Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “FUSIDIC ACID”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 811 records · Page 45Linked to original sources
PubMed1970

Binding of adenosine 3':5'-cyclic phosphate to G factor of Escherichia coli, and its effects on GTPase, RNase V, and protein synthesis.

Unique among adenine nucleotides tested by filter binding assays, 3':5'-cyclic AMP binds to the G translocation factor. Binding is dependent on the presence of GTP, and is inhibited by GDP, by the analog 5'-beta,gamma-methylene GTP, and by the antibiotic fusidic acid. The cAMP seems to be released during the ribosome-dependent translocation of charged tRNA catalyzed by G factor. Bound cAMP inhibits GTPase and ribosome-associated degradation of messenger RNA, but does not inhibit protein synthesis. cAMP might thereby regulate the ratio of productive to degradative transits of ribosomes on messenger RNA, and this may account for some part of its profound effect on levels of specific bacterial messenger RNA species.

Adenine Nucleotides↗
PubMed1972

Inhibition by elongation factor EF G of aminoacyl-tRNA binding to ribosomes.

Elongation factor G (EF G), bound to ribosomes either with GMPPCP or with fusidic acid and GDP, inhibits elongation factor Tu (EF Tu)-dependent binding of Phe-tRNA on the ribosome-poly(U) complex and binding of Ala-tRNA on the initiation complex formed with RNA from bacteriophage R17; GTP hydrolysis associated with Phe-tRNA binding is also inhibited. Moreover, nonenzymic binding of Phe-tRNA at high Mg(++) concentration is completely blocked by EF G. Thus, EF G appears to bind at a site that overlaps or interacts with the ribosomal A-site.

Amino Acids↗
PubMed1972

Elongation factors EF Tu and EF G interact at related sites on ribosomes.

The binding of elongation factor EF G to ribosomes inhibits the subsequent reaction of the ribosomes with the ternary complex aminoacyl-tRNA.EF Tu.GTP. Both the hydrolysis of GTP and the binding of aminoacyl-tRNA to ribosomes are nearly abolished by the previous binding of factor EF G to ribosomes in the presence of either fusidic acid plus either GTP or a nonhydrolyzable analog of GTP. The results suggest that each elongation factor binds to the same region on the ribosome. The GTPase activities of both factors EF G and EF Tu may be activated by interaction at the same ribosomal site, as has been previously suggested by others.

Escherichia coli↗
PubMed1972

Formation of a mammalian initiation complex with reovirus messenger RNA, methionyl-tRNA F , and ribosomal subunits.

Previous data demonstrated that reovirus mRNA, synthesized in vitro with the particulate RNA transcriptase of reovirus cores, efficiently directs the synthesis of polypeptides in vitro. The present studies indicate that all of the three size classes of reovirus mRNA produced in vitro can form protein initiation complexes with rat liver [(36)S]Met-tRNA(F) and incubated 40S and 60S ribosomal subunits, which had been washed in 0.5 M KCl of mouse fibroblast L-929 cells. Mild prior treatment of the mRNA with HCHO was required to expose the initiator region. The initiation complex reacted quantitatively with puromycin to form a puromycin peptide, whose electrophoretic properties were identical to methionyl-puromycin formed in response to poly(A,G,U) or the initiator codon AUG. The complex was relatively stable and specific for [(35)S]Met-tRNA(F); rat liver [(35)S]Met-tRNA(M) was unreactive unless the supernatant factors EF T(1) and EF T(2) were also present. However, the addition of fusidic acid, at a concentration that did not affect complex formation with [(35)S]Met-tRNA(F), completely inhibited Met-tRNA(M) utilization. Exogenous ribosomal factors and GTP were not required unless the separated 40S and 60S subunits were further treated with 1 M KCl. The data suggest that reovirus mRNA contains AUG initiator codons that form a complex with Met-tRNA(F) at a puromycin-reactive site on ribosomes.

Animals↗
PubMed1972

Expression of ribosomal protein genes as analyzed by bacteriophage Mu-induced mutations.

