bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence for Participation of Autolysins in Bactericidal Action of Oxacillin on
Staphylococcus aureus
Authors: Best Gary K. , Best Norma H. , Koval Ann V.
Published: June 2012

A comparison of the autolytic enzyme activity in
Staphylococcus aureus
strains that differ markedly in their rates of lysis and killing after exposure to oxacillin has been made. Log-phase cells of the clinical isolate that is tolerant to oxacillin inhibition were found to contain a level of autolytic enzyme activity comparable to that in a sensitive strain. This autolysin from log-phase cells was recovered after a single freeze-thaw cycle and assayed by using both native and penicillin (un-cross-linked) mureins. These same assays, however, revealed a significant difference in autolysin activity extractable from the two strains if the cells were inhibited by oxacillin. Under these conditions, the
S. aureus
strain that is susceptible to the killing and lytic effects of oxacillin had considerably more activity on penicillin murein than did the tolerant organism. These results provide evidence that hydrolytic enzymes on the cell surface are required to augment the wall damage initiated by oxacillin and other β-lactam antibotics to produce a bactericidal effect.
Pharmacokinetics of Gentamicin and Kanamycin During Hemodialysis
Authors: Danish Michele , Schultz Robert , Jusko William J.
Published: June 2012

The pharmacokinetics of gentamicin, kanamycin, and creatinine were studied in patients undergoing hemodialysis. After intravenous injection of single doses of the drugs, 50 to 60% of the doses of both antibiotics were cleared from the body during a 6-h period; this occurred almost entirely by the hemodialysis process. No correlation was found between the dialysance of the aminoglycosides and creatinine. The pharmacokinetic data were used to make dosage regimen recommendations for treatment of hemodialysis patients with these antibiotics.
Studies on the Regulation of Colicin Ib Synthesis: Replication of the Col Ib-P9 Plasmid During Colicin Induction
Authors: Isaacson R. E. , Konisky J.
Published: June 2012

The Col Ib-P9 plasmid content of colicinogenic cells has been measured by both sedimentation analysis of cleared lysates and by deoxyribonucleic acid hybridization to purified Col Ib-P9 factor deoxyribonucleic acid. The results show an independence between mitomycin C-induced colicin synthesis and Col Ib-P9 replication. In addition, the ratio of the various molecular configurations (i.e., covalently closed circles or open circles) of the Col Ib-P9 plasmid does not change upon induction of colicin synthesis. Heat treatment of a colicinogenic strain carrying a thermosensitive
dna
B mutation on the bacterial chromosome leads to complete inhibition of Col Ib-P9 plasmid replication and the simultaneous induction of colicin Ib synthesis in all cells of the colicinogenic population. These studies rule out mechanisms or regulation of colicin Ib synthesis based on the induced replication of the Col Ib-P9 plasmid. Our studies show that in a Col Ib-P9 colicinogenic population there is, on the average, one plasmid per cell.
Effect of Enrichment Procedure upon Auxotroph Recovery in
Escherichia coli
K-12
Authors: Rossi John J. , Berg Claire M.
Published: June 2012

Proline-requiring auxotrophs are recovered preferentially after mutant enrichment procedures (e.g., penicillin) which perturb the cell envelope, but not after procedures (e.g., thymineless death) which affect other cellular targets. This probably stems from effects of penicillin and similar antibiotics upon proline metabolic and transport enzymes associated with the cell envelope.
Broth-Dilution Method for Determining the Antibiotic Susceptibility of Anaerobic Bacteria
Authors: Stalons Donald R. , Thornsberry Clyde
Published: June 2012

A broth-dilution method for performing antimicrobial susceptibility tests on anaerobic bacteria has been proposed. The medium used in the test was Schaedler broth, with incubation in a glove box with an atmosphere of 5% CO
2
, 10% H
2
, and 85% N
2
, or in the GasPak system. Minimal inhibitory concentrations for selected antibiotics were determined, under these conditions, by using a conventional twofold dilution scheme for the antibiotics and a “categorization three-tube method” in which two or three clinically significant concentrations of each antibiotic were used. Minimal inhibitory concentrations obtained by both methods were very similar. The categorization method could be used routinely to test the antimicrobial susceptibility of anaerobic bacteria.
Effect of Lincomycin and Clindamycin on Peptide Chain Initiation
Authors: Reusser Fritz
Published: June 2012

Lincomycin does not affect initiation factor-dependent formation of 70
S
initiation complexes formed with fmet-tRNA
F
, the initiation triplet A-U-G, and 70
S
ribosomes, whereas its 7-chloro-derivative clindamycin substantially stimulates this process. Conversely, lincomycin stimulates nonenzymatic formation of the 70
S
complex, but clindamycin does not. Both antibiotics stimulate the assembly of non-enzymatically formed 70
S
initiation complexes with R
17
phage ribonucleic acid and exert little effect on those formed in the presence of initiation factors. The formation of 30
S
initiation complexes is stimulated or remains unaffected by lincomycin or clindamycin except when initiation occurs in the presence of very low Mg
2+
concentrations. In this case, both antibiotics inhibit the assembly of the 30
S
complexes regardless of the messenger present.
Mechanism of Plasmid-Mediated Resistance to Cadmium in
Staphylococcus aureus
Authors: Chopra I.
Published: June 2012

The mechanism of plasmid-mediated resistance to cadmium in
Staphylococcus aureus
was investigated. Protein synthesis in cell-free extracts from resistant or susceptible bacteria was equally susceptible to inhibition by Cd
2+
, but spheroplasts from resistant bacteria retained their resistance. Resistant bacteria did not have a decreased affinity for cations in general, nor was active metabolism required for exclusion of Cd
2+
. The kinetics of Cd
2+
uptake into susceptible and resistant bacteria suggested that the conformation of membrane proteins in resistant bacteria may be important in the exclusion of Cd
2+
.
Isolation and Characterization of a γ-Thiochromanone-4-Thiosemicarbazone-Resistant Mutant of Vaccinia Virus
Authors: Katz Ehud , Margalith Eva , Winer Bela
Published: June 2012

