• Title/Summary/Keyword: Ribosomal Antibiotics

Search Result 29, Processing Time 0.019 seconds

Ribosomal Crystallography: Peptide Bond Formation, Chaperone Assistance and Antibiotics Activity

  • Yonath, Ada
    • Molecules and Cells
    • /
    • v.20 no.1
    • /
    • pp.1-16
    • /
    • 2005
  • The peptidyl transferase center (PTC) is located in a protein free environment, thus confirming that the ribosome is a ribozyme. This arched void has dimensions suitable for accommodating the 3'ends of the A-and the P-site tRNAs, and is situated within a universal sizable symmetry-related region that connects all ribosomal functional centers involved in amino-acid polymerization. The linkage between the elaborate PTC architecture and the A-site tRNA position revealed that the A-to P-site passage of the tRNA 3'end is performed by a rotatory motion, which leads to stereochemistry suitable for peptide bond formation and for substrate mediated catalysis, thus suggesting that the PTC evolved by genefusion. Adjacent to the PTC is the entrance of the protein exit tunnel, shown to play active roles in sequence-specific gating of nascent chains and in responding to cellular signals. This tunnel also provides a site that may be exploited for local co-translational folding and seems to assist in nascent chain trafficking into the hydrophobic space formed by the first bacterial chaperone, the trigger factor. Many antibiotics target ribosomes. Although the ribosome is highly conserved, subtle sequence and/or conformational variations enable drug selectivity, thus facilitating clinical usage. Comparisons of high-resolution structures of complexes of antibiotics bound to ribosomes from eubacteria resembling pathogens, to an archaeon that shares properties with eukaryotes and to its mutant that allows antibiotics binding, demonstrated the unambiguous difference between mere binding and therapeutical effectiveness. The observed variability in antibiotics inhibitory modes, accompanied by the elucidation of the structural basis to antibiotics mechanism justifies expectations for structural based improved properties of existing compounds as well as for the development of novel drugs.

Resistance of Kanamycin- and Neomycin-Producing Streptomycetes to Aminoglycoside Antibiotics

  • Goo, Yang-Mo;Choi, Seok-Rye;Kim, Kyung-Ja
    • Bulletin of the Korean Chemical Society
    • /
    • v.15 no.7
    • /
    • pp.568-571
    • /
    • 1994
  • Streptmyces fradiae NRRL B1195 and Streptomyces kanamyceticus IFO 13414 are highly resistant to the antibiotics they produce. The ribosomes of these organisms are found to be susceptible to the antibiotics, but the cell free extract of S fradiae is found to contain a phosphotransferase and an acetyltransferase which inactivate kanamycin and neomycin, and that of S. kanamyceticus an acetyltransferse which inactivates kanamycin and neomycin. The resistance of these organisms against streptomycin is found to be due to the resistant ribosomes; actually streptomycin activates their ribosomal systems for the synthesis of polyphenylalanine.

Gut-residing Microbes Alter the Host Susceptibility to Autoantibody-mediated Arthritis

  • Lee, Hyerim;Jin, Bo-Eun;Jang, Eunkyeong;Lee, A Reum;Han, Dong Soo;Kim, Ho-Youn;Youn, Jeehee
    • IMMUNE NETWORK
    • /
    • v.14 no.1
    • /
    • pp.38-44
    • /
    • 2014
  • K/BxN serum can transfer arthritis to normal mice owing to the abundant autoantibodies it contains, which trigger innate inflammatory cascades in joints. Little is known about whether gut-residing microbes affect host susceptibility to autoantibody-mediated arthritis. To address this, we fed C57BL/6 mice with water containing a mixture of antibiotics (ampicillin, vancomycin, neomycin, and metronidazol) for 2 weeks and then injected them with K/BxN serum. Antibiotic treatment significantly reduced the amount of bacterial genomic DNA isolated from fecal samples, in particular a gene encoding 16S ribosomal RNA derived from segmented filamentous bacteria. Arthritic signs, as indicated by the arthritic index and ankle thickness, were significantly attenuated in antibiotic-treated mice compared with untreated controls. Peyer's patches and mesenteric lymph nodes from antibiotic-treated mice contained fewer IL-17-expressing cells than those from untreated mice. Antibiotic treatment reduced serum C3 deposition in vitro via the alternative complement pathway. IL-$17^{-/-}$ congenic C57BL/6 mice were less susceptible to K/BxN serum-transferred arthritis than their wild-type littermates, but were still responsive to treatment with antibiotics. These results suggest that gut-residing microbes, including segmented filamentous bacteria, induce IL-17 production in GALT and complement activation via the alternative complement pathway, which cause the host to be more susceptible to autoantibody-mediated arthritis.