The organization of ribosomal protein genes and the gene (fus) for a protein chain elongation factor, EF G, in Escherichia coli were studied with a merodiploid strain that has an episome with genetic markers, ery(r), spc(r), str(r), and fus(r), and a chromosome with markers ery(s), spc(s), str(s), and fus(s). The ery locus determines a 50S ribosomal protein and the spc and str loci determine 30S ribosomal proteins. The phenotype of the diploid strain is sensitive to all of the four antibiotics, erythromycin (Ery), spectinomycin (Spc), streptomycin (Str), and fusidic acid (Fus). Analysis of antibiotic-resistant mutants induced by bacteriophage Mu in the diploid strain indicates that these four genes, and probably many other ribosomal protein genes linked to them, are transcribed as a single unit, and the direction of the transcription is in the order of ery, spc, str, and fus.

Bacterial Proteins↗
PubMed1998

Visualization of elongation factor G on the Escherichia coli 70S ribosome: the mechanism of translocation.

During protein synthesis, elongation factor G (EF-G) binds to the ribosome and promotes the step of translocation, a process in which tRNA moves from the A to the P site of the ribosome and the mRNA is advanced by one codon. By using three-dimensional cryo-electron microscopy, we have visualized EF-G in a ribosome-EF-G-GDP-fusidic acid complex. Fitting the crystal structure of EF-G-GDP into the cryo density map reveals a large conformational change mainly associated with domain IV, the domain that mimics the shape of the anticodon arm of the tRNA in the structurally homologous ternary complex of Phe-tRNAPhe, EF-Tu, and a GTP analog. The tip portion of this domain is found in a position that overlaps the anticodon arm of the A-site tRNA, whose position in the ribosome is known from a study of the pretranslocational complex, implying that EF-G displaces the A-site tRNA to the P site by physical interaction with the anticodon arm.

Crystallography, X-Ray↗
PubMed2003

Identification and characterization of a novel translational repressor of the steroid-inducible 3 alpha-hydroxysteroid dehydrogenase/carbonyl reductase gene in Comamonas testosteroni.

Comamonas testosteroni 3 alpha-hydroxysteroid dehydrogenase/carbonyl reductase (3 alpha-HSD/CR) is a key enzyme in the degradation of steroid compounds in soil and may therefore play a significant role in the bioremediation of hormonally active compounds in the environment. The enzyme is also involved in the degradation of the steroid antibiotic fusidic acid. In addition, 3 alpha-HSD/CR mediates the carbonyl reduction of non-steroidal aldehydes and ketones. Because the gene of 3 alpha-HSD/CR (hsdA) is inducible by steroids, we were interested in the mode of its molecular regulation. Recently, we could identify the first molecular determinant in procaryotic steroid signaling, i.e. a repressor protein (RepA), which acts as a negative regulator by binding to upstream operator sequences of hsdA, thereby blocking hsdA transcription. In this work, we identified and cloned a second novel regulator gene that we named repB. The gene locates 932 bp downstream from hsdA on the C. testosteroni chromosome with an orientation opposite to that of hsdA. The open reading frame of repB consists of 237 bp and translates into a protein of 78 amino acids that was found to act as a repressor that regulates hsdA expression on the translational level. Northern blot analysis, UV-cross linking, gel-shift assays, and competition experiments proved that RepB binds to a 16-nucleotide sequence downstream of AUG at the 5' end of the 3 alpha-HSD/CR mRNA, thereby blocking hsdA translation. Testosterone, on the other hand, was shown to specifically bind to RepB, thereby yielding the release of RepB from the 3 alpha-HSD/CR mRNA such that hsdA translation could proceed. Data bank searches with the RepB primary structure yielded a 46.2% identity to the regulator of nucleoside diphosphate kinase, a formerly unknown protein from Escherichia coli that can restore a growth defect in alginate production in Pseudomonas aeruginosa. In conclusion, the induction of hsdA by steroids in fact is a derepression where steroidal inducers bind to two repressor proteins, RepA and RepB, thereby preventing blocking of hsdA transcription and translation, respectively.

