Examination of the mechanisms of antibiotic resistance of strains of Mycoplasma fermentans, Mycoplasma hominis, Mycoplasma laidlawii, Mycoplasma orale II, Mycoplasma pharyngis, Mycoplasma salivarium and selected species of avian Mycoplasma to chloramphenicol, dihydrostreptomycin, and tetracycline showed that in the cultures studied, reduced antibiotic uptake was involved rather than specific degradation of the antibiotic.
Enduracidin (enramycin) was found to have high order of antibacterial activity against various antibiotic-resistant strains of staphylococci, and to be free of cross-resistance with antibiotics commercially available at present. This drug was proved to be ineffective against dysentery bacillus and other gram-negative bacilli. It is believed to be an agent to which bacterial resistance hardly increases. The 50% effective dose (ED50) of enramycin in experimental Staphylococcus aureus infections in mice was proved to be 2.27 mg/kg.
ATP-dependent DNA ligase prepared from ascites hepatoma of rat was markedly inhibited by bleomycin at the low concentration. The inhibition was observed in the absence of a thiol compound. However, the degree of inhibition was increased by addition of mercaptoethanol to the reaction mixture. The principal mechanism of inhibition was found to involve the strand scission of DNA which was not repaired by the ligase. The inhibition at rather low concentration of bleomycin suggested that this antibiotic might affect the joining of DNA by binding to DNA strand or by interaction with the enzyme.
The effects of yemenimycin on the growth and contents of DNA, RNA and proteins of Candida albicans were appraised. Glycolysis and aerobic respiration were less sensetive to the antibiotic than the syntheses of nucleic acids and proteins. Incorporation of P-32 in DNA and RNA was markedly arrested by yemenimycin whereas the contents of the labeled supplement in TCA soluble fraction and phospholipids were appreciably augmented. Yemenimycin restricted the incorporation of C14-thymidine and to a lesser extent of C14-uridine in Bacillus subtilis cells while the incorporation of H3-lysine in cellular protein was relatively the most resistant. Synthesis of aminoacyltRNA and the binding of C14-phenylalanyl-tRNA to ribosomes in response to poly U were found to be rather insensitive to the drug. Finally the effect of yemenimycin on the protein synthesis of intact rabbit reticulocytes and their cell-free system was assessed. The antibiotic could influence unfavorably the synthesis of protein.
A strain of Streptomyces, designated as No. 2-89, newly isolated from a soil sample was very closely related in its cultural and morphological characteristics to variant strains of Streptomyces phaeoverticillatus which originally produced iyomycins. This strain was named as S. phaeoverticillatus var. takatsukiensis after the location, Takatsuki-shi, Osaka, Japan, where the soil sample yielding the strain No. 2-89 was collected. Whenthe strain of S. phaeoverticillatus var. takatsukiensis was fermented in the culture medium containing an anthraquinone sulfonate compound, a new antimicrobial and antitumor antibiotic named kidamycin, was produced. Kidamycin was obtained as orange red crystals, and differed from iyomycin B1 by its toxicity, melting point, and infrared absorption spectrum. The taxonomy of the strains, fermentation, isolation, and physico-chemical and biological properties of kidamycin were investigated.
Disodium α-sulfobenzylpenicillin (sulfocillin) shows a potent in vitro antibacterial activity against Gram-positive and Gram-negative bacteria. In vitro studies of sulfocillin were carried out using the microorganisms lately isolated from clinical source. Sulfocillin demonstrates antibacterial activity against penicillin G resistant strains of staphylococci as nearly strong as that against the sensitive ones. Against Escherichia coli, Proteus vulgaris and P. mirabilis, sulfocillin is also active, while being moderate against P. morgani and Pseudomonas aeruginosa. The antibacterial activity is somewhat influenced by the inoculum size, being strong in the case of a small inoculum at acidic pH. The activity is influenced neither by the presence of horse serum in the medium, nor by the difference of test media. Protein binding rate of the penicillin examined by cellophane bag dialysis is low. Sulfocillin is relativelystable against staphylococcal penicillinase. Bacterial resistance to sulfocillin is demonstrated stepwise by the serial transfer, as in the case of carbenicillin. Cross resistance is found between sulfocillin and other penicillins against Staphylococcus aureus FDA 209P and Escherichia coli NIHJ JC-1, which are made resistant to penicillins by serial subcultures in culture medium. Bactericidal and bacteriolytic examinations with S. aureus FDA 2O9P and E. coli NIHJ JC-1 reveals strong activities of sulfocillin. The paradoxical reduction of both activities at high concentrations of sulfocillin and carbenicillin was observed with S. aureus FDA 209P. Sulfocillin is relatively stable at pH 2.
The therapeutic activities of a new semi-synthetic penicillin, disodium α-asulfobenzylpenicillin (sulfocillin) in comparison with carbenicillin were studied in mice infected intraperitoneally with either Staphylococcus aureus (benzylpenicillin sensitive as well as resistant strains), Streptococcus pyogenes, Diplococcus pneumoniae, Pseudomonas aeruginosa, Escherichia coli, Proteus vulgaris or Klebsiella pneumoniae. Both sulfocillin and carbenicillin were more effective by the parenteral route than by the oral route. Sulfocillin proved to be more effective than carbenicillin in the mice challenged with D. pneumoniae and P. aeruginosa when both penicillins were given three times after infection, while their effects by the single dose on the animals challenged with other microorganisms such as benzylpenicillin-sensitive S. aureus, S. pyogenes and K. pneumoniae were comparable. Sulfocillin was equieffective in the treatment of the animals infected with benzylpenicillin resistant or sensitive strains of S. aureus, whereas carbenicillin was somewhat less effective against the resistant strain.
The syntheses and antibacterial activities of various sterically hindered penicillins from 2-aryl-3-methylcrotonic acids (la), 2-aryl-3-azidomethylisocrotonic acid (1b) and 2-aryl-3-aminomethylisocrotonic acids (lc) are reported. Although the penicillins la and lb show good activity against Gram-positive microorganisms, they are only effective against penicillinase-producing strains of Staphylococcus aureus at small inocula. The aminopenicillins lc exhibit broad-spectrum activity and are not appreciably serum-bound. The presence of the amino group has resulted in increased penicillinase resistance and a 4-50 fold increase in Gram-negative activity.
Coriolus consors was cultured under aeration, and from the mycelial cake coriolin B, a sesquiterpene compound, was extracted and purified. Coriolin B showed no antimicrobial activity. However diketocoriolin B which was obtained by the oxidation of coriolin B showed antibacterial and antitumor activities. Diketocoriolin B prolonged the survival period of mice inoculated intraperitoneally with mouse leukemia L-1210 cells or Ehrlich carcinoma cells.
Two prodigiosin-like pigments from Actinomadura pelletieri were shown to be undecylprodiginine (III) and methylcyclodecylprodiginine (VI). The antimicrobial activity of four prodiginine pigments is given.
When ampicillin was injected into a healthy volunteer and experimental animals, an unknown substance with an antimicrobial activity was recovered in the urine together with unchanged ampicillin. This unknown substance was also formed when ampicillin was incubated with urine, serum or homogenate of rat tissues. The causative agent responsible for this new transformation product seemed to be of low molecular weight and stable to heat. This transformation product showed a lower antimicrobial activity than ampicillin against some gram-negative bacteria. The concentrations of this product in the serum and urine of a healthy volunteer receiving ampicillin intramuscularly were far lower than those of ampicillin.