bluuebunny/crossref_metadata_2025 huggingface dataset:
Cephamycins, a New Family of β-Lactam Antibiotics I. Production by Actinomycetes, Including
Streptomyces lactamdurans
sp. n
Authors: Stapley E. O. , Jackson M. , Hernandez S. , Zimmerman S. B. , Currie S. A. , Mochales S. , Mata J. M. , Woodruff H. B. , Hendlin D.
Published: June 2012

A number of actinomycetes isolated from soil were found to produce one or more members of a new family of antibiotics, the cephamycins, which are structurally related to cephalosporin C. The cephamycins were produced in submerged fermentation in a wide variety of media by one or more of eight different species of
Streptomyces
, including a newly described species,
S. lactamdurans
. These antibiotics exhibit antibacterial activity against a broad spectrum of bacteria which includes many that are resistant to the cephalosporins and penicillins.
Cephamycins, a New Family of β-Lactam Antibiotics II. Isolation and Chemical Characterization
Authors: Miller T. W. , Goegelman R. T. , Weston R. G. , Putter I. , Wolf F. J.
Published: June 2012

Cephamycins A and B were isolated from the same fermentation broth of various actinomycetes by adsorption and ion-exchange methods. The antibiotics were separated from each other by column chromatography on a dextran-based ion-exchange resin. Cephamycin C was isolated from a different fermentation broth by ion-exchange and gel-filtration methods. The chemical characteristics of these new antibiotics were determined.
Mechanisms and Spectrum of Streptomycin Resistance in a Natural Population of
Pseudomonas aeruginosa
Authors: Tseng Jui Teng , Bryan L. E. , Elzen H. M. Van Den
Published: June 2012

A survey of 200 strains of
Pseudomonas aeruginosa
isolated from clinical specimens was made in an attempt to correlate the spectrum of their streptomycin resistance and the mechanism of resistance. The strains can be classified into three groups, according to their level of resistance to streptomycin: susceptible, low-level resistant, and high-level resistant strains. The mechanism of resistance of high-level resistant strains is either an R factor-mediated inactivation of streptomycin by phosphorylation or streptomycin-resistant ribosomes. However, such high-level resistant strains comprised less than 10% of the total strains isolated; the majority of the strains resistant to streptomycin were of low-level resistance. The latter are associated with a diminished uptake of streptomycin, and no evidence of streptomycin inactivation, resistant ribosomes, or R factors could be detected. The most probable explanation of low-level resistance is reduced permeability to streptomycin. Modification of the growth medium used in uptake studies simultaneously affected strongly both streptomycin incorporation and the minimal inhibitory concentration of streptomycin.
Effect of Ribosomal Wash Factors on Inhibition by Chloramphenicol
Authors: Cameron Helen J. , Rogers Samuel J. , Julian Gordon R.
Published: June 2012

In vitro protein-synthesizing systems from
Escherichia coli
can be categorized as either chloramphenicol-sensitive or chloramphenicol-insensitive. The chloramphenicol-sensitive systems used in this study required the presence of factors removed from ribosomes with 1.0
m
NH
4
Cl when chromatographically purified ribosomes were used for amino acid incorporation. These ribosomal wash factors inhibited but did not eliminate amino acid incorporation in chloramphenicol-insensitive systems. For both systems, addition of increasing amounts of the ribosomal wash factors increased the sensitivity to chloramphenicol inhibition.
Pharmacokinetics of Carbenicillin in Neonates of Normal and Low Birth Weight
Authors: Morehead C. David , Shelton Sharon , Kusmiesz Helen , Nelson John D.
Published: June 2012

A single intramuscular dose of 100 mg carbenicillin/kg produced measured peak concentrations of approximately 150 to 175 μg/ml in newborn infants. The carbenicillin serum half-life of 1.0 hr in normal adults was prolonged to 2.7 hr in infants of normal birth weight and to 4.0 hr in babies of low birth weight in the first week of life. One-third of a dose administered to babies of low birth weight and two-thirds of that given to babies weighing over 2,500 g was excreted by the kidney in 12 hr. Postadministration 6-hr urinary carbenicillin concentrations averaged 1,399 μg/ml after an intramuscular dose of 50 mg/kg and 2,689 μg/ml after a 100 mg/kg injection. Although carbenicillin is excreted by both glomerular and tubular mechanisms in adults, serum half-life and urinary carbenicillin excretion correlated well with creatinine clearance. Recommendations for dosage of carbenicillin and intervals of administration in the neonatal period are made based upon mathematical predictions from pharmacokinetic data.
Cephamycins, a New Family of β-Lactam Antibiotics. III. In Vitro Studies
Authors: Miller A. Kathrine , Celozzi Evemarie , Pelak Barbara A. , Stapley Edward O. , Hendlin David
Published: June 2012

Cephamycins A, B, and C are naturally produced cephalosporin-type antibiotics. Although A and B were found to be more active than C against gram-positive organisms, they were not so active against such strains as are cephalosporin C or the semisynthetic antibiotics cephaloridine and cephalothin. Against gram-negative organisms, cephamycin C was more active than A or B and, in general, was as active as the cephalosporins. In addition, cephamycin C was active in vitro against clinically isolated strains resistant to the cephalosporins, such as
Proteus, Providencia
, and
Escherichia coli
. The in vitro antibacterial activity of cephamycin C, cephalothin, and cephaloridine is primarily bactericidal. A 10,000-fold increase in inoculum of a strain of
Proteus mirabilis
resulted in 200-fold or greater increases in minimal inhibitory and minimal bactericidal end points of cephalothin and cephaloridine, but only 10- and 16-fold increases, respectively, for cephamycin C. After 15 passages through antibiotic-containing broths, during which time a culture of
E. coli
showed an increase in minimal inhibitory concentrations of streptomycin of >1,000-fold, end points for cephamycin C increased 4-fold, for cephalothin, 1.5-to 6-fold, and for cephaloridine, 128-fold.
Silver Sulfadiazine: Interaction with Isolated Deoxyribonucleic Acid
Authors: Rosenkranz Herbert S. , Rosenkranz Samuel
Published: June 2012

