Disease relevance of fusidic acid

• Fusidic acid resistance in Staphylococcus aureus isolates [1].
• These results justify fuller evaluation of fusidic acid as therapy against AIDS and HIV infection [2].
• Fusidic acid, HIV, and host cell toxicity [3].
• Delayed type hypersensitivity to fusidic acid in patients with chronic dermatitis [4].
• Granulocytopenia due to fusidic acid [5].

High impact information on fusidic acid

• Treatment of chronic endogenous uveitis with fusidic acid [6].
• Effect of bile salts and of fusidic acid on HIV-1 infection of cultured cells [7].
• In contrast, fusidic acid and a GTP analog that fix EF-G to the ribosome, allowing one round of tRNA translocation, inhibited mRNA but not tRNA release from the complex [8].
• This effect is suppressed if the rate of ribosome movement is reduced with fusidic acid [9].
• On the other hand, RRF did not bind to EF-G-ribosome complexes with fusidic acid, suggesting that EF-G stabilized by fusidic acid does not represent the natural post-termination complex [10].

Chemical compound and disease context of fusidic acid

• Study of various Gram-negative species revealed that P. testosteroni, Pseudomonas acidovorans, and Acinetobacter calcoaceticus showed higher outer membrane permeability to steroid probes and higher susceptibility to hydrophobic agents such as fusidic acid, novobiocin and crystal violet relative to S. typhimurium and Escherichia coli [11].
• FusB was overexpressed in Escherichia coli as a polyhistidine-tagged fusion product, and the purified protein shown to protect an in vitro staphylococcal translation system from inhibition by fusidic acid in a specific and dose-dependent fashion [12].
• Fusidic acid alone or in combination with vancomycin for therapy of experimental endocarditis due to methicillin-resistant Staphylococcus aureus [13].
• Antimicrobial MIC data were obtained for 96 strains of Staphylococcus haemolyticus and the following 11 antimicrobial agents: methicillin, gentamicin, rifampin, fusidic acid, ciprofloxacin, vancomycin, teicoplanin; three experimental glycopeptides, MDL 62,873, MDL 62,208, and MDL 62,224; and an experimental lipoglycopeptide, ramoplanin [14].
• Comparative study of mupirocin and oral co-trimoxazole plus topical fusidic acid in eradication of nasal carriage of methicillin-resistant Staphylococcus aureus [15].

Biological context of fusidic acid

• Here we report the cloning, sequencing and overexpression of a single gene (fusB) from plasmid pUB101 capable of conferring resistance to fusidic acid in S. aureus [12].
• In each case, introduction of the mutant fusA alleles on plasmids into the fusidic acid-susceptible S. aureus strain RN4220 caused a fusidic acid-resistant phenotype [16].
• In conclusion, fusidic acid-resistant EF-G mutations alter the level of ppGpp and break the normal relationship between growth rate and cell size at division [17].
• Sequence analysis of fusA revealed mutational changes that cause amino acid substitutions in 10 fusidic acid-resistant clinical S. aureus strains as well as in 10 fusidic acid-resistant S. aureus mutants isolated under fusidic acid selective pressure in vitro [16].
• In this study, we demonstrate that fusidic acid resistance in Staphylococcus aureus results from point mutations within the chromosomal fusA gene encoding EF-G [16].

Anatomical context of fusidic acid

• The effects of pure and micellar solutions of different bile salts on mucosal morphology have been investigated in rat jejunum using a closed-loop technique; the effects of an anionic dihydroxy steroid antibiotic, fusidic acid, have also been studied [18].
• Lack of activity of fusidic acid against human immunodeficiency virus in monocytes [19].
• The phytohemagglutinin response, as well as the mixed lymphocyte culture stimulation of spleen lymphocytes from mice given 500 mg of fusidic acid per kg daily for 1 week, were significantly inhibited [20].
• The effect of fusidic acid on the multiplication of human immunodeficiency virus in monocyte-derived macrophages was examined in in vitro cultures [19].
• Interaction of fusidic acid with lipid membranes: Implications to the mechanism of antibiotic activity [21].

Associations of fusidic acid with other chemical compounds

• In addition, it was sensitive to the inhibitor of the translation elongation factor EF-G fusidic acid, and was also strongly inhibited by the triazine dye Cibacron Blue F3GA (Ki = 0.3 microM), suggesting the existence of a site able to recognize nucleotides [22].
• In vitro studies compared the activities of ciprofloxacin, vancomycin, and fusidic acid against staphylococci, streptococci, and enterococci [23].
• Limited evidence suggests that mupirocin may be as effective as chlortetracycline, fusidic acid, neomycin and other antibacterial agents, but more controlled, comparative studies are needed [24].
• The mutant exhibited increased susceptibility to both erythromycin and fusidic acid which was lost in single-step revertants to vancomycin resistance [25].
• No particular PCR ribotype was associated with clindamycin or fusidic acid resistance [26].

Gene context of fusidic acid

• One of these disruption mutants (in bmeB, the mexB homolog) was more susceptible than the parental strain to certain cephems, polypeptide antibiotics, fusidic acid, novobiocin, and puromycin [27].
• Hybridization of Southern blots revealed that far1 was not located on the chromosome or plasmid content of a limited number of Australian, UK and Hong Kong fusidic acid-resistant isolates [28].
• Treatment with fusidic acid (a specific inhibitor of EF-2) inhibits hyphal elongation and induces hyperbranching in a manner which mimics the cot-3 phenotype, and also leads to a decrease in the abundance of the LMW isoform of COT1 [29].
• Effect of fusidic acid on the hepatic cytochrome P450 enzyme system [30].
• Effect of fusidic acid on interleukin-1 (IL-1)- and IL-6-induced pancreatic beta-cell functions in rats [31].

Analytical, diagnostic and therapeutic context of fusidic acid

• To confirm the importance of observed amino acid exchanges in EF-G for the generation of fusidic acid resistance in S. aureus, three mutant fusA alleles encoding EF-G derivatives with the exchanges P406L, H457Y and L461K were constructed by site-directed mutagenesis [16].
• IF2 prevents the binding of EF-G to the ribosome, as shown by Western blot analysis and fusidic acid-stabilized EF-G.GDP.ribosome complex formation [32].
• In 10 of these 11 patients, the resistant follow-up isolate(s) belonged to the same PCR ribotype as the susceptible day 1 isolate, confirming frequent emergence of resistance to fusidic acid during treatment [33].
• The survival time of allografts in mice receiving fusidic acid from the day of the transplantation until the grafts were rejected was 26.1 days compared with 14.5 days in untreated animals [20].
• In conclusion, culture positivity for C. difficile was common after both fusidic acid and metronidazole therapy and was associated with treatment failure or recurrence of CDAD [33].

References