γ-Thiochromanone-4-thiosemicarbazone (TCT) inhibits the growth of vaccinia virus in BSCl cells by interfering with viral maturation. A mutant of the virus (TCT
R
) which is resistant to this drug was isolated. This mutant also exhibits resistance to another thiosemicarbazone related compound, isatin β-thiosemicarbazone (IBT). There is a good correlation between the cross-resistance of the two mutants IBT
R
and TCT
R
to TCT and IBT, respectively, and the similar antipoxvirus activity of these two thiosemicarbazone-related compounds.
Mode of Action of Two
Streptococcus faecium
Bacteriocins
Authors: Krämer J. , Brandis H.
Published: June 2012

The mechanism of action of enterocins E1A and E1B, bacteriocins produced by
Streptococcus faecium
E1, was studied. The enterocins killed susceptible cells rapidly, but cell lysis does not appear to be involved directly. Susceptible cells could be rescued from the lethal damage by trypsin treatment only within 2 to 3 min after addition of enterocin E1A. Enterocins E1A and E1B inhibited protein synthesis and drastically reduced biosynthesis of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) but did not cause degradation of DNA or RNA. Enterocin E1A strongly inhibited the accumulation of isoleucine and caused rapid exit of previously accumulated isoleucine.
Disparity Between Inhibitory and Killing Effects of BL-P1654
Authors: Kurtz Stephen , Holmes King , Turck Marvin
Published: June 2012

The activity of BL-P1654, a semisynthetic penicillin, was studied in vitro against
Enterobacteriaceae
and compared with carbenicillin against
Pseudomonas
. There was a marked diminution in bactericidal activity of BL-P1654 when tested in broth medium.
Purification of Two
Clostridium
Bacteriocins by Procedures Appropriate to Hydrophobic Proteins
Authors: Clarke D. J. , Robson R. Moyra , Morris J. G.
Published: June 2012

Two clostridocins distinguishable by their different modes of action on
Clostridium pasteurianum
have been isolated, namely, butyricin 7423 found in cultures of
Clostridium butyricum
NCIB 7423 and perfringocin 11105 produced by
Clostridium perfringens
type A, NCIB 11105. Both were trypsin-susceptible proteins which were soluble in concentrated aqueous ethanol and were able to bind large amounts of the nonionic detergent Triton X-100. In the presence of Triton X-100, butyricin 7423 behaved as a hydrophobic protein in being concentrated in the polyethylene glycol layer of a three-phase partition system of dextran-Ficoll-polyethylene glycol. Their capacity to bind Triton X-100 was exploited in a purification procedure applicable to both bacteriocins. After aqueous ethanol extraction of an ammonium sulfate-precipitated fraction (and, in the case of the perfringocin, a heat-treatment step), a bacteriocin-Triton X-100 adduct was purified by gel filtration through Sepharose 6B. The bacteriocin was then freed of Triton X-100 by chromatography on Sephadex LH-20. Samples of butyricin 7423 purified in this way from different sources contained variable amounts of carbohydrate. Yet sodium dodecyl sulfate-gel electrophoresis revealed the existence of a polypeptide component of 32,500 daltons (±10%), which displayed the biological activity of butyricin 7423 in the absence of any detectable associated carbohydrate (or lipid). Preparations of perfringocin 11105 contained no carbohydrate or lipid and migrated in sodium dodecyl sulfate-gel electrophoresis as a single protein component of 76,000 daltons (±10%). It was concluded that both bacteriocins behave as amphiphilic proteins, and some implications of this finding are considered.
Microdilution Technique for Antimicrobial Susceptibility Testing of Anaerobic Bacteria
Authors: Rotilie Carol A. , Fass Robert J. , Prior Richard B. , Perkins Robert L.
Published: June 2012

A microdilution technique using commercially available media and materials was developed and used to determine the minimal inhibitory concentrations (MICs) of clindamycin, chloramphenicol, tetracycline, minocycline, ampicillin, carbenicillin, cephalothin, and gentamicin for 101 anaerobic isolates. Representative strains of
Bacteroides, Clostridium, Fusobacterium, Peptococcus
, and
Peptostreptococcus
were tested. The use of Schaedler broth at pH 7.2, an inoculum of 10
5
to 10
7
colony-forming units per ml, and incubation at 35 C in an anaerobic glove box with an atmosphere of 80% nitrogen, 10% hydrogen, and 10% carbon dioxide resulted in good growth and easily interpretable results. After 48 h of incubation, 97% of strains tested were inhibited by 3.1 μg or less of clindamycin per ml and 98% were inhibited by 12.5 μg or less of chloramphenicol per ml. Tetracycline and minocycline inhibited 81 and 88% of strains tested in concentrations of 1.6 μg or less per ml and 1.6 μg or less per ml, respectively. Ampicillin inhibited all strains other than
B. fragilis
in concentrations of 3.1 μg or less per ml. Excluding certain strains of
Bacteroides
and
Clostridium
, carbenicillin in concentrations of 12.5 μg or less per ml and cephalothin in concentrations of 6.2 μg or less per ml inhibited all strains tested. Gentamicin was inactive although some strains of anaerobic cocci and
Bacteroides
were inhibited by 3.1 μg or less per ml. After 18 to 24 h of incubation, eight of the 101 strains had not grown sufficiently for MICs to be determined; for the 93 strains which had grown sufficiently, 93% of 744 MICs were the same or one concentration lower than the 48-h MICs.
Stimulation of Derepressed Enzyme Synthesis in Bacteria by Growth on Sublethal Concentrations of Chloramphenicol
Authors: Ford Sharon R. , Switzer R. L.
Published: June 2012