Management of Infections with Rapidly Growing Mycobacteria after Unexpected Complications of Skin and Subcutaneous Surgical Procedures

  • Lim, Jong-Min;Kim, Jong-Hwan;Yang, Ho-Jik
    • Archives of Plastic Surgery
    • /
    • v.39 no.1
    • /
    • pp.18-24
    • /
    • 2012
  • Background : Infection caused by rapidly growing mycobacteria (RGM) is not uncommon, and the prevalence of RGM infection has been increasing. Clinical diagnosis is difficult because there are no characteristic clinical features. There is also no standard antibiotic regimen for treating RGM infection. A small series of patients with RGM infections was studied to examine their treatments and outcomes. Methods : A total of 5 patients who had developed postoperative infections from January 2009 to December 2010 were retrospectively reviewed. Patients were initially screened using a mycobacteria rapid screening test (polymerase chain reaction [PCR]-reverse blot hybridization assay). To confirm mycobacterial infection, specimens were cultured for nontuberculous mycobacteria and analyzed by 16 S ribosomal RNA and rpoB gene PCR. Results : The patients were treated with intravenous antibiotics during hospitalization, and oral antibiotics were administered after discharge. The mean duration of follow-up was 9 months, and all patients were completely cured of infection with a regimen of a combination of antibiotics plus surgical treatment. Although none of the patients developed recurrence, there were complications at the site of infection, including hypertrophic scarring, pigmentation, and disfigurement. Conclusions : Combination antibiotic therapy plus drainage of surgical abscesses appeared to be effective for the RGM infections seen in our patients. Although neither the exact dosage nor a standardized regimen has been firmly established, we propose that our treatment can provide an option for the management of rapidly growing mycobacterial infection.

Effect of Antibiotics upon the Antibacterial Activity of Platelet Microbicidal Protein against Streptococcus rattus BHT

  • Kim, Jae-Wook;Choe, Son-Jin;Lee, Si-Young
    • International Journal of Oral Biology
    • /
    • v.34 no.1
    • /
    • pp.43-48
    • /
    • 2009
  • Thrombin-induced platelet microbicidal protein (tPMP) is a small cationic peptide that exerts potent in vitro microbicidal activity against a broad spectrum of human pathogens, including Staphylococcus aureus and Streptococcus rattus BHT. Earlier evidence has suggested that tPMP targets and disrupts the bacterial membrane. However, it is not yet clear whether membrane disruption itself is sufficient to kill the bacteria or whether subsequent, presumably intracellular, events are also involved in this process. In this study, we investigated the microbicidal activity of rabbit tPMP toward S. rattus BHT cells in the presence or absence of a pretreatment with antibiotics that differ in their mechanisms of action. The streptocidal effects of tPMP on control cells (no antibiotic pretreatment) were rapid and concentration-dependent. Pretreatment of S. rattus BHT cells with either penicillin or amoxicillin (inhibitors of bacterial cell wall synthesis) significantly enhanced the anti-S. rattus BHT effects of tPMP compared with the effects against the respective control cells over most tPMP concentration ranges tested. On the other hand, pretreatment of S. rattus BHT cells with tetracycline or doxycycline (30S ribosomal subunit inhibitors) significantly decreased the streptocidal effects of tPMP over a wide peptide concentration range. Furthermore, pretreatment with rifampin (an inhibitor of DNA-dependent RNA polymerase) essentially blocked the killing of S. rattus BHT by tPMP at most concentrations compared with the respective control cells. These results suggest that tPMP exerts anti-S. rattus BHT activity through mechanisms involving both the cell membrane and intracellular targets.

Comparison of Expression Profiles between Trophozoite and Cyst of Acanthamoeba castellanii

  • Moon, Eun-Kyung;Kong, Hyun-Hee
    • Biomedical Science Letters
    • /
    • v.18 no.3
    • /
    • pp.313-318
    • /
    • 2012
  • Acanthamoeba is an opportunistic pathogen known to cause granulomatous amoebic encephalitis and amebic keratitis. Acanthamoeba exhibits life cycle consisting of trophozoite and cyst, and the cyst is highly resistant to variable antibiotics and therapeutic agents. To understand the encystation mechanism of Acanthamoeba, the expression profiles of trophozoite and cyst were compared by gene ontology (GO) analysis. Ribosomal proteins and cytoskeletal proteins were highly expressed in trophozoite. In cyst, various protease, and signal transduction - and protein turnover - related proteins were highly expressed. These results correlated with eukaryotic orthologous groups (KOG) assignment and microarray analysis of Acanthamoeba trophozoite and cyst ESTs. The information of differential expression profiles of trophozoite and cyst would provide important clues for research on encystation mechanism of cyst forming protozoa including Acanthamoeba.

