MW: 499.6 to 1038; log Kow -1.0 to 3.2; Henry's Law constant: negligible to 2.8X10-23 Pa-L/mol (Polypeptides e.g. avermectin, bacitracin, ivermectin, virginamycin)
Reduction of virginiamycin S with sodium borohydride produces allo- & normal-dihydro-virginiamycin S. Reduction of the tosylhydrazone of virginiamycin S with sodium cyanoborohydride affords deoxyvirginiamycin S. These compounds are less active than virginiamycin S. Like virginiamycin S they enhance the activity of virginiamycin M1.
Virginiae butanolides (VBs), which are among the butyrolactone autoregulators of Streptomyces species, act as a primary signal in Streptomyces virginiae to trigger virginiamycin biosynthesis & possess a specific binding protein, BarA. To clarify the in vivo function of BarA in the VB-mediated signal pathway that leads to virginiamycin biosynthesis, two barA mutant strains (strains NH1 & NH2) were created by homologous recombination. In strain NH1, an internal 99-bp EcoT14I fragment of barA was deleted, resulting in an in-frame deletion of 33 amino acid residues, including the second helix of the probable helix-turn-helix DNA-binding motif. With the same growth rate as wild-type S. virginiae on both solid & liquid media, strain NH1 showed no apparent changes in its morphological behavior, indicating that the VB-BarA pathway does not participate in morphological control in S. virginiae. In contrast, virginiamycin production started 6 hr earlier in strain NH1 than in the wild-type strain, demonstrating for the first time that BarA is actively engaged in the control of virginiamycin production & implying that BarA acts as a repressor in virginiamycin biosynthesis. In strain NH2, an internal EcoNI-SmaI fragment of barA was replaced with a divergently oriented neomycin resistance gene cassette, resulting in the C-terminally truncated BarA retaining the intact helix-turn-helix motif. In strain NH2 & in a plasmid-integrated strain containing both intact & mutated barA genes, virginiamycin production was abolished irrespective of the presence of VB, suggesting that the mutated BarA retaining the intact DNA-binding motif was dominant over the wild-type BarA. These results further support the hypothesis that BarA works as a repressor in virginiamycin production & suggests that the helix-turn-helix motif is essential to its function. In strain NH1, VB production was also abolished, thus indicating that BarA is a pleiotropic regulatory protein controlling not only virginiamycin production but also autoregulator biosynthesis.
Previous findings suggest the location of the central loop of domain V of 23S rRNA within the peptidyltransferase domain of ribosomes. This enzymatic activity is inhibited by some antibiotics, including type A (virginiamycin M or VM) & type B (virginiamycin S or VS) synergimycins, antibiotics endowed with a synergistic action in vivo. In the present work, the ability of VM & VS to modify the accessibility of 23S rRNA bases within ribosomes to chemical reagents has been explored. VM afforded a protection of rRNA bases A2037, A2042, G2049 & C2050. Moreover, when ribosomes were incubated with the two virginiamycin components, the base A2062, which was protected by VS alone, became accessible to dimethyl sulphate (DMS). Modified reactivity to chemical reagents of different rRNA bases located either in the central loop of domain V or in its proximity furnishes experimental evidence for conformational ribosome alterations induced by VM binding
Emergency and supportive measures: Maintain an open airway and assist ventilation if necessary. Treat coma, seizures, hypotension, anaphylaxis, and hemolysis if they occur. Replace fluid losses resulting from gastroenteritis with intravenous crystalloids. /Antibacterial agents/
来源:Hazardous Substances Data Bank (HSDB)
毒理性
解毒与急救
去污：如果条件适当，口服活性炭。如果可以迅速给予活性炭，小型到中型的摄入后不需要洗胃。/抗菌剂/
Decontamination: Administer activated charcoal orally if conditions are appropriate. Gastric lavage is not necessary after small to moderate ingestions if activated charcoal can be given promptly. /Antibacterial agents/
Enhanced elimination: Most antibiotics are excreted unchanged in the urine, so maintenance of adequate urine flow is important. The role of forced diuresis is unclear. Hemodialysis is not usually indicated, except perhaps in patients with renal dysfunction and a high level of a toxic agent. /Antibacterial agents/
/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/
/CASE REPORTS/ Four cases of eczematous-like drug eruption after oral ingestion of synergistins, pristinamycin (3 cases) & virginiamycin (1 case) /are reported/. The lesions occurred after contact sensitization with topical virginiamycin. The clinical symptoms appeared a few hours after ingestion: a generalized maculopapular eruption, sometimes with general symptoms of anaphylactic reaction. Eczema appeared again on initial areas of contact dermatitis. There is a common allergenic group between these 2 antibiotics, which is a macrocyclic lactone. Physiopathology of this drug eruption is not clear: allergic reaction of the delayed type or anaphylactic reaction. Patients allergic to virginiamycin should be strongly cautioned against oral pristinamycin.
The results of residue determinations of the growth promotors carbadox, tylosin, & virginiamycin in kidney, liver, & muscle from pigs in feeding experiments are described as well as the analytical methods used. Residues of the carbadox metabolite quinoxaline-2-carboxylic acid were found in liver from pigs fed 20 mg/kg in the diet with a withdrawal time of 30 days. No residues were detected in muscle with zero withdrawal time. The limit of determination was 0.01 mg/kg for both tissues. No residues of virginiamycin & tylosin were found in pigs fed 50 & 40 mg/kg, respectively, in the diet, even with zero withdrawal time. Residues of tylosin of 0.06 mg/kg & below were detected in liver & kidney from pigs fed 200 or 400 mg/kg & slaughtered within 3 h after the last feeding.