Alcohol Oxidoreductases↗
PubMed2004

High antibiotic susceptibility among bacterial pathogens in Swedish ICUs. Report from a nation-wide surveillance program using TA90 as a novel index of susceptibility.

Local infection control measures, antibiotic consumption and patient demographics from 1999-2000 together with bacteriological analyses were investigated in 29 ICUs participating in the ICU-STRAMA programme. The median antibiotic consumption per ICU was 1147 (range 605-2143) daily doses per 1000 occupied bed d (DDD1000). Antibiotics to which > 90% of isolates of an organism were susceptible were defined as treatment alternatives (TA90). The mean number of TA90 was low (1-2 per organism) for Enterococcus faecium (vancomycin:VAN), coagulase negative staphylococci (VAN), Pseudomonas aeruginosa (ceftazidime:CTZ, netilmicin: NET) and Stenotrophomonas maltophilia (CTZ, trimethoprim-sulfamethoxazole: TSU), but higher (3-7) for Acinetobacter spp. (imipenem:IMI, NET, TSU), Enterococcus faecalis (ampicillin:AMP, IMI, VAN), Serratia spp. (ciprofloxacin:CIP, IMI, NET), Enterobacter spp. (CIP, IMI, NET, TSU), E. coli (cefuroxime:CXM, cefotaxime/eftazidime:CTX/CTZ, CIP, IMI, NET, piperacillin-tazobactam:PTZ, TSU), Klebsiella spp. (CTX/CTZ CIP, IMI, NET, PTZ, TSU) and Staphylococcus aureus (clindamycin, fusidic acid, NET, oxacillin, rifampicin, VAN). Of S. aureus isolates 2% were MRSA. Facilities for alcohol hand disinfection at each bed were available in 96% of the ICUs. The numbers of TA90 available were apparently higher than in ICUs in southern Europe and the US, despite a relatively high antibiotic consumption. This may be due to a moderate ecological impact of the used agents and the infection control routines in Swedish ICUs.

Adult↗
PubMed1986

Improved method for estimation of azole antifungal inhibitory concentrations against Candida species, based on azole/antibiotic interactions.

Low, reproducible minimal inhibitory concentrations against Candida species, with sharp, precise end points in complex media were achieved for imidazoles (clotrimazole, econazole, miconazole, tioconazole and ketoconazole) and triazoles (fluconazole, itraconazole, vibunazole, ICI 153066) by including in the test medium antibacterial antibiotics that bind to the 80S eukaryotic ribosome and inhibit protein synthesis, i.e. blasticidin, cycloheximide, doxycycline, neomycin and gentamicin. The presence of these antibiotics reduced MICs, on average, by 50- to 250-fold. Other protein synthesis inhibitors (rifampicin, erythromycin, lincomycin, clindamycin, chloramphenicol and fusidic acid) were not effective, and the antibiotics did not affect MICs for Aspergillus species. The low azole MICs were in close agreement with MICs obtained in a defined, tissue culture-based medium lacking added antibiotics.

Anti-Bacterial Agents↗
PubMed1998

Local application of honey for treatment of neonatal postoperative wound infection.

Honey has been described in ancient and modern medicine as being effective in the healing of various infected wounds. In this report we present our experience in nine infants with large, open, infected wounds that failed to heal with conventional treatment. Conventional treatment was defined as having failed if after > or = 14 d of intravenous antibiotic and cleaning the wound with chlorhexidine 0.05% W/V in aqueous solution and fusidic acid ointment the wound was still open, oozing pus, and swab cultures were positive. All infants showed marked clinical improvement after 5 d of treatment with topical application of 5-10 ml of fresh unprocessed honey twice daily. The wounds were closed, clean and sterile in all infants after 21 d of honey application. There were no adverse reactions to the treatment. We conclude that honey is useful in the treatment of post-surgical wounds that are infected and do not respond to conventional systemic and local antibiotic treatment.

Honey↗
PubMed2002

Relationships between molecular properties and antimycobacterial activities of steroids.