Silver sulfadiazine (AgSu) was found to interact with
isolated
deoxyribonucleic acid (DNA) to form nondissociable complexes. These complexes differ in physical and chemical properties from those that are established when silver nitrate is added to DNA. The reaction between AgSu and DNA is visualized as occurring in two stages: (i) a weak and reversible interaction (intercalation) between DNA and the sulfadiazine moiety and (ii) a tight binding involving the silver atom. In the first stage, sodium sulfadiazine competes with AgSu for the DNA.
Uptake and Binding of
14
C-Ethambutol by Tubercle Bacilli and the Relation of Binding to Growth Inhibition
Authors: Beggs William H. , Auran Nancy E.
Published: June 2012

Studies were designed to characterize ethambutol uptake by
Mycobacterium tuberculosis
(H37Ra) and to relate uptake to the time-dependent, concentration-independent nature of growth inhibition by ethambutol. When cells grown aerated at 37 C in Sauton medium were exposed for 7 hr to 0.2, 0.5, 1.0, 2.5, and 5.0 μg of
14
C-ethambutol per ml, uptake increased with time and was a linear function of concentration. The process was inhibited at 22 C. Studies with chloramphenicol, sodium azide, and 2,4-dinitrophenol indicated that uptake is independent of requirements for protein synthesis and energy. The organism did not accumulate ethambutol against a concentration gradient. It can be concluded that ethambutol enters the cells in a passive manner. Kinetic studies of
14
C loss from tubercle bacilli pretreated with labeled drug suggested the existence of two ethambutol fractions within the cell: a highly variable labile pool and a second fraction that is small and quite firmly bound. Levels of cell-bound drug may be independent of total uptake, but this possibility was not established unequivocally. Definitive evidence showing identity in the concentrations of bound drug regardless of total uptake could explain the apparent discrepancy between concentration-dependent uptake and concentration-independent growth inhibition.
Antiviral Action of Camptothecin
Authors: Horwitz Susan B. , Chang Chung-Ke , Grollman Arthur P.
Published: June 2012

At a concentration of 10 μ
m
, camptothecin inhibited vaccinia deoxyribonucleic acid (DNA) synthesis in HeLa cells. Inhibition of viral DNA synthesis was observed when the drug was added before infection or at 1 or 2 hr after infection. Inhibitory effects of camptothecin on vaccinia DNA synthesis could be reversed, even after exposure to the alkaloid for 2 hr. Viral DNA, isolated from vaccinia-infected, camptothecin-treated cells, displayed an altered sedimentation constant after alkaline sucrose density gradient centrifugation. Incorporation of uridine into vaccinia messenger ribonucleic acid was inhibited by camptothecin, but the activity of ribonucleic acid polymerase, as tested in isolated vaccinia cores, was not affected by the drug. Camptothecin had essentially no effect on replication of poliovirus in HeLa cells.
In Vitro Antibacterial Activity of Spectinomycin
Authors: Washington John A. , Yu Pauline K. W.
Published: June 2012

The in vitro inhibitory and bactericidal activities of spectinomycin hydrochloride were tested against a variety of bacteria. The antibiotic was inhibitory at 31.2 μg/ml to most strains of
Escherichia coli, Klebsiella, Enterobacter
, and
Staphylococcus epidermidis
. Concentrations of antibiotic exhibiting bactericidal activity exceeded the inhibitory concentration by at least fourfold. Regression graphs were plotted for results obtained with 30-, 100-, 200-, and 300-μg spectinomycin discs; tentative interpretative standards are proposed.
Catabolite Repression in Inhibition of β-Galactosidase Synthesis by
Escherichia coli
in the Presence of Agents Producing Translation Errors
Authors: Artman M. , Werthamer S. , Gelb Phyllis
Published: June 2012

Studies were made of the synthesis of β-galactosidase by
Escherichia coli
in the presence of 5-fluorouracil, streptomycin, and subinhibitory concentrations of chloramphenicol. The preferential inhibition of β-galactosidase synthesis observed in the presence of the above drugs was found to be caused by catabolite repression.
Production of High-Titered Interferon in Cultures of Human Diploid Cells
Authors: Havell Edward A. , Vilček Jan
Published: June 2012

The effect of incubation with interferon prior to the stimulation of interferon production (priming) and of sequential treatment with cycloheximide and actinomycin D (superinduction) on the interferon yield from polyinosinic-polycytidylic acid (poly I·poly C)-induced diploid human foreskin cell cultures (FS-3 strain) was studied. Suitable priming with interferon produced, on the average, about an eightfold increase over the control yield, with a greater increase noted on some occasions when the control interferon yield was very low. Under the optimal conditions carefully defined in our experiments, superinduction produced about a 100-fold increase over the average control yield, resulting in interferon yields of about 10,000 reference units from cultures containing about 10
6
cells. Combined superinduction and priming did not produce yields markedly higher than obtainable by superinduction alone. Essentially similar results were obtained in cultures of human embryonic kidney cells and in FS-3 cells stimulated with other double-stranded polynucleotide inducers. However, stimulation of cells with certain concentrations of a mixture of diethylaminoethyl-dextran and poly I·poly C altered the interferon response; the yield was considerably higher than in cells stimulated with poly I·poly C alone, but it could not be markedly increased further by superinduction.
Relationship of Chemical Structure and Antimicrobial Activity of Alkyl Amides and Amines
Authors: Kabara Jon J. , Conley Anthony J. , Truant Joseph P.
Published: June 2012

Contrary to the limited effects of alkyl amides and their corresponding
N
-derivatives, alkyl amines affected both gram-positive and gram-negative organisms. As with other alkyl derivatives the most sensitive gram-negative bacteria were usually more resistant than the most resistant gram-positive bacteria.

Compounds with a chain-length of 11 to 15 are most active. Although some of the general properties relating the activity of fatty acids to their antimicrobial action are similar to those of amine compounds, the amines are unique in that monounsaturation
does not
increase compound activity.

The possible modes of action of these compounds are discussed.
Susceptibility of
Nocardia asteroides
to 45 Antimicrobial Agents In Vitro
Authors: Bach Michael C. , Sabath Leon D. , Finland Maxwell
Published: June 2012

A method for preparing uniformly dispersed cultures of
Nocardia asteroides
for use in tests for susceptibility to antimicrobial agents is described. The minimal inhibiting concentration (MIC) of 45 agents for cultures thus prepared was determined with the use of a replica-inoculating apparatus. Minocycline at a concentration of 3.1 μg or less/ml inhibited 90% of the strains tested, and all were inhibited by 6.3 μg/ml. An erythromycin concentration of 0.8 μg or less/ml inhibited 40% of the strains, but the MIC for most of the others was > 100 μg/ml. The other agents were generally less active. Chemically related analogues varied in activity to different degrees. Also, the MIC of each antibiotic against different strains generally varied over a wide range. Sulfonamides and trimethoprim were not active against most strains in the method used. The size of the inoculum markedly affected the MIC of sulfonamides and had variable effects on other agents. Marked synergy of erythromycin with ampicillin was demonstrated for nearly all strains tested.
Screening of Isoniazid Inactivators
Authors: Eidus Leslie , Hodgkin Mary M.
Published: June 2012

A method is described for phenotyping of isoniazid inactivators. After a test dose of isoniazid, free isoniazid and its acetyl derivative are estimated in urine by the same colorimetric reaction.
Effect of Hepatic Insufficiency on 5-Fluorocytosine Concentrations in Serum
Authors: Block Edward R.
Published: June 2012

Hepatic function failed to influence serum concentrations of the antifungal agent 5-fluorocytosine when the drug was given intravenously to rabbits with CCl
4
-induced hepatic insufficiency or orally to a patient with postnecrotic cirrhosis.
In Vitro Bactericidal Effectiveness of Four Aminoglycoside Antibiotics
Authors: Hyams Phineas J. , Simberkoff Michael S. , Rahal James J.
Published: June 2012

The antibacterial activity of four aminoglycoside antibiotics (gentamicin, Sch 13706, tobramycin, and sisomicin) was tested against eight gram-negative and three gram-positive species. A total of 323 strains were studied by the broth dilution technique. Tobramycin and sisomicin had greater bacteriostatic and bactericidal activity against
Pseudomonas
strains than did gentamicin and Sch 13706. Of the four antibiotics, sisomicin was most active against
Klebsiella, Enterobacter, Escherichia coli
, indole-negative and -positive
Proteus
, and
Streptococcus pyogenes
. Gentamicin was most effective against
Serratia
. A fourfold or greater difference existed frequently between the minimal inhibitory and bactericidal concentrations of all antibiotics against
Enterobacter
and
Serratia
. This difference was greatest with tobramycin.
Staphylococcus aureus
was highly susceptible,
Providencia
relatively resistant, and enterococcus uniformly resistant to the antibiotics studied. Agar diffusion susceptibility testing with gentamicin and tobramycin showed that organisms susceptible to less than 6.2 μg/ml usually yielded zones 17 to 26 mm in diameters. Zones of 15 to 16 mm represented intermediate susceptibility which varied with the organism and antibiotic. Several
Serratia
strains required 6.2 to 12.5 μg of gentamicin/ml or 25 to 50 μg of tobramycin/ml for bactericidal activity despite minimal inhibitory concentrations of 0.09 to 3.1 μg/ml and zone sizes greater than 13 and 17 mm, respectively. Studies with
Enterobacter
and tobramycin yielded similar results.
Spectrophotometric Method for the Estimation of 6-Aminopenicillanic Acid
Authors: Shaikh Khadija , Talati P. G. , Gang D. M.
Published: June 2012

A simple, rapid, and sensitive method is described whereby 6-aminopenicillanic acid can be spectrophotometrically determined in the presence of penicillins and their degradation products without prior separation.
d
-(+)-Glucosamine is used as reagent. The effect of such parameters as
p
H, temperature, and time of heating on the formation of the chromophore is described. The recommended range is from 25 to 250 μg of 6-aminopenicillanic acid.
A Quinoline Methanol (WR 30090) for Treatment of Acute Malaria
Authors: Martin D. C. , Arnold J. D. , Clyde D. F. , Ibrahim M. Al , Carson P. E. , Rieckmann K. H. , Willerson D.
Published: June 2012

WR 30090 at a dose of 230 mg every 8 hr for 6 days has proven to be a safe, well-tolerated compound with photosensitivity proving to be a minor consideration. WR 30090 was found to be an effective medication for the treatment of acute malaria caused by several strains of
Plasmodium falciparum
. At the dose of 230 mg every 8 hr for 6 days, all of six men infected with a chloroquine-susceptible strain (Uganda I) were cured, all of 13 subjects infected with moderately chloroquine-resistant strains (Malayan Camp, Malayan Taylor, and Philippine Per) were cured, and 19 of 23 subjects infected with strains highly resistant to chloroquine (Vietnam Smith and Vietnam Crocker) were cured. All of five subjects infected with the chloroquine-resistant Vietnam Marks strain were cured with only 3 days of therapy. Blood-induced
P. vivax
(Chesson strain) infection showed a mixed response. Six out of seven volunteers were cured when treated for 3 days with WR 30090. The one recrudescence responded to a repeated course of therapy for 3 days. However, recrudescence occurred in one volunteer treated for 6 days. Treatment with WR 30090 failed to cure sporozoite-induced
P. vivax
(Chesson strain) infection in any of four subjects. In all subjects treated, there was good suppression of parasitemia and relief of symptoms. The susceptibility of the strains of malaria to WR 30090 to some degree parallels their susceptibility to chloroquine.
Mechanism of Chloramphenicol Resistance in Staphylococci: Characterization and Hybridization of Variants of Chloramphenicol Acetyltransferase
Authors: Sands L. C. , Shaw W. V.
Published: June 2012

Fifty clinical isolates of chloramphenicol-resistant staphylococci from diverse sources were screened for the presence of chloramphenicol acetyltransferase (CAT) and were found to contain the inducible chloramphenicol-inactivating enzyme in each case. Polyacrylamide disc gel electrophoresis revealed four distinct types of CAT of which three were purified to a state of homogeneity. Each purified CAT preparation was shown to exist as a tetrameric protein with a native molecular weight of 80,000 and an identical subunit size of 20,000. All four staphylococcal types of CAT exhibited identical catalytic and immunological properties, but they possessed variable sensitivity to heat denaturation and to inhibition by mercuric ion. Each of the three purified variants of staphylococcal CAT was capable of undergoing reversible denaturation in 6
m
guanidine hydrochloride. In vitro hybridization was successful between pairs of each of the three purified staphylococcal enzymes. Only one heteromeric (hybrid) species was observed in addition to the parental types rather than the three predicted from the known quaternary structure of staphylococcal CAT.
Microbial Production of Tenuazonic Acid Analogues
Authors: Gatenbeck Sten , Sierankiewicz Julian
Published: June 2012

The fungus
Alternaria tenuis
normally produces tenuazonic acid (3-acetyl-5-secbutyltetramic acid). On supplementation of the culture substrate with
l
-valine and
l
-leucine, the organism formed two new tetramic acids, 3-acetyl-5-isopropyltetramic acid and 3-acetyl-5-isobutyltetramic acid, respectively.
l
-Phenylalanine was not utilized by the organism as a tetramic acid precursor.
Growth of
Dictyostelium discoideum
in the Presence of Antibiotics
Authors: Love Leslie L. , Chassy Bruce M. , Krichevsky Micah I.
Published: June 2012

Cultures of the amoeboid slime mold,
Dictyostelium discoideum
, were grown in the presence of various antibiotics and antimetabolites. Results indicate that many antibiotics may be used in amoeba cultures to help minimize contamination (for example: polymyxin B, kanamycin, tetracycline, neomycin, oxacillin, ampicillin, cephalothin, and erythromycin). A few potent antibiotics were found to be unsuitable (colistin, nystatin, amphotericin B, actinomycin, and cycloheximide); the mechanisms of the inhibitions observed were not investigated further.
Interaction Between Deoxyribonucleic Acid and Distamycin A Studied by Transformation in
Bacillus subtilis
Authors: Mazza G. , Galizzi A. , Minghetti A. , Siccardi A.
Published: June 2012

Distamycin A inhibits deoxyribonucleic acid (DNA)-mediated transformation and transfection in
Bacillus subtilis
at doses with little or no antibacterial effect. The inhibition of transformation parallels the inhibition of DNA uptake; further-more, during the transformation process, donor DNA molecules become distamycin and deoxyribonuclease resistant at the same time. This demonstrates that the drug acts by inhibiting DNA uptake. Although the drug is known to bind DNA, the inhibition is not related to affinity of the drug for DNA. This is shown by the lack of dependence of the extent of inhibition on DNA concentration, whereas the degree of inhibition depends upon cell concentration. Supporting this view is the fact that transformation by single-stranded DNA was also inhibited, even though the drug does not bind to denatured DNA. Distamycin A probably interferes with transformation by competing with DNA for some unknown bacterial component involved in transport of DNA into the cell.
Treatment of Chronic Typhoid Carriers with Ampicillin
Authors: Johnson Warren D. , Hook Edward W. , Lindsey Edna , Kaye Donald
Published: June 2012

Ten chronic enteric typhoid carriers treated with oral ampicillin have been followed for 4 to 9 years and no relapses have occurred. Patients are probably cured if relapse does not occur within 2 years.
Effect of Isoprinosine Against Challenge with A(H
3
N
2
)/Hong Kong Influenza Virus in Volunteers
Authors: Longley Selden , Dunning R. Lynn , Waldman Robert H.
Published: June 2012

Volunteers were challenged with A(H
3
N
2
)/Hong Kong/8/68 influenza virus while being given prophylaxis with either isoprinosine or placebo in a double-blind experiment. Isoprinosine, which had demonstrable antiviral activity in animal models, did not appear to protect humans from clinical influenza. The only beneficial effect of the drug observed was a slight, but significant, reduction in virus shedding.
Plasmid for Tetracycline Resistance in
Staphylococcus epidermidis
Authors: Minshew Barbara H. , Rosenblum E. D.
Published: June 2012

A plasmid determining tetracycline resistance was demonstrated for
Staphylococcus epidermidis
. Tetracycline resistance was spontaneously lost from a
S. epidermidis
strain at a frequency of <0.1 to 1.3%. Frequency of loss was not appreciably enhanced by growth at 42 C or in ethyl violet. The rate of transduction of tetracycline resistance in three
S. epidermidis
crosses was decreased as a function of ultraviolet irradiation of the transducing phage. Plasmid deoxyribonucleic acid (DNA) associated with tetracycline resistance was isolated by CsCl-ethidium bromide dye-buoyant density gradients. The tetracycline plasmids from
S. aureus
RN 1304 (molecular weight 2.66 Mdals) and
S. epidermidis
367(φ367) (T
367
) cosedimented in 5 to 20% neutral and alkaline sucrose gradients and are therefore of similar molecular weights. An extrachromosomal element in the recipient strain, isolated as covalently closed circular DNA, did not retain its integrity in an alkaline sucrose gradient.
Inhibition of Dihydropteroate Synthetase from
Escherichia coli
by Sulfones and Sulfonamides
Authors: McCullough Jerry L. , Maren Thomas H.
Published: June 2012

The inhibitory action of various diphenylsulfones and sulfonamides on dihydropteroate synthetase partially purified from
Escherichia coli
was examined. 4,4′-Diaminodiphenylsulfone (DDS; I
50
= 2 × 10
−5
M) and the monosubstituted derivatives 4-amino-4′-formamidodiphenylsulfone (I
50
= 5.8 × 10
−5
M) and 4-amino-4′-acetamidodiphenylsulfone (I
50
= 5.2 × 10
−5
M) were effective inhibitors of dihydropteroate synthetase activity. Disubstitution of the arylamine groups of DDS (4,4′-diformamidodiphenylsulfone and 4,4′-diacetamidodiphenylsulfone) resulted in complete loss of inhibitory activity. Both DDS (
K
I
= 5.9 × 10
−6
M) and sulfadiazine (
K
I
= 2.5 × 10
−6
M) were found to be competitive inhibitors of dihydropteroate synthetase. These findings are discussed in regard to the Bell and Roblin theory of structure-activity relationships for
p
-aminobenzoic acid antagonists.
Cephalexin Concentrations in Sputum During Acute Respiratory Infections
Authors: Halprin Gerald M. , McMahon Samuel M.
Published: June 2012

In 20 patients with acute pulmonary infections, sputum purulence, sputum volume, and concentration and excretion of cephalexin in the sputum significantly decreased concurrently during therapy. The concentration of cephalexin in the serum remained unchanged. Significant correlations were observed between drug concentrations in sputum and serum and between drug excretion in sputum and concentration in serum. These observations may be explained by decreased integrity of the “blood-bronchus barrier” during inflammation, with diffusion of serum into bronchial mucus, without the necessity of postulating active transport.
Tetracyclines and Host-Defense Mechanisms
Authors: Forsgren Arne , Gnarpe Håkan
Published: June 2012

The effects of different tetracyclines on the bactericidal action of serum and on phagocytosis and intracellular killing of bacteria were investigated. Opsonization, phagocytosis, and intracellular killing were not significantly affected by any of the investigated tetracyclines. The bactericidal action of serum on
Escherichia coli
was substantially reduced by all tetracyclines investigated. In this respect, doxycycline had a much more pronounced action than the other tetracyclines. The serum bactericidal effect could be completely restored by addition of Mg
2+
.
Lomofungin, an Inhibitor of Ribonucleic Acid Synthesis in Yeast Protoplasts: Its Effect on Enzyme Formation
Authors: Kuo S.-C. , Cano F. R. , Lampen J. O.
Published: June 2012

Lomofungin, an antibiotic active against fungi, yeasts, and bacteria, rapidly inhibits synthesis of ribonucleic acid (RNA) but not protein by protoplasts of
Saccharomyces
strain 1016. With 40 μg of lomofungin/ml, RNA synthesis was almost completely halted after 10 min of incubation; protein synthesis continued for at least 40 min. Since lomofungin inhibits isolated RNA polymerases from yeast, but not in vitro protein synthesis, it is concluded that the primary action of lomofungin in yeast protoplasts is on RNA synthesis. Examination of the pulse-labeled RNA indicated that biosynthesis of both ribosomal precursor RNAs and messenger RNAs was severely inhibited after the protoplasts were incubated with lomofungin for 5 min, whereas formation of small-molecular-weight RNA (4 to 5
s
) was only slightly affected. Under these conditions, lomofungin almost completely prevented induction of α-glucosidase. Once the protoplasts had been induced, further production of the enzyme was not impaired by lomofungin until after 30 min of incubation, but was rapidly halted by cycloheximide (4 μg/ml). Lomofungin inhibition of invertase formation by protoplasts actively synthesizing the enzyme also became evident only after a lag of about 30 to 40 min, although synthesis was promptly halted by cycloheximide. These observations suggest the existence of relatively long-lived specific messenger RNAs for these enzymes.
Effect of Puromycin Analogues and Other Agents on Peptidyl-Puromycin Synthesis on Polyribosomes
Authors: Pestka Sidney , Vince Robert , Daluge Susan , Harris Raymond
Published: June 2012

The incorporation of [
3
H]puromycin into nascent polypeptide chains of polyribosomes has proved to be a sensitive method of evaluating effects of inhibitors on peptide bond synthesis. Several analogues of puromycin were found to react with polyribosomes from both bacteria and rat liver. The

K
m

for puromycin is 4 μM with bacterial polyribosomes; under the same conditions, the

K
i

for ψ-hydroxy-puromycin (6-dimethylamino-9-[3-(
l
-β-phenyllactylamino)-3-deoxy-β-
d
-ribofuranosyl] purine) is 240 μM and for a carbocyclic analogue of puromycin (6-dimethylamino-9- {R- [2R-hydroxy-3R- (p-methoxyphenyl-
l
-alanylamino)]-cyclopentyl}purine) is 1 μM. Both were found to be competitive inhibitors of puromycin. The

K
m

for C-A-C-C-A(Phe) is 250 μM. In addition, the dissociation constant for C-A-C-C-A(Phe) binding to washed ribosomes was found to be 1 and 0.03 μM in the absence and presence, respectively, of 20% (vol/vol) ethanol. The results with these analogues lead to the following conclusions. Substitution of a hydroxyl group for the α-amino group of puromycin results in an active analogue with about one-sixtieth the affinity of puromycin in the reaction. Omission of the 5′-hydroxymethyl group or substitution of the furanosyl ring oxygen by a carbon atom in the carbocyclic analogue reduces its activity compared with puromycin only slightly. Additionally, the relatively high

K
m

for C-A-C-C-A(Phe) as an acceptor compared with puromycin suggests the existence of a protective mechanism on polyribosomes, which prevents aminoacyl-transfer ribonucleic acid (tRNA) free in solution from stripping nascent chains from polyribosomes so that only aminoacyl-tRNA bound to ribosomes through the appropriate coding mechanism can form a peptide bond.
Characterization and Extrachromosomal Control of Bacteriocin Production in
Staphylococcus aureus
Authors: Jetten A. M. , Vogels G. D.
Published: June 2012

About 6% of the tested strains of
Staphylococcus aureus
produced antagonistic substances against staphylococcal indicator strains. The production was low in liquid cultures and could not be induced by ultraviolet irradiation or by treatment with mitomycin C. The antagonistic substances could be classified into at least five groups on the basis of their properties and cross-resistance pattern. One group consisted of lytic enzymes and the four others of staphylococcins. One of the four types of staphylococcins was active against
S. aureus
only, and the three other types had a broader inhibitory spectrum against gram-positive organisms but not against gram-negative bacteria. A relationship was found between some groups of producing strains and their phage type. The ability to produce staphylococcins was eliminated spontaneously upon storage and more rapidly by treatment with ethidium bromide, acriflavine, acridine orange, sodium dodecyl sulfate, and growth at 42 C. The resistance to several inorganic salts was co-eliminated. No co-elimination of penicillinase production was observed. Selective effects during elimination were ruled out, and the results suggest that the genes for staphylococcin production are plasmid-borne determinants.
Screening and Isolation of Penicillinase Inhibitor, KA-107
Authors: Iwai Y. , Ohno H. , Takeshima H. , Yamaguchi N. , Ōmura S. , Hata T.
Published: June 2012

It is known that penicillin resistance of bacteria is mainly caused by the inactivation of penicillin by penicillinase derived from such strains. We have developed a screening procedure for penicillinase inhibitors. Several microorganisms were found to produce such inhibitors, and from the culture filtrate of
Streptomyces gedanensis
ATCC 4880 a penicillinase inhibitor, named KA-107, was isolated. The characteristics of this inhibitor were revealed by an in vitro test by using penicillinase derived from penicillin resistant
Staphylococcus aureus
, FS-1277. When KA-107 was used in combination with penicillin-G, ampicillin,
d
- or
l
-phenethicillin, the growth inhibitory activity of these penicillins was maintained.
Inactivation of
Herpesvirus hominis
Types 1 and 2 by Silver Nitrate In Vitro and In Vivo
Authors: Coleman V. R. , Wilkie J. , Levinson W. E. , Stevens T. , Jawetz E.
Published: June 2012

Herpes simplex virus (HSV) types 1 and 2 (two strains each) were inactivated at different rates in vitro by 40 μM AgNO
3
. The inactivation of HSV type 1 strains was virtually complete in 10 to 15 min, whereas almost half of the infectivity of HSV type 2 strains survived this exposure. One strain of type 1 inoculated into rabbit eyes was almost completely inactivated by 1% AgNO
3
solution dropped into the eye 20 min later, so that there was markedly reduced viral replication and less corneal herpetic disease. One strain of HSV type 2 in the rabbit eye was not effectively inactivated by 1% AgNO
3
. From these results, it seems likely that AgNO
3
instillation into the eyes of a newborn who has passed through a birth canal infected with HSV might prevent eye infection with HSV type 1 but not with type 2. The greater resistance of HSV type 2 strains to chemical inactivation in vitro and in vivo may be of medical concern.
Antiviral Effects of Aphidicolin, a New Antibiotic Produced by
Cephalosporium aphidicola
Authors: Bucknall R. A. , Moores H. , Simms R. , Hesp B.
Published: June 2012

Aphidicolin is an antibiotic of novel structure produced by the mold
Cephalosporium aphidicola
. It is a potent inhibitor of cellular deoxyribonucleic acid synthesis, and it also strongly inhibits the growth of herpes simplex virus both in tissue culture and in the rabbit eye. Aphidicolin is active against iododeoxyuridine-resistant herpes virus, and does not itself readily induce the formation of drug-resistant strains of herpesvirus.
Phleomycin-Stimulated Degradation of Deoxyribonucleic Acid in
Escherichia coli
Authors: Farrell Larry , Reiter Harvard
Published: June 2012

Phleomycin stimulates the degradation of DNA by energy-dependent endonuclease and exonuclease reactions in
Escherichia coli rec
+
cells and in
recB
−
and
recC
−
cells that lack an adenosine triphosphate-dependent nuclease functioning in the repair of ultraviolet (UV) lesions. Exonuclease activity is blocked in T4 phage-infected cells. The endonuclease reaction produces 10
7
-dalton segments resembling those produced in colicin E2-treated cells. These differ from the random-sized segments produced in UV-irradiated cells, or the 10
6
-dalton segments made in T4 phage-infected cells. A mutant selected for phleomycin tolerance is cross-tolerant to colicin E2, and some mutants selected for colicin E2 tolerance are cross-tolerant to phleomycin. On the basis of these cross-tolerances and the similarities between the effects of phleomycin and E2-stimulated nucleases, the suggestion is made that both agents may stimulate the same nuclease reactions in
E. coli
cells.
Inducible and Constitutive Resistance to Macrolide Antibiotics and Lincomycin in Clinically Isolated Strains of
Streptococcus pyogenes
Authors: Hyder Sylvia Lubna , Streitfeld Murray M.
Published: June 2012

Studies on erythromycin resistance in strains of group A streptococci indicated that they were comprised of two types: (i) an inducible, resistant type (IR strains) was seen, which manifested immediate logarithmic growth in media containing high concentrations of the drug only after brief previous exposure (induction period) of the organisms to subinhibitory concentrations of erythromycin, and (ii) a constitutive, resistant type (CR strains) which demonstrated, without prior drug exposure, continued logarithmic growth in media containing high concentrations of erythromycin. Subinhibitory concentrations of either chloramphenicol or puromycin, when added to IR strains prior to induction, interfered with their induction by erythromycin. Exposure of CR strains to chloramphenicol did not visibly affect the subsequent growth curve of these strains in media containing high concentrations of erythromycin. In IR strains, resistance to other macrolide antibiotics (oleandomycin, spiramycin, carbomycin, magnamycin) and to lincomycin also was inducible in nature. There was cross-inducibility between erythromycin, other macrolide antibiotics, and lincomycin. CR strains were constitutively resistant to these antibiotics.
New Synthetic Antibacterial Compound, 1-(2-Hydroxyethyl)-3-Nitro-4-Pyrazolecarboxamide
Authors: Wick W. E. , Preston D. A. , Terando N. H. , Welles J. S. , Gordee R. S.
Published: June 2012

A series of 3-nitropyrazole compounds represent a new class of synthetic antibacterial agents. One member of this series, 1-(2-hydroxyethyl)-3-nitro-4-pyrazolecarboxamide, exhibited an antibacterial spectrum similar to that of nitrofurantoin. The inhibitory concentrations of this nitropyrazole were lower than those required for nitrofurantoin. Single oral doses of 20 mg/kg resulted in peak nitropyrazole concentrations of 5.8 and >1,000 μg/ml in mouse blood and urine, respectively. In dogs, 87% of a 10 mg/kg oral dose was recovered in urine during a 24-h period with a peak serum concentration of 13.6 μg/ml. This nitropyrazole was highly effective against experimental bacterial infections in mice. The low acute toxicity in mice, rats, or dogs and significant antibacterial activity lead to the conclusion that further evaluation of this compound is warranted.
Lipid Composition of Gram-Negative Bacteria, Sensitive and Resistant to Streptomycin
Authors: Bishop Elizabeth A. , Bermingham Margaret A. C.
Published: June 2012

Analyses of streptomycin-sensitive and -resistant gram-negative bacteria show that, contrary to previous reports, the development of antibiotic resistance is not accompanied by changes in membrane lipid or fatty acid composition.
Antifungal Properties of 2-Alkenoic Acids and 2-Bromo Alkanoic Acids
Authors: Gershon Herman , McNeil Maynard W. , Parmegiani Raulo , Godfrey Patricia K. , Baricko Janice M.
Published: June 2012

The antifungal activity of homologous series of 2-alkenoic and 2-bromo alkanoic acids was determined against
Aspergillus niger, Trichoderma viride, Myrothecium verrucaria
, and
Trichophyton mentagrophytes
and compared with data on analogous alkanoic and 2-fluoro alkanoic acids. The fungitoxicity of all of the series of compounds was determined by chain length, pH of the medium, and presence or absence of adsorbents such as serum albumin. The order of toxicity on a molecular basis, by using a scale where the most active series is 1.0, is 2-bromo alkanoic acids (1.0) > 2-fluoro alkanoic acids (1.2) > alkanoic acids (1.4) > 2-alkenoic acids (2.5).
Transferable Antibiotic Resistance in Enteropathogenic
Escherichia coli
Between 1948 and 1968
Authors: Slocombe B. , Sutherland R.
Published: June 2012

Enteropathogenic strains of
Escherichia coli
which had been isolated in the United Kingdom during three periods between 1948 and 1968, namely 1948 to 1951, 1957 to 1960, and 1967 to 1968, were tested for susceptibility to ampicillin, streptomycin, tetracycline, chloramphenicol, and sulphonamides. Antibiotic-resistant strains were tested for their ability to transfer antibiotic resistance to an antibiotic-susceptible strain of
E. coli
K-12. A relatively high proportion of strains isolated between 1948 and 1951 was resistant to ampicillin, streptomycin, or sulphonamides. None of these strains transferred ampicillin or streptomycin resistance, but sulphonamide resistance was R-factor-mediated in three out of 14 sulphonamide-resistant strains. Resistance to tetracycline and chloramphenicol was rare before 1951 but had become common among enteropathogenic
E. coli
by 1957. Much of the antibiotic resistance of bacteria isolated between 1957 and 1960 was R-factor-mediated, and transferable resistance was about as prevalent among
E. coli
isolated between 1957 and 1960 as among strains isolated in 1967 and 1968. Nevertheless, there was no appreciable increase in the overall incidence of antibiotic resistance among these enteropathogenic strains of
E. coli
between 1957 and 1968, although transferable antibiotic resistance was common during this period. These results do not suggest that the emergence of transferable antibiotic resistance will inevitably lead to the rapid development of antibiotic resistance among this group of bacteria.
Lysine Biosynthesis in
Streptomyces lipmanii
: Implications in Antibiotic Biosynthesis
Authors: Kirkpatrick J. R. , Doolin L. E. , Godfrey O. W.
Published: June 2012

Streptomyces lipmanii
produces two β-lactam antibiotics, penicillin N and 7-(5-amino-5-carboxyvaleramido)-7-methoxycephalosporanic acid. Both antibiotics contain α-aminoadipic acid side chains. In similar antibiotics produced by certain fungi, the α-aminoadipoyl moiety is derived from an intermediate in lysine biosynthesis. Our findings indicate, however, that in
S. lipmanii
, lysine is synthesized via α, ε-diaminopimelic acid—an entirely different biosynthetic route. This finding suggests not only a unique mechanism for the derivation of α-aminoadipate, but also that the system may be particularly amenable to genetic manipulation.
Isolation and Identification of Minor Components of Commercial Kanamycin
Authors: Claes Paul J. , Vanderhaeghe Hubert , Compernolle Frans
Published: June 2012

A fraction enriched in the minor components of the kanamycin complex was prepared from a commercial sample. The enriched fraction was subjected to Amberlite CG-50 and Dowex 1-X2 column chromatography. Two minor components were isolated in addition to the known A, B, and C components. These congeners were identified as paromamine and 6-
o
-(3-amino-3-deoxy-α-
d
-glucopyranosyl)- deoxystreptamine. The identification was based on degradation and mass spectral studies.
Characterization of a Bacteriocin from
Staphylococcus aureus
Strain 462
Authors: Hale E. M. , Hinsdill R. D.
Published: June 2012

Staphylococcus aureus
462 is one of three bacteriocin-producing strains selected for study from 200 isolates of staphylococci of animal origin. These bacteriocins are specific in their activity, inhibiting the growth of certain strains of
S. aureus
and other gram-positive species, but not gram-negative organisms. Staphylococcin 462 was not found in significant concentrations in the supernatant fluid of broth cultures, nor was it released into the suspending liquid when the cells were mechanically disrupted. However, extraction of the cells with 7 M urea resulted in the liberation of much of the activity. The material was purified by gel permeation chromatography by using Sephadex G-200 and by preparative electrophoresis on polyacrylamide gels in the presence of sodium dodecyl sulfate. Chemical analysis showed that the material consisted of roughly 90% protein and 3% lipid. The molecular weight of sodium dodecyl sulfate-dissociated staphylococcin 462 was calculated to be about 9,000.
Antiviral Activity of
N
-Phenyl-
N
′-Aryl- or Alkylthiourea Derivatives in Coxsackie Virus Infections in Mice
Authors: Galabov Angel S. , Velichkova Emilia H.
Published: June 2012

The effect of five derivatives of
N
-phenyl-
N
′-aryl- or alkylthiourea—inhibitors of the multiplication of Coxsackie virus B1 and other picornaviruses in vitro—was tested in experimental infections with Coxsackie viruses B1, B3, A6, and A7 in newborn mice. Under the action of
N
-phenyl-
N
′-3-hydroxyphenylthiourea (no. 23) and
N
-phenyl-
N
′-4-carboxy-5-hydroxyphenylthiourea (no. 20) a two- to threefold reduction in mortality was observed, as well as an appreciable delay in the course of the disease (mean effective dose, lengthening by 2 to 6 days) after infection with Coxsackie viruses B1, B3, and A7. The infection with Coxsackie virus A6 was affected only by compound no. 23 and, at that, to a low degree. If the antiviral effect is to be obtained, the compounds must be applied daily (once subcutaneously) from the 24th to the 144th h after virus inoculation, a period which corresponds to the incubation period and the beginning of the manifested infection. On the basis of these data, as well as of the relatively high selectivity (therapeutic index of 3 to 20), the two indicated substances may be considered to be reliable antiviral chemotherapeutic agents.
Cefoxitin, a Semisynthetic Cephamycin Antibiotic: Susceptibility Studies
Authors: Wallick Hyman , Hendlin David
Published: June 2012

Cefoxitin, 3-carbamoyloxymethyl-7-α-methoxy-7-[2-(2-thienyl)acetamido]-3-cephem-4- carboxylic acid, is a new semisynthetic cephamycin with broad antibacterial activity. It is highly active against gram-negative microorganisms including indole-positive
Proteus
and
Serratia
strains, which are ordinarily reistant to the cephalosporins. Cefoxitin is also highly active against many strains of
Escherichia coli
and
Proteus mirabilis
which are resistant to the cephalosporins. Furthermore,
E. coli
and
Klebsiella
strains which are susceptible to the cephalosporins are generally more susceptible to the cephamycin analog. The susceptibility of the gram-positive bacteria falls well within the effective range of the antibiotic for gram-negative organisms, but cefoxitin is less active than cephalothin or cephaloridine. As is the case with the cephalosporins, strains of
Pseudomonas
and group D streptococci are resistant to cefoxitin. Changes in pH, inoculum density, and growth medium have no significant effect on the activity of the antibiotic.
Clinical Study of the Use of the New Aminoglycoside Tobramycin for Therapy of Infections Due to Gram-Negative Bacteria
Authors: Jaffe Gabriel , Ravreby William , Meyers Burt R. , Hirschman Shalom Z.
Published: June 2012

Tobramycin, a new aminoglycoside antimicrobial, was evaluated as therapy for infections due to gram-negative bacilli in 15 seriously ill patients with underlying diseases. Three of 10 patients with gram-negative bacteremias also had urinary tract infections. Two patients had respiratory tract infections, one had cellulitis, one had a urinary tract infection, and another had septic phlebitis. Twelve patients were cured of their infections. Eosinophilia was observed in one patient and another developed superinfection with
Staphylococcus aureus
after 6 days of tobramycin therapy. There were five isolates of
Escherichia coli
, five of
Klebsiella
sp., two of
Pseudomonas
sp., and one each of
Enterobacter agglomerans, Serratia marcescens
, and
Enterobacter cloacae
. The average serum concentration of tobramycin 2 h after a parenteral dose of 1.0 to 1.5 mg/kg was 5.1 μg/ml; higher concentrations of tobramycin were present in urine. Tobramycin proved to be an effective antimicrobial in these patients.
Selective Phosphorylation of the 5′′-Hydroxy Group of Ribostamycin by a New Enzyme from
Pseudomonas aeruginosa
Authors: Kida Makoto , Igarasi Seizi , Okutani Tetsuya , Asako Tsunehiko , Hiraga Kentaro , Mitsuhashi Susumu
Published: June 2012

It was found that the 5′′-hydroxy group of ribostamycin was preferentially phosphorylated by a cell-free extract from
Pseudomonas aeruginosa
GN 573, a clinical isolate.
Interaction Between Acetohydroxamic Acid and 12 Antibiotics Against 14 Gram-Negative Pathogenic Bacteria
Authors: Musher Daniel M. , Saenz Corando , Griffith Donald P.
Published: June 2012

Acetohydroxamic acid (AHA) is a potent inhibitor of urease which prevents alkalinization of urine and stone formation in rats in the presence of infection caused by urease-producing bacteria. Because an antibacterial effect of AHA, and synergy between kanamycin and AHA have also been described, we studied the interaction between AHA and 12 antibiotics against 14 gram-negative bacteria. Synergy, sometimes to a striking degree, was found in 17% of interactions; however, antagonism was detected in 5%. Infecting organisms would need to be studied individually before the antibacterial effect of AHA and an antibiotic could be predicted.