Yeasts in Internal Roots of the Rare Plant Dendropanax morbifera

  • Kim, Jong-Shik;Kim, Dae-Shin;Ko, Suk-Hyung
    • Journal of the Korean Applied Science and Technology
    • /
    • v.34 no.1
    • /
    • pp.33-40
    • /
    • 2017
  • To isolate and identify the yeast strains associated with D. morbifera, homogenized D. morbifera root samples were spread onto GPY, DG18, SCG and DOB agar media containing antibiotics, Triton X-100, and l-sorbose. Total 81 yeast isolates were analyzed by sequencing of internal transcribed spacer (ITS) region of the ribosomal DNA. The results showed that the root-associated yeast species were composed of the genera Vanderwaltozyma (40 isolates), Cryptococcus (40 isolates), and Kluyveromyces (one isolate). Moreover, the Kluyveromyces isolate exhibited high bioethanol productivity. In addition, the Vanderwaltozyma and Cryptococcus were dominant in D. morbifera roots. The specific yeast community associated with D. morbifera roots was identified by phylogenetic sequence analyses. These yeast isolates may have industrial applications as biosurfactant and bioethanol.

Isolation and Characterization of Two Amino Acid-activating Domains of Peptide Synthetase Gene from Bacillus subtilis 713

  • Lee, Youl-Soon;You, Sang-Bae;Lee, Ji-Wan;Kim, Tae-Young;Kim, Sung-Uk;Bok, Song-Hae
    • Journal of Microbiology and Biotechnology
    • /
    • v.8 no.4
    • /
    • pp.399-405
    • /
    • 1998
  • From the sequence alignment of various non-ribosomal peptide synthetases, several motifs of highly conserved sequences have been identified within each domain of peptide synthetases. We designed PCR primers based on the highly conserved nucleotide sequences to amplify and isolate a ∼7.2-kb DNA fragment of the Bacillus subtilis 713 which was isolated and reported to produce an antifungal peptide compound. Nucleotide sequence analysis of 4.8 kb of the predicted amino acids revealed significant homology to various peptide synthetases over the whole sequence and also revealed two amino acid-activating domains with highly conserved Core 1 to Core 6 and spacer motif. This suggests that the isolated DNA fragment is part of a peptide synthetase gene for antifungal peptide.

  • PDF

Aural Abscess in a River Cooter (Pseudemys concinna)

  • Bae, Jieun;Go, Jae Cheon;Son, Jiwon;Han, Jae-Ik
    • Journal of Veterinary Clinics
    • /
    • v.37 no.1
    • /
    • pp.57-59
    • /
    • 2020
  • A 3-year-old, captive female river cooter was presented with a 4-day history of progressive unilateral swelling of the right side of the head, lethargy, and anorexia. History, physical examination, and radiographic examination revealed an aural abscess. After administration of antibiotics and supportive care, surgical intervention was performed. Swab samples were collected from the tympanic cavity during surgery for cytology and antimicrobial susceptibility testing. Molecular analyses of 16S ribosomal RNA gene sequences identified Citrobacter spp. and Morganella morganii. The patient was treated with ciprofloxacin and meloxicam and recovered after 2 months. This report describes the successful correction of a unilateral aural abscess that responded well to surgical intervention and a properly selected antibiotic.

Maxillary Sinusitis by Staphylococcus aureus Infection in a Thoroughbred Gelding: Case Report

  • Lee, Sang Kyu;Lee, Inhyung
    • Journal of Veterinary Clinics
    • /
    • v.38 no.5
    • /
    • pp.225-230
    • /
    • 2021
  • A 4-year-old gelding Thoroughbred racehorse, which had been undergoing antibiotic therapy at a local veterinary clinic, was referred to the KRA veterinary center with a 20-day history of continuous right nasal discharge. Patient's history, endoscopic examination, and radiographic examination revealed primary maxillary sinusitis. Under sedation, surgical intervention was performed to collect samples and remove the accumulated mucopurulent exudate in the sinus. Swab samples were collected from the sinus during surgery for cytology and antimicrobial susceptibility testing. Only one type of bacteria was cultured, and molecular analyses of 16S ribosomal RNA gene sequences identified it as Staphylococcus aureus (S. aureus). The isolate was resistant to multiple antibiotics, which are frequently used in equine practice. Trimethoprim-sulfamethoxazole was chosen based on antibiotic susceptibility test, trephination, and sinus lavage using saline were applied to treat bacterial sinusitis. The clinical signs improved after 1 month and the patient resumed training. This report describes S. aureus isolated from bacterial maxillary sinusitis in a horse and its antibiotic susceptibility.