Progesterone (1), cholesterol (2), stigmasterol (3), ergosterol endoperoxide (4), sitosterol (5), betulin (6), fusidic acid (7), chondrilasterol (8), and ergosterol (9) have been evaluated against Mycobacterium tuberculosis H37Rv. The maximum antimycobacterial activity seemed to depend on hydrophobicity and the type of substituents on the phytyl moiety on steroidal backbone. The variation in activity was rationalized using quantitative structure-activity relationship (QSAR) models based on several molecular descriptors including van der Waals surface area (VDW(A)), van der Waals volume (VDW(v)), polarizability, dipole moment, logP, and the differences between the Highest Occupied Molecular Orbital and the Lowest Unoccupied Molecular Orbital (HOMO-LUMO gap). The proposed QSAR models could be developed to predict the antimycobacterial activity of structurally similar steroids and to create a priority list for testing so that time, money, and effort can be focused on the potentially most promising steroids. The implications of QSAR data for the rational design of new antituberculosis agents are discussed. Because mycobacteria degrade steroids to progesterone-type compounds, unambiguous assignments of the high-field proton (1H) and carbon-13 (13C) NMR data of progesterone (1) were achieved through a combination of modern one- and two-dimensional (2D) NMR techniques.

Antitubercular Agents↗
PubMed1974

Production of membrane whorls in rat liver by some inhibitors of protein synthesis.

Inhibitors of protein synthesis capable of differential effects on nascent peptide synthesis on membrane-bound and free polyribosomes were employed to investigate the structure and function of cellular membranes of liver. The formation of membranous whorls in the cytoplasm and distension of nuclear membranes were induced by inhibitors of protein synthesis (i.e., cycloheximide and emetine) which predominantly interfere with nascent peptide synthesis on membrane-bound polyribosomes in situ. Other inhibitors of protein synthesis such as puromycin and fusidic acid, which inhibit nascent peptide synthesis on both free and membrane-bound polyribosomes, and chloramphenicol, which inhibits mitochondrial protein synthesis, did not induce these alterations. Cycloheximide, puromycin, and chloramphenicol produce some common cellular lesions as reflected by similar alterations in morphology, such as swelling of mitochondria, degranulation of rough endoplasmic reticulum, and aggregation of free ribosomes. The process of whorl formation in the cytoplasm, the incorporation of [(3)H]leucine and of [(3)H]choline into endoplasmic reticulum and the total NADPH-cytochrome c reductase activity of the endoplasmic reticulum were determined. During maximum formation of membranous whorls, [(3)H]leucine incorporation into cytoplasmic membranes was inhibited, while [(3)H]choline incorporation into these structures was increased; maximum inhibition of protein synthesis and stimulation of choline incorporation into endoplasmic reticulum, however, preceded whorl formation. Cycloheximide decreased the activity of NADPH-cytochrome c reductase of rough endoplasmic reticulum, but increased NADPH-cytochrome c reductase activity of smooth endoplasmic reticulum. In addition, cycloheximide decreased the content of hemoprotein in both the microsomal and mitochondrial fractions of rat liver, and the activities of mixed function oxidase and of oxidative phosphorylation were impaired to different degrees. Succinate-stimulated microsomal oxidation was also inhibited. The possible mechanisms involved in the formation of membranous whorls, as well as their functions, are discussed.

Animals↗
PubMed2005

Spread of clones of multidrug-resistant, coagulase-negative staphylococci within a university hospital.

