollan Geiermann ◽  
Lukas Rigger ◽  
...  

Structure ◽  
2017 ◽  
Vol 25 (5) ◽  
pp. 750-761.e5 ◽  
Author(s):  
Desiree H. Fong ◽  
David L. Burk ◽  
Jonathan Blanchet ◽  
Amy Y. Yan ◽  
Albert M. Berghuis

2018 ◽  
Vol 9 (11) ◽  
pp. 971-975 ◽  
Author(s):  
Qingqing Zhang ◽  
Huijuan Liu ◽  
Xiang Liu ◽  
Dunquan Jiang ◽  
Bingjie Zhang ◽  
...  

Author(s):  
S.L. White ◽  
C.B. Jensen ◽  
D.D. Giera ◽  
D.A. Laska ◽  
M.N. Novilla ◽  
...  

In vitro exposure to LY237216 (9-Deoxo-11-deoxy-9,11-{imino[2-(2-methoxyethoxy)ethylidene]-oxy}-(9S)-erythromycin), a macrolide antibiotic, was found to induce cytoplasmic vacuolation in L6 skeletal muscle myoblast cultures (White, S.L., unpubl). The present study was done to determine, by autoradiographic quantitative analysis, the subcellular distribution of 3H-LY237216 in L6 cells.L6 cells (ATCC, CRL 1458) were cultured to confluency on polycarbonate membrane filters (Millipore Corp., Bedford, MA) in M-199 medium (GIBCO® Labs) with 10% fetal bovine serum. The cells were exposed from the apical surface for 1-hour to unlabelled-compound (0 μCi/ml) or 50 (μCi/ml of 3H-LY237216 at a compound concentration of 0.25 mg/ml. Following a rapid rinse in compound-free growth medium, the cells were slam-frozen against a liquid nitrogen cooled, polished copper block in a CF-100 cryofixation unit (LifeCell Corp., The Woodlands, TX). Specimens were dried in the MDD-C Molecular Distillation Drier (LifeCell Corp.), vapor osmicated and embedded in Spurrs low viscosity resin. Ultrathin sections collected on formvar coated stainless steel grids were counter-stained, then individually mounted on corks. A monolayer of Ilford L4 nuclear emulsion (Polysciences, Inc., Warrington, PA) was placed on the sections, utilizing a modified “loop method”. The emulsions were exposed for 7-weeks in a light-tight box at 4°C. Autoradiographs were developed in Microdol-X developer and examined on a Philips EM410LS transmission electron microscope. Quantitative analysis of compound localization employed the point and circle approach of Williams; incorporating the probability circle method of Salpeter and McHenry.


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