Culturing of
Salmonella typhimurium
or
Escherichia coli
cells in the presence of low concentrations (≤1 μg/ml) of chloramphenicol (CAP) permitted exponential growth, but at doubling times up to twice those of controls. When such cultures were subsequently starved for uracil or arginine, derepression of aspartate transcarbamylase (ATCase) or ornithine transcarbamylase, respectively, was enhanced three- to 10-fold as compared to cultures not exposed to CAP. Enhancement of β-galactosidase synthesis by prior exposure to CAP was also observed in uracil-starved
E. coli
cultures. Stimulation of enzyme synthesis appeared to be a specific effect of CAP; low levels of erythromycin, puromycin, sparsomycin, tetracycline, and rifampin did not show such effects. Derepression of ATCase synthesis in exponentially growing cells in the presence of CAP did not result in stimulation of enzyme synthesis by CAP. A prior history of growth of a culture in the presence of CAP was shown to be necessary for enhancement of enzyme synthesis by CAP; furthermore, continued presence of CAP in the medium during starvation was not necessary for enhanced enzyme synthesis and inhibited it in some instances. Enhanced enzyme synthesis in starving, CAP-treated cultures could be blocked by rifampin, which suggested that CAP treatment allows prolonged or more extensive messenger ribonucleic acid synthesis.
dd
-Carboxypeptidase and Peptidoglycan Transpeptidase from
Pseudomonas aeruginosa
Authors: Presslitz Joseph E. , Ray Verne A.
Published: June 2012

Peptidoglycan transpeptidase and
dd
-carboxypeptidase have been detected in isolated membranes of
Pseudomonas aeruginosa
. Cephalosporins and penicillins fail to inhibit the transpeptidase at concentrations as high as 100 μg/ml.
dd
-Carboxypeptidase, on the other hand, is sensitive to inhibition by β-lactam antibiotics. The presence of dimethyl sulfoxide in the reaction mixture results in a twofold stimulation of peptidoglycan formation, whereas
dd
-carboxypeptidase is inhibited approximately 30%. Maximum stimulation of transpeptidase occurs in the presence of both dimethyl sulfoxide and a β-lactum antibiotic. This is in sharp contrast to the transpeptidase from
Escherichia coli
, which is sensitive to inhibition by penicillins and cephalosporins.
Efficacy of 1-β-
d
-Ribofuranosyl-1,2,4-Triazole-3-carboxamide Against Influenza Virus Infections in Mice
Authors: Durr F. E. , Lindh H. F. , Forbes M.
Published: June 2012

1-β-
d
-Ribofuranosyl-1,2,4-triazole-3-carboxamide (ribavirin) was effective against strains of influenza virus types A and F, whereas amantadine hydrochloride was effective only against strains of influenza virus type A. Dose-related protective effects against lethal influenza infections in mice were obtained with single oral doses of 25 to 400 mg of ribavirin per kg administered at the time of virus inoculation or up to 24 h thereafter. Therapeutic indexes (maximum tolerated dose/median effective dose) against various strains of influenza virus ranged from 5 to 35. With multiple-dose treatment initiated immediately after virus inoculation, oral doses as low as 12 to 25 mg/kg twice daily also afforded significant protection. Treatment with ribavirin inhibited the growth of influenza virus in the lungs of mice and delayed by about 24 h the attainment of maximal viral titers, which in nontreated mice were reached within 24 to 48 h. Inhibition of viral growth was correlated with a suppression of lung consolidation. Ribavirin appears to exert its protective effects against influenza infections by inhibiting virus growth, thereby preventing virus titers from reaching levels that result in massive lung tissue destruction and death of the mice.
Branched-Chain Amino Acid Substitutions in the Biosynthesis of the Antibiotic Actinomycin
Authors: Yajima Takehiko , Mason Kaarin T. , Katz Edward
Published: June 2012

Actinomycins normally contain
N
-methyl-
l
-valine and either
d
-valine,
d
-alloisoleucine or both amino acids in the molecule. During antibiotic formation in a medium supplemented with one of the four isoleucine stereoisomers,
Streptomyces parvulus
and
S. chrysomallus
form complex actinomycin mixtures (C
1
, C
2
, C
3
, E
1
, and E
2
-like compounds). Although chromatographic techniques suggested that single homogeneous components had been isolated, subsequent studies indicated that such chromatographic fractions probably consisted of multiple isomers of actinomycin. Amino acid analyses revealed the presence of
N
-methylvaline and/or
N
-methylalloisoleucine and, in addition,
d
-isoleucine,
d
-valine, and
d
-alloisoleucine were frequently found in a given fraction.
In Vitro Susceptibility of
Pseudomonas cepacia
and
Pseudomonas maltophilia
to Trimethoprim and Trimethoprim-Sulfamethoxazole
Authors: Moody Marcia R. , Young Viola M.
Published: June 2012

Our earlier studies had shown that the two pseudomonads,
Pseudomonas cepacia
and
Pseudomonas maltophilia
, were organisms that were highly resistant to most antibiotics. The present study was undertaken to determine the susceptibility of these bacteria to trimethoprim and the trimethoprim-sulfamethoxazole combination which has been used with apparent success in treating infections caused by these pseudomonads. All 51 strains of
P. cepacia
were inhibited by 2 μg or less of trimethoprim per ml, whereas all 45 of the
P. maltophilia
were resistant to greater than 32 μg/ml. When the
P. maltophilia
was tested against trimethoprim-sulfamethoxazole, two strains were resistant and one only moderately resistant, but all other strains were susceptible. All
P. cepacia
strains were also susceptible with an average zone of inhibition significantly larger than for
P. maltophilia
(
P
< 0.005). These in vitro studies support recent case study reports of successful therapy using the trimethoprim-sulfamethoxazole combination.
Properties of the Ribosomes of Antibiotic Producers: Effects of Thiostrepton and Micrococcin on the Organisms Which Produce Them
Authors: Dixon Peter D. , Beven Janet E. , Cundliffe Eric
Published: June 2012

Ribosomes of
Streptomyces azureus
, which produces thiostrepton, are resistant to thiostrepton by virtue of being unable to bind the antibiotic. These ribosomes are also resistant to a number of other antibiotics (the thiostrepton group) which may share a common ribosomal binding site and a common mode of action with thiostrepton. Conversely,
Bacillus pumilis
and a strain of micrococcus, which produce the (probably identical) antibiotics micrococcin P and micrococcin, respectively, possess ribosomes which are susceptible to these antibiotics in vitro, although the organisms themselves are resistant.
Activity of Gentamicin, Tobramycin, Polymyxin B, and Colistimethate in Mouse Protection Tests with
Pseudomonas aeruginosa
Authors: Davis Starkey D.
Published: June 2012

Mouse protection tests were carried out with four antibiotics and six strains of
Pseudomonas aeruginosa
. All strains were susceptible to all four antibiotics by an in vitro test. A heavier bacterial inoculum increased the mean effective dose of gentamicin and tobramycin, but not polymyxin B. Second and third doses of gentamicin in the mouse protection test made little change in the mean effective dose. In the mouse protection tests, tobramycin was the most active antibiotic if the results were analyzed in terms of the therapeutic index or ratio of toxicity to efficacy. Colistimethate was poorly inactive in vivo. Polymyxin B was most active on an absolute basis but also was the most toxic. One strain of
Pseudomonas
was classified as resistant to gentamicin in vivo although it was susceptible in vitro. Strains of
Pseudomonas
that were uniformly susceptible to antibiotics in vitro were not uniformly susceptible in the mouse protection test to low doses of antibiotic.
Activity of Minocycline Against
Acinetobacter calcoaceticus
Var.
anitratus
(Syn.
Herellea vaginicola
) and
Serratia Marcescens
Authors: Maderazo Eufronio G. , Quintiliani Richard , Tilton Richard C. , Bartlett Raymond , Joyce Nancy C. , Andriole Vincent T.
Published: June 2012

The activity of minocycline and tetracycline against 23 isolates of
Acinetobacter calcoaceticus
var.
anitratus
(syn.
Herellea vaginicola
) and 178 strains of
Serratia marcescens
was determined by disk and microdilution methods. The results indicate that minocycline is highly active against this species of
Acinetobacter
, all but one strain being inhibited by 0.007 μg of the antibiotic per ml. Tetracycline was also active, though to a lesser degree, against
A. calcoaceticus
. Of the 178 strains of
S. marcescens
tested, only seven (3.9%) had a minimum inhibitory concentration of 2 μg or less of minocycline per ml. Tetracycline was less active than minocycline against
S. marcescens
; with 2 μg of tetracycline per ml, only 2 of 152 (1.3%) strains were inhibited. At concentrations of 8 and 16 μg of minocycline per ml, which can be achieved in the urine with the usual doses, 44.9 and 63.5% of
S. marcescens
strains were inhibited, which implies its possible usefulness for the therapy of urinary tract infection due to this organism.
Rapid Detection of Ampicillin-Resistant
Haemophilus influenzae
and Their Susceptibility to Sixteen Antibiotics
Authors: Kammer Robert B. , Preston David A. , Turner Jan R. , Hawley Lois C.
Published: June 2012

Ampicillin-resistant and -susceptible strains of
Haemophilus influenzae
were tested for susceptibility to 16 antibiotics. Chloramphenicol and a new cephalosporin, cefamandole, were most active with minimal inhibitory concentrations (MICs) for all bacteria tested between 0.5 to 2.0 μg/ml. All but two organisms were susceptible to tetracycline. Ampicillin-resistant strains of
H. influenzae
were less susceptible (MIC, 4 to 32 μg/ml) to carbenicillin and ticarcillin than ampicillin-susceptible organisms (MIC, 0.25 to 1.0 μg/ml). A rapid assay for β-lactamase, utilizing a chromogenic cephalosporin substrate, detected enzyme production in all 17 ampicillin-resistant strains of
H. influenzae
.
Distribution of R Plasmids Among the O-Antigen Types of
Escherichia coli
Isolated from Human and Animal Sources
Authors: Hartley Christine L. , Howe Katherine , Linton A. H. , Linton K. B. , Richmond M. H.
Published: June 2012

The O-antigen types of 600 independently isolated
Escherichia coli
strains from human feces have been determined, and the types have been related to the antibiotic resistance patterns of the strains. The relative abundance of each O-antigen type differed in the susceptible and resistant series of strains. The majority (86%) of the resistant strains carried R plasmids. Resistant
E. coli
(20.3%) were found associated with O-antigen types 8, 9 and 101, whereas the susceptible strains covered a wide range of O-antigen types. Examination of 174 resistant strains isolated from calf feces also showed a prevalence of O-antigen types 8, 9, 101 (24.1%), and it seems probable that strains expressing these three O-antigen types commonly carry R plasmids in the alimentary tracts of man and calves. The number of strains not typeable with the O sera available were similar in the human (12.5%) and the calf (11.5%) series. There are no grounds for distinguishing “human” from “calf”
E. coli
on the basis of their O-antigen reactions.
Bactericidal Activity of Superoxide Anion and of Hydrogen Peroxide: Investigations Employing Dialuric Acid, a Superoxide-Generating Drug
Authors: DeChatelet Lawrence R. , Shirley Pamela S. , Goodson Phillip R. , McCall Charles E.
Published: June 2012