OBJECTIVE: To detect putative clonal dissemination of multidrug-resistant, coagulase-negative staphylococci (CNS) in a university hospital in northern Sweden. METHODS: All consecutive routine clinical samples from our hospital were screened during two periods (November and December 2001 and September and October 2002) for the presence of multidrug-resistant (defined as resistant to oxacillin, clindamycin, co-trimoxazole, gentamicin, and fusidic acid, but susceptible to vancomycin) isolates of CNS. Genetic similarity between isolates was analyzed using pulsed-field gel electrophoresis (PFGE) and a computer program. RESULTS: Seventy multidrug-resistant isolates from 62 patients were identified, 28 during the 2001 period and 42 during the 2002 period. All isolates except one, which was Staphylococcus haemolyticus, were identified as S. epidermidis. Multidrug-resistant CNS were isolated in samples obtained from 24 different wards. Two subgroups (group A and group B) of S. epidermidis that differed by approximately 40% in PFGE band similarity were identified. Group A consisted of 44 isolates with a PFGE band similarity of greater than 70% that included 6 subgroups consisting of 3 to 16 isolates that expressed a 100% similarity. These isolates were identified during both sampling periods in cultures performed in 18 different wards. A clonal origin could not be excluded for some of the remaining 26 isolates belonging to group B, but none had identical PFGE patterns, suggesting a more diverse origin. CONCLUSION: The results of this study suggest clonal spread of multidrug-resistant CNS within our hospital and that some clones are endemic in the hospital environment.

Adolescent↗
PubMed2004

An international multicenter study of antimicrobial resistance and typing of hospital Staphylococcus aureus isolates from 21 laboratories in 19 countries or states.

During 1996, 4065 consecutive Staphylococcus aureus strains from different patients were collected in 21 worldwide hospital laboratories. The strains, their resistance pattern, and hospital demographic data were forwarded to Statens Serum Institut where the strains were typed and data analyzed. Resistance patterns varied by region and resistance to other antibiotics than methicillin were mainly related to the occurrence of methicillin resistance, except for mupirocin, rifampicin, and fusidic acid. Methicillin-resistant S. aureus (MRSA) occurred with low levels in hospitals in Northern Europe (<1%), increasing levels in middle-European countries, United States, New Zealand, and Australia (6-22%), and very high levels in Southern European countries as well as in parts of the United States, Asia, and South Africa (28-63%). MRSA found in large hospitals were more resistant to other antibiotics than MRSA found in smaller hospitals serviced by the same laboratory. No difference in resistance levels was seen for methicillin-susceptible S. aureus (MSSA) isolated in large or small hospitals. Intensive Care Units had the highest level of MRSA. Strains from the lower respiratory tract showed the highest resistance levels and blood isolates the lowest. A dominating MRSA clone was found in hospitals with an MRSA frequency of more than 10%. Pulsed-field gel electrophoresis (PFGE) typing recognized several of these clones as international epidemic MRSA (E-MRSA). All MSSA isolates were phage typed (typeability 85.4%) and divided in seven major phage patterns. Isolates of all patterns were found in all hospitals except one, indicating that the MSSA seldom represented the spread of clones within the hospital. The comparison should evaluate the prevalence of community-acquired MRSA and identify internationally E-MRSA. The present study gives a snapshot of the MRSA situation, but it is important to build up a continuous national and international surveillance, because MRSA is a global socioeconomic problem. Global infection control procedures, including rational antibiotic use, should be agreed on. The accompanying paper will address the issue of antibiotic consumption and MRSA.

Africa↗
PubMed1989

Inhibition of bacterially expressed HIV protease activity determined by an in vitro cleavage assay with MuLV Pr65gag.

HIV protease is a virally coded enzyme that cleaves gag as well as gag-pol precursor polyproteins into functional products needed for virus assembly. A pUC plasmid containing an HIV insert starting at the 5' end of the pol gene and ending just inside the intergrase coding sequence was expressed in E. coli. It provided an 11 kD gene product (protease) that specifically cleaved the Gazdar MuLV Pr65gag precursor into Pr40gag (p30 + p10) and Pr27gag (p15 + p12) intermediates, as well as lower molecular weight gag-encoded products. These were detected by immunoblotting with either MuLV anti-p30 or p12 sera. Using cleavage of MuLV Pr65gag as an assay system, pepstatin A, fusidic acid, and cerulenin were observed to inhibit HIV protease cleavage by greater than 50% at concentrations of 0.1, 0.2-0.5, and 0.5 mM, respectively.

Cloning, Molecular↗
PubMed1995

Epidemiology of penicillin resistant pneumococci in Iceland.

The prevalence of penicillin-resistant pneumococci (PRP) has been increasing, with the highest levels reported from countries with relatively unrestricted antimicrobial use. It has been low in northern Europe except Iceland, which is disconcerting as antimicrobial use in Iceland has been relatively restricted. This suggests that other factors may facilitate their spread. By studying their epidemiology and possible risk factors for carriage, we have attempted to explain their rapid spread in Iceland. The incidence of infections caused by PRP (as percentage of infections considered due to pneumococci) has increased from 0% in 1988 to 2.3% in 1989, 2.7% in 1990, 8.4% in 1991, 16.3% in 1992, and 19.8% in 1993. The infections have mainly affected 0- to 3-year-old children (71.4%), and the PRP belonged almost exclusively to serogroups 6, 19, and 23 (98.8%). Most were serotype 6B multiresistant (75%; resistant to penicillin (MIC = 1.0), cephalothin, erythromycin, clindamycin, tetracycline, chloramphenicol, fusidic acid, sulfonamides, and trimethoprim), and believed to belong to a single clone originating from Spain. The PRP have been prevalent in healthy children, 0-10% nasopharyngeal carriage, especially in day-care centers, with the highest prevalence in areas that had the highest antimicrobial consumption. Recent antimicrobial consumption, especially of trimethoprim-sulfa, appeared to increase PRP carriage. The rapid spread of PRP in Iceland may have been facilitated by high antimicrobial consumption in day-care centers (especially of trimethoprim-sulfa) which are attended by the majority of Icelandic children.

Humans↗
PubMed1998

Spread of the multiresistant Iberian clone of methicillin-resistant Staphylococcus aureus (MRSA) to Italy and Scotland.

The multidrug-resistant "Iberian" clone of methicillin-resistant Staphylococcus aureus (MRSA) was first identified on the basis of its unique DNA fingerprints as the strain responsible for the massive 1989 outbreak of MRSA disease in the hospital Princeps d'Espanya, Barcelona, Spain. Most Iberian MRSA carry a constitutive beta-lactamase. They are resistant to most beta-lactam antibiotics, macrolides, aminoglycosides, tetracycline, rifampin and ciprofloxacin and are susceptible to fosfomycin, fusidic acid, mupirocin, sulfamethoxazole/trimethoprim and vancomycin. The characteristic DNA fingerprints of the clone include the mecA polymorph I, Tn554 pattern E (or its variants), a chromosomal macrorestriction pattern (pulsed-field gel electrophoretic type) A (or its subtype variants), the lack of the mecI regulatory gene and a homogeneous, high level of expression of methicillin resistance. Molecular surveillance studies have documented the extensive spread of this clone to many Portuguese hospitals during the 1990s. In this article, we describe the spread of the Iberian MRSA to hospitals in Rome, Italy, and Scotland.

Anti-Bacterial Agents↗
PubMed2005

Emergence of rifampicin resistance in methicillin-resistant Staphylococcus aureus isolated at a Turkish university hospital.

Twenty-three rifampicin-resistant methicillin-resistant Staphylococcus aureus (MRSA) isolated in three wards at a university hospital in Turkey between June, 2000, and February, 2001, were studied for their genetic relatedness using a combination of antibiogram, coagulase serotyping, coagulase gene polymorphism (coa-RFLP), and pulsed-field gel electrophoresis (PFGE). They all expressed high-level rifampicin resistance (MIC, >256 mg/L) and were resistant to gentamicin, kanamycin, amikacin, ciprofloxacin, tetracycline, and cadmium acetate and were susceptible to fusidic acid, vancomycin, trimethoprim, and mupirocin. They belonged to the same coagulase serotype (serotype IV) and had identical coa-RFLP patterns. In contrast, PFGE generated nine banding patterns designated type A, types A1-A5, B, C, and D. The most common PFGE pattern (type A) and its subtypes (types A1-A5) were seen in 20 (87%) of the 23 isolates in the three wards. The results demonstrated the acquisition of rifampicin resistance by different MRSA clones and the spread of one clone among patients in the three wards.

Coagulase↗