scholarly journals Extraction and Purification of Curcumin from Curcuma Longa and Its Effect on Multiple Drug Resistant Microbes

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zachary D. Aron ◽  
Atousa Mehrani ◽  
Eric D. Hoffer ◽  
Kristie L. Connolly ◽  
Pooja Srinivas ◽  
...  

AbstractBacterial ribosome rescue pathways that remove ribosomes stalled on mRNAs during translation have been proposed as novel antibiotic targets because they are essential in bacteria and are not conserved in humans. We previously reported the discovery of a family of acylaminooxadiazoles that selectively inhibit trans-translation, the main ribosome rescue pathway in bacteria. Here, we report optimization of the pharmacokinetic and antibiotic properties of the acylaminooxadiazoles, producing MBX-4132, which clears multiple-drug resistant Neisseria gonorrhoeae infection in mice after a single oral dose. Single particle cryogenic-EM studies of non-stop ribosomes show that acylaminooxadiazoles bind to a unique site near the peptidyl-transfer center and significantly alter the conformation of ribosomal protein bL27, suggesting a novel mechanism for specific inhibition of trans-translation by these molecules. These results show that trans-translation is a viable therapeutic target and reveal a new conformation within the bacterial ribosome that may be critical for ribosome rescue pathways.


2005 ◽  
Vol 26 (5) ◽  
pp. 968-975 ◽  
Author(s):  
Cho-Hwa Liao ◽  
Shiow-Lin Pan ◽  
Jih-Hwa Guh ◽  
Ya-Ling Chang ◽  
Hui-Chen Pai ◽  
...  

2011 ◽  
Vol 77 (19) ◽  
pp. 6755-6762 ◽  
Author(s):  
Chia-Ni Lee ◽  
Tsai-Tien Tseng ◽  
Juey-Wen Lin ◽  
Yung-Chieh Fu ◽  
Shu-Fen Weng ◽  
...  

ABSTRACTAcinetobacter baumanniiis an important Gram-negative opportunistic pathogen causing nosocomial infections. The emergence of multiple-drug-resistantA. baumanniiisolates has increased in recent years. Directed toward phage therapy, a lytic phage ofA. baumannii, designated Abp53, was isolated from a sputum sample in this study. Abp53 has an isometric head and a contractile tail with tail fibers (belonging toMyoviridae), a latent period of about 10 min, and a burst size of approximately 150 PFU per infected cell. Abp53 could completely lyse 27% of theA. baumanniiisolates tested, which were all multiple drug resistant, but not other bacteria. Mg2+enhanced the adsorption and productivity of, and host lysis by, Abp53. Twenty Abp53 virion proteins were visualized in SDS-polyacrylamide gel electrophoresis, with a 47-kDa protein being the predicted major capsid protein. Abp53 has a double-stranded DNA genome of 95 kb. Sequence analyses of a 10-kb region revealed 8 open reading frames. Five of the encoded proteins, including 3 tail components and 2 hypothetical proteins, were similar to proteins encoded byA. baumanniistrain ACICU. ORF1176 (one of the tail components, 1,176 amino acids [aa]), which is also similar to tail protein gp21 ofKlebsiellaphage phiKO2, contained repeated domains similar to those within the ACICU_02717 protein ofA. baumanniiACICU and gp21. These findings suggest a common ancestry and horizontal gene transfer during evolution. As phages can expand the host range by domain duplication in tail fiber proteins, repeated domains in ORF1176 might have a similar significance in Abp53.


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