The addition of dialuric acid (a superoxide-generating drug) to a suspension of resting human neutrophils resulted in a stimulation of cellular hexose monophosphate shunt activity. Measurement of oxygen consumption demonstrated a rapid rate of oxygen uptake by the drug alone in aqueous solution. The subsequent addition of catalase (but not of superoxide dismutase) resulted in a substantial release of oxygen, indicating that H
2
O
2
was accumulating in the media. The generation of O
2
−
by the drug was verified by measuring the rate of reduction of cytochrome
c
by the drug in the presence and absence of authentic superoxide dismutase. The growth of
Escherichia coli
B and
Staphylococcus aureus
was inhibited in vitro by addition of the drug to a suitable culture media; the degree of inhibition was dose dependent. This inhibition of bacterial growth could be completely reversed by the addition of as little as 5 μg of purified catalase, but was not affected by concentrations of superoxide dismutase that were 2,000-fold higher. These results suggest that the dialuric acid-induced stimulation of hexose monophosphate shunt activity in neutrophils is due to accumulated H
2
O
2
. Further, the contribution of superoxide to the bactericidal activity towards
E. coli
and
S. aureus
is probably minimal compared with that of H
2
O
2
.
Biosynthesis of Mycophenolic Acid: Purification and Characterization of
S
-Adenosyl-
l
-Methionine:Demethylmycophenolic Acid
O
-Methyltransferase
Authors: Muth W. L. , Nash C. H.
Published: June 2012

The final step in the biosynthesis of mycophenolic acid involves the transfer of a methyl group from
S
-adenosylmethionine to demethylmycophenolic acid. The enzyme,
S
-adenosylmethionine:demethylmycophenolic acid
O
-methyltransferase, was isolated from
Penicillium stoloniferum
and purified 2,700-fold by ammonium sulfate fractionation and diethylaminoethyl-cellulose and Sephadex G-200 chromatography. Maximum enzyme activity was achieved at pH 7.5 and a temperature of 27 to 28 C. The apparent

K
m

for demethylmycophenolic acid was 3.1 × 10
−6
M. The enzyme preparation was 50% inactivated when exposed to 33 C for 15 min. Mycophenolic acid, homocystine,
S
-adenosyl-homocysteine, ethanol, and Mg
2+
inhibited the methyltransferase. This enzyme appears to be subject to end product inhibition which may regulate the synthesis of mycophenolic acid. The methyltransferase activity was highest during the early phases of the fermentation.
Effect of Surfactants on Antibiotic Resistance
Authors: Suling William J. , O'Leary William M.
Published: June 2012

The effectiveness of surfactants as potentiators of antibiotic activity on several resistant strains of bacteria, selected from clinical sources and laboratory collections, was studied using a tube dilution assay. Bacterial strains included members of the
Enterobacteriaceae
and staphylococci. Cetyltrimethylammonium bromide (CTAB), Tween 80 (Tw80), a mixture of
n
-alkyldimethyl betaines (L14), and alpha-(2,4,5-trichlorophenoxy) propionic acid (TCP) were tested in combination with pencillin G (PenG), methicillin (Met), streptomycin (Sm), polymyxin B (PmB), and chlortetracycline (CTC). Growth response to the drug combinations was compared with the response to each drug alone. CTAB and L14 but not Tw80 or TCP were found to potentiate the activity of CTC on strains of
Escherichia coli, Proteus mirabilis
, and
Klebsiella pneumoniae
. Studies on the inhibition of protein synthesis by CTC in cells of a strain of
E. coli
suggested that the surfactants increased the uptake of antibiotic into the cells. CTAB and L14 almost completely sensitized strains of
P. mirabilis, Serratia marcescens, K. pneumoniae
, and
E. coli
to PmB. With the exception of
K. pneumoniae
, TCP was also effective in potentiating the activity of PmB on the above strains whereas Tw80 showed potentiation only with a strain of
E. coli
. CTAB and L14 but not TCP or Tw80 potentiated the activity of PenG but not Met on strains of staphylococci. Studies of penicillinase in the cells suggested that the surfactants inhibited the formation of this enzyme possibly at the level of induction. None of the surfactants were found to potentiate the activity of Sm.
Experimental Keratitis Due to
Pseudomonas aeruginosa:
Model for Evaluation of Antimicrobial Drugs
Authors: Davis Starkey D. , Chandler John W.
Published: June 2012

An improved method for experimental keratitis due to
Pseudomonas aeruginosa
is described. Essential features of the method are use of inbred guinea pigs, intracorneal injection of bacteria, subconjunctival injection of antibiotics, “blind” evaluation of results, and statistical analysis of data. Untreated ocular infections were most severe 5 to 7 days after infection. Sterilized bacterial suspensions caused no abnormalities on day 5. Tobramycin and polymyxin B were more active than gentamicin against two strains of
Pseudomonas
. This model is suitable for many types of quantitative studies on experimental keratitis.
Antibacterial Activity of Tropilidine and Tropone
Authors: Trust T. J. , Bartlett Karen H.
Published: June 2012

The seven-membered ring compounds tropilidine and tropone were shown to be bacteriostatic and bactericidal for a wide range of bacterial species.
Vestibular Reactions Associated with Minocycline
Authors: Jacobson Jay A. , Daniel Brenda
Published: June 2012

Several recent reports have indicated that minocycline, a drug effective for meningococcal disease prophylaxis, is associated with a high incidence of vestibular side effects. In January 1975, a questionnaire on adverse reactions was completed by all 29 staff members of a North Georgia hospital who had taken minocycline at the recommended dosage after exposure to a suspected meningococcal meningitis case and by 25 age-, sex-, and occupation-matched non-treated controls. In the treated group 86% experienced moderate to severe vestibular symptoms; 84% of the symptomatic persons experienced their onset after one or two doses of 100 mg. Fifty-two percent of the treated staff members stopped taking the medication because of these effects. The symptoms resolved within 48 h after affected persons discontinued the medication. Until the safety of minocycline can be reestablished, rifampin is recommended for meningococcal disease prophylaxis, and alternative drugs are encouraged for other indications.
Efficacy of 9-β-
d
-Arabinofuranosylhypoxanthine 5′-Monophosphate in Therapy of Equine Abortion Virus-Induced Hepatitis in Hamsters
Authors: Allen Lois B. , Huffman John H. , Revankar Ganapathi R. , Tolman Robert L. , Simon Lionel N. , Robins Roland K. , Sidwell Robert W.
Published: June 2012

Equine abortion virus (EAV)-induced hepatitis in hamsters presents an interesting animal model for the evaluation of drugs possessing anti-deoxyribonucleic acid virus activity. These experiments demonstrate that 9-β-
d
-arabinofuranosylhypoxanthine 5′-monophosphate (ara-HxMP), a new synthetic, water-soluble, antiviral agent, effectively controls this disease in hamsters with a therapeutic index of ∼60. Ara-HxMP prevented hepatitis-associated deaths in hamsters, reduced the titer of EAV developing in hamsters, and inhibited the increase of serum glutamic pyruvic transaminase in EAV-infected hamsters.
Inhibition of Vesicular Stomatitis Virus Replication by Poly(2′-Fluoro-2′-Deoxyuridylic Acid)
Authors: Grosch Josephine C. , Erickson Robert J.
Published: June 2012

Poly(2′-fluoro-2′-deoxyuridylic acid) is known to be an effective inhibitor of the deoxyribonucleic acid polymerase found within the oncornaviruses. This synthetic polynucleotide was found to inhibit the replication of vesicular stomatitis virus in mouse L cells. The polymer was shown to be capable of inhibiting the viral ribonucleic acid (RNA)-dependent RNA polymerase, and it is proposed that this is the mechanism of antiviral activity. The following observations support this viewpoint: (i) the polymer is most active when added after virus adsorption; (ii) the antiviral activity is not species specific; and (iii) the polynucleotide is nontoxic to the host cell. Conventional methodologies designed to increase nucleic acid uptake by cultured cells do not show an increase in antiviral potency.
Rifampin Susceptibility of Ribonucleic Acid Synthesis in a Fragile
Saccharomyces cerevisiae
Mutant
Authors: Venkov P. V. , Milchev G. I. , Hadjiolov A. A.
Published: June 2012

Ribonucleic acid (RNA) synthesis in the sorbitol-dependent, fragile yeast mutant VY1160 (Venkov et al., 1974) is rapidly inhibited by rifampin. The growth of the mutant cells and protein synthesis are more slowly affected by the antibiotic, apparently as secondary phenomena. Lower doses of rifampin (50 to 100 μg/ml) preferentially inhibit ribosomal RNA synthesis in comparison to that of messenger RNA and transfer RNA. Transcription and translation of messenger RNA continues in the presence of low doses of rifampin, as evidenced by the unimpaired induction of α-glucosidase. Partially purified RNA polymerase II from this mutant, in contrast to that from the parental strain, is strongly inhibited by low concentrations (1 μg/ml) of rifampin, whereas RNA polymerase I from the two strains is similar in behavior. The mutant may be useful for the study of regulatory mechanisms of transcription in eukaryotes.
Influences of Media and Inocula on the In Vitro Susceptibility of
Haemophilus influenzae
to Co-Trimoxazole, Ampicillin, Penicillin, and Chloramphenicol
Authors: Marks Melvin I. , Weinmaster Gerry
Published: June 2012

The effects of inocula and media on the activities of ampicillin, penicillin, chloramphenicol and co-trimoxazole against
Haemophilus influenzae
were examined in vitro. Two inocula and four media were tested by the disk diffusion, broth dilution, and agar dilution methods. Chloramphenicol activity versus
H. influenzae
was least affected by changes in inocula and media, whereas co-trimoxazole was most susceptible to these effects. Filde's and Levinthal's agar dilution tests were most satisfactory for ampicillin. Penicillin was less active on Levinthal's than on Filde's agar. Both ampicillin and penicillin were less active when tested against the higher inoculum. Co-trimoxazole was most active (<1%
H. influenzae
was resistant) when tested at an inoculum of 10
6
colony-forming units/ml on diagnostic susceptibility test agar with 5% lysed horse blood added. The majority of
H. influenzae
appeared resistant to co-trimoxazole with increases in the test inocula and/or when tested on brain heart infusion with Filde's, Levinthal's or “low-thymidine” Mueller-Hinton medium.
Bactericidal Activity of Combinations of Penicillin or Clindamycin with Gentamicin or Streptomycin Against Species of Viridans Streptococci
Authors: Duperval Raymond , Bill Nancy J. , Geraci Joseph E. , Washington John A.
Published: June 2012

Checkerboard bactericidal studies were performed with two strains each of
Streptococcus mitis, S. salivarius
, and
S. sanguis
, and the results were analyzed by the use of isobolograms. Synergy between penicillin and streptomycin or gentamicin was demonstrated with four strains, representing two of
S. salivarius
, one of
S. sanguis
, and one of
S. mitis
; the remainder were either too susceptible or too resistant to be analyzed. Clindamycin with streptomycin or gentamicin acted synergistically with three strains, representing two of
S. sanguis
and one of
S. salivarius
; the remainder were either too susceptible or too resistant to be analyzed.
Prospective Double-Blind Evaluation of Topical Adenine Arabinoside in Male Herpes Progenitalis
Authors: Goodman Edward L. , Luby James P. , Johnson M. Tracy
Published: June 2012

Thirty-four virologically proven episodes of herpes progenitalis in 32 men were treated in a prospective double-blind study with either adenine arabinoside ointment or an identical-appearing placebo for 7 days. Clinical evaluation and quantitative virological studies were done on days 1, 3, and 8. There was a highly significant correlation between clinical response and quantitative virology. There was no difference in clinical or virological response between drug and control groups. Primary attacks tended to have higher viral excretion over the period of observation. The level of complement-fixing antibody to herpes simplex virus type 2(<1:16 versus ≥1:16) in patients with recurrent disease did not appear to alter the course of viral excretion.
Relation Between Lipophilicity and Pharmacological Behavior of Minocycline, Doxycycline, Tetracycline, and Oxytetracycline in Dogs
Authors: Barza Michael , Brown Richard B. , Shanks Carolyn , Gamble Charles , Weinstein Louis
Published: June 2012

Four tetracyclines were studied in dogs to determine the relation between their lipophilicity and various other pharmacological characteristics. Lipid solubility correlated inversely with the mean concentration of drug in arterial plasma and renal uptake and excretion, and directly with the biliary concentration gradient (level in bile/level of free drug in serum). Only the more lipophilic congeners minocycline and doxycycline passed the blood-brain and blood-ocular barriers in detectable concentrations. Mean levels of minocycline in the brain exceeded those of doxycycline by almost threefold; the difference was of borderline statistical significance (
P
= 0.05 to 0.1). Lipophilicity correlated inversely with the concentration of antibiotic in renal medulla but not in renal cortex or in the liver. When intestinal loops containing saline, milk, or 10% Gelusil were studied, the only combination exhibiting striking intraluminal accumulation was doxycycline in milk. These results indicate that lipophilicity correlates with many, but not all, of the transport characteristics of tetracycline antibiotics.
Biosynthesis of Puromycin in
Streptomyces alboniger
: Regulation and Properties of
O
-Demethylpuromycin
O
-Methyltransferase
Authors: Sankaran L. , Pogell Burton M.
Published: June 2012

Mechanisms for regulation of puromycin biosynthesis in
Streptomyces alboniger
were studied by measuring the levels of
S
-adenosyl-
l
-methionine:
O
-demethylpuromycin
O
-methyltransferase. The enzyme was released in soluble form from mycelia by 3 to 5 min of sonication at 4 C. Maximal specific activities of 0.7 and 0.1 nmol/min per mg of protein were found in cells grown in corn steep liquor-corn starch and Hickey-Tresner media, respectively. In both media, the
O
-methyltransferase activity rose from low levels to a maximum during midlogarithmic growth and then declined or disappeared completely (in Hickey-Tresner medium) during stationary phase. Either glucose (1%) or ethidium bromide (5 μM) reduced
O
-methyltransferase formation to very low levels with no effect on overall growth. Complete glucose repression of antibiotic formation occurred on agar. Cells grown in the presence of ethidium bromide continued to produce low enzyme levels after regrowth in the absence of dye, but formed normal amounts of puromycin on Hickey-Tresner agar. The
O
-methyltransferase, either crude or purified, was rapidly inactivated at 37 C. Each substrate alone, or both together at lower concentrations, protected against this loss of activity. Puromycin inhibited the transferase. Regulation of
O
-methyltransferase synthesis in
S. alboniger
includes (i) induction early in growth that is susceptible to catabolite repression and differential inhibition by ethidium bromide, and (ii) protection of the enzyme from inactivation by increased intracellular levels of its substrates. The
O
-methyltransferase was purified 30- to 40-fold by a combination of protamine sulfate precipitation, ammonium sulfate fractionation, adsorption and gradient salt elution from diethylaminoethyl-cellulose and Sephadex G-200 gel filtration. The enzyme was very unstable, even at low temperatures, upon purification beyond the salt fractionation step, but was stabilized by the addition of
S
-adenosyl-
l
-methionine during later stages of purification.
Antimicrobial Effect of Simple Lipids and the Effect of pH and Positive Ions
Authors: Larsson Kåre , Norén Börje , Odham Göran
Published: June 2012

Various branched fatty acids, particularly those of
iso
-configuration, have been shown to possess fungistatic and bacteriostatic properties. On the basis of their swelling effect on hyphae of
Fusarium roseum
it was suggested that this is due to an increase in the permeability of the plasma membrane. The solubilization of fatty acids in membranes should be expected to be influenced by the degree of dissociation and the presence of counter ions. Therefore, the effects of pH and K
+
, Na
+
, and Ca
2+
ions were studied. It is demonstrated that the presence of the univalent ions, Na
+
and K
+
, markedly enhances the fungistatic effect of
iso
-tetradecanoic acid, whereas the opposite effect is noted for the divalent ion, Ca
2+
. The effects are particularly pronounced at high pH. Furthermore, the antimicrobial effect obtained from the combination of fatty acid and tetramethylthiuramdisulfide is significantly enhanced in the presence of 0.1 and 0.2% KCl.
Antimicrobial Effect of Simple Lipids with Different Branches at the Methyl End Group
Authors: Larsson Kåre , Norén Börje , Odham Göran
Published: June 2012

Various fatty acids of branched nature possess fungistatic and bacteriostatic properties. Some of these, particularly those of
iso
-configuration, strongly enhance the effect of conventional antimicrobial agents that act inside the cell membrane. A relation between this biological effect and the collapse properties of the corresponding monomolecular surface film on water has been observed. In this work, a series of fatty acids with a slightly smaller end group than
iso
-propyl, the ω-cyclopropane fatty acids, as well as one possessing a somewhat larger end group, the
neo
-branched fatty acids, have been examined. The ω-cyclopropane fatty acids were found to be more fungistatic than the
iso
-acids studied earlier. Furthermore, both cyclopropane and
neo
-fatty acids of short chain lengths exhibited synergistic effects in combination with tetramethylthiuramdisulfide.
Antibacterial Action of Primaquine: Effects In Vitro on Polypeptide Synthesis and In Vivo on Ribosomes and Ribosomal Ribonucleic Acid
Authors: Olenick John G.
Published: June 2012

Primaquine inhibited polyphenylalanine formation directed by poly(U) in a cell-free system obtained from
Bacillus megaterium
only when the drug was preincubated with transfer ribonucleic acid (tRNA), poly(U), or ribosomes. Considerably less inhibition was produced when the ionic strength of the preincubation mixture of tRNA or poly(U) plus primaquine was increased; with ribosomes, the extent of inhibition was only slightly reduced. In cultures of
B. megaterium
, primaquine induced the breakdown of ribosomes and their RNA.
Hyperbaric Oxygen Exposures for Intrahepatic Abscesses Produced in Mice by Nonsporeforming Anaerobic Bacteria
Authors: Hill Gale B.
Published: June 2012

Hyperbaric oxygen exposures were evaluated for treatment of progressive liver abscesses produced by intraperitoneal injection of combined cultures of
Fusobacterium necrophorum
plus either
Bacteroides fragilis
subsp.
fragilis
or
Fusobacterium nucleatum
in a mouse model. Infected control and hyperbaric oxygen-exposed mice were autopsied 5 or 6 weeks after inoculation of bacteria and were assigned numerical pathology scores according to the number and size of abscesses present. Seventeen daily 3-h exposures to 100% O
2
at 2 atmospheres absolute pressure begun either 1 day or 1 week after injection of bacteria significantly reduced the number and size of abscesses among mice infected with either mixture of anaerobic organisms. Abscesses due to mixed fusobacteria were often completely resolved. These data support the efficacy of hyperbaric oxygen for treatment of mixed anaerobic infection produced by
Bacteroides
and
Fusobacterium
species and suggest its further evaluation as a potential alternate or adjunct to present therapy for certain types of serious anaerobic infection.
Beta-Indoleethanol and Beta-Indolelactic Acid Production by
Candida
Species: Their Antibacterial and Autoantibiotic Action
Authors: Narayanan T. K. , Rao G. Ramananda
Published: June 2012

Candida
spp. grown in synthetic medium supplemented with
l
-tryptophan as sole nitrogen source produced β-indoleethanol (β-IEA) and β-indolelactic acid (β-ILA). These compounds isolated from the culture filtrates were characterized by ultraviolet, infrared, and nuclear magnetic resonance spectral studies. Using
dl
-[
3
H]trypotophan in the medium, labeled β-IEA and β-ILA were isolated. Further, β-IEA was produced as a result incubating log-phase cells of
C. albicans
with β-ILA. Both β-IEA and β-ILA inhibited the growth of gram-positive and -negative bacteria. Autoantibiotic action of these compounds on
Candida
spp. and the reversal of this inhibition were studied.
In Vitro Activity, Synergism, and Testing Parameters of Amikacin, with Comparisons to Other Aminoglycoside Antibiotics
Authors: Kelly Michael T. , Matsen John M.
Published: June 2012

The activity of the new aminoglycoside antibiotic, amikacin, was evaluated in vitro against 219 clinical bacterial isolates. One hundred eighty-nine of the 219 strains had agar dilution minimal inhibitory concentration values of 8.0 μg/ml or less for amikacin. Comparative agar dilution studies were performed for gentamicin, kanamycin, and tobramycin. Gentamicin was the most active overall, but tobramycin and amikacin also had significant activity against most bacterial groups. The effects of divalent cations on the susceptibility of
Pseudomonas aeruginosa
to amikacin were evaluated, and the minimal inhibitory concentration values varied sixfold over a range of divalent cation concentrations from 0.2 to 8.75 mg%. The effects of media and inoculum size on disk susceptibility testing with amikacin were also evaluated. In addition, a synergistic interaction between carbenicillin and amikacin against
P. aeruginosa
was demonstrated. Amikacin appears to be a promising new broad spectrum antimicrobial agent.
Effect of Cytosine Arabinoside and 5-Iodo-2′-Deoxyuridine on a Cytomegalovirus Infection in Newborn Mice
Authors: Kelsey Douglas K. , Kern Earl R. , Overall James C. , Glasgow Lowell A.
Published: June 2012

Murine cytomegalovirus was inhibited by 0.6 to 1.2 μg of cytosine arabinoside per ml and by 0.3 to 0.6 μg of 5-iodo-2′-deoxyuridine in mouse embryo fibroblast cells. Human cytomegalovirus was inhibited by similar concentrations of the two drugs in WI-38 cells. Intraperitoneal inoculation of suckling mice with 10
4.5
plaque-forming units of murine cytomegalovirus provides a model for disseminated human cytomegalovirus infection in human newborn infants and is characterized by a widespread infection involving the liver, spleen, lung, kidney, and brain with a 70 to 90% mortality in 7 to 9 days. Treatment with 12.5 mg of cytosine arabinoside per kg or 25 mg of 5-iodo-2′-deoxyuridine per kg twice daily for 8 days had no effect on final mortality or the pathogenesis of the infection with the exception of reduced viral titers in the spleen of 5-iodo-2′-deoxyuridine-treated animals. These data indicate that neither cytosine arabinoside nor 5-iodo-2′-deoxyuridine are effective in the treatment of murine cytomegalovirus infections in suckling mice and suggest that they may be of limited value in the treatment of severe cytomegalovirus infections in human neonates.
Antibiotic Susceptibility of the Subspecies of
Bacteroides fragilis
Authors: Blazevic Donna J.
Published: June 2012

Strains (115) of
Bacteroides fragilis
were identified at the subspecific level and were tested for susceptibility to ampicillin, cephalothin, chloramphenicol, clindamycin, penicillin, and tetracycline using an agar dilution technique. We tested the following strains:
B. fragilis
subsp.
distasonis
, 12;
B. fragilis
subsp.
fragilis
, 39;
B. fragilis
subsp.
ovatus
, 10;
B. fragilis
subsp.
thetaiotaomicron
, 32;
B. fragilis
subsp.
vulgatus
, 10; and
B. fragilis
subsp. “other,” 12. There were no marked differences in susceptibility between the subspecies. One strain of
B. fragilis
subsp.
thetaiotaomicron
had a minimal inhibitory concentration of 12.5 μg/ml for clindamycin, but all other strains were susceptible. All the strains were susceptible to chloramphenicol. Susceptibility to tetracycline was variable. Only a few strains were susceptible to the penicillins and cephalothin.