bluuebunny/crossref_metadata_2025 huggingface dataset:
Herpesvirus hominis
Infection in Newborn Mice: Treatment with Interferon Inducer Polyinosinic-Polycytidylic Acid
Authors: Kern Earl R. , Overall James C. , Glasgow Lowell A.
Published: June 2012

Intranasal inoculation of newborn mice with
Herpesvirus hominis
(HVH) type 2 provides a model for disseminated herpesvirus infections of human newborn infants. Treatment of this experimental infection with polyinosinic-polycytidylic acid [poly(I:C)] significantly increased the mean survival time and markedly altered the pathogenesis of the infection. No significant protection against final mortality was observed. Poly(I:C) therapy completely inhibited detectable viral replication in all target organs tested except the brain. In the brain there was a 2-day delay in the onset of viral replication in treated animals, which correlated with the 1- to 2-day increase in mean survival time. In general, the control of HVH replication occurred in those target organs in which poly(I:C)-induced interferon was detectable. The failure of poly(I:C) to alter the final mortality of newborn mice infected with HVH appears to be primarily due to the lack of sufficient levels of interferon induced in brain tissue and the failure to prevent viral replication in this critical target organ.
Effects of
cis
-Dichlorodiammineplatinum (II) and Related Transition Metal Complexes on
Escherichia coli
Authors: Monti-Bragadin C. , Ramani L. , Samer L. , Mestroni G. , Zassinovich G.
Published: June 2012

A number of transition metal complexes, including the
cis
and
trans
isomers of dichlorodiammineplatinum (II), six complexes of rhodium (I), two of iridium (I), and one of ruthenium (II) have been tested for their ability to induce lambda prophage, to produce filamentous growth of
Escherichia coli
, and to be selectively toxic for strains with defects in the deoxyribonucleic acid repair system. Dichlorotetrakis(dimethylsulfoxide)ruthenium II [RuCl
2
(DMSO)
4
] was strictly similar to
cis
-dichlorodiammineplatinum II [
cis
PtCl
2
(NH
3
)
2
] in the test for lambda induction, filamentous growth production, and selective toxicity for a
recA
−
strain. [Rh COD 1,10-phenanthroline]
+
Cl
−
, though more toxic for
recA
−
than for
rec
+
E. coli
, was scarcely effective in the test for filamentous growth and did not induce prophage. None of the other tested compounds showed any similarity with
cis
-PtCl
2
(NH
3
)
2
. Due to the interesting results obtained with
cis
-PtCl
2
(NH
3
)
2
as an antitumor agent, it seems reasonable to propose RuCl
2
(DMSO)
4
as a potential antitumor substance.
Antimicrobial Resistance of Shigella Isolated in New York City in 1973
Authors: Neu Harold C. , Cherubin Charles E. , Longo Elaine D. , Winter Joseph
Published: June 2012

One hundred and two
Shigella sonnei
and fourteen
S. flexneri
strains isolated from individual patients in New York City hospitals were investigated for antibiotic resistance. The
S. sonnei
showed 60% resistance to ampicillin and 58% to tetracycline and streptomycin.
S. flexneri
showed no ampicillin resistance but 50% resistance to tetracycline. There were marked differences in resistance of
S. sonnei
between hospitals which were not explainable by ethnic or socio-economic differences in the patient populations.
Cycloheximide Production by
Streptomyces griseus
: Alleviation of End-Product Inhibition by Dialysis-Extraction Fermentation
Authors: Kominek L. A.
Published: June 2012

The use of dialysis fermentation with the continuous extraction of the dialysate has resulted in a twofold increase in the cycloheximide titer due to relief from product inhibition. Continuous extraction of the dialysate has eliminated the necessity for large reservoir volumes of fermentation medium normally used in dialysis fermentation. The apparatus used in this procedure is described.
New Method for Susceptibility Testing with Antifungal Agents
Authors: Wagner Gerald , Shadomy Smith , Paxton Larry D. , Espinel-Ingroff Ana
Published: June 2012

A new method for the determination of minimal inhibitory and fungicidal concentrations of antifungal agents for filamentous fungi is described. 5-Fluorocytosine (5-FC) was used as a representative agent and was tested against the following genera:
Allescheria, Aspergillus, Cladosporium, Fonsecaea
, and
Phialophora
. 5-FC was found to be inhibitory but not fungicidal for many of the fungi tested, including eight of clinical origin.
Detection of Agents That Alter the Bacterial Cell Surface
Authors: Sud Inder Jit , Feingold David S.
Published: June 2012

Proteus mirabilis
is not killed by polymyxin B, normal serum, or sodium deoxycholate. Exposure to polymyxin B renders the cells susceptible to killing by the latter two agents. The data suggest that this synergism is due to polymyxin B-induced surface changes. The results point out an inadequacy of existing methods of screening for antibiotics; they fail to detect agents which, while showing no in vitro effect on growth, may alter a resistant organism so that it becomes more susceptible to other antimicrobials or host defense mechanisms. A method is described which can be used to detect such cell surface-modifying agents.
Analysis of Rifampin Disk Diffusion and Stability in 7H10 Agar
Authors: Bonalsky J. R. , Jaconia D. , Konopka E. A. , Adair F. W.
Published: June 2012

Rifampin was incorporated into Middlebrook 7H10 medium either by adding an aliquot of the antibiotic into melted agar (final concentration 1.0 and 3.0 μg/ml) or by submerging a 5 or 15 μg of rifampin paper disk into 5 ml of melted agar contained in one quadrant of a Felson “X” plate. At intervals, plugs of agar were removed from the stored plates and assayed. Plates stored at 5 C for 28 days showed no loss of potency; at 37 C, the half-life of rifampin was 9 days. Stability of rifampin at these concentrations in 7H10 medium was independent of the method used for incorporation. Using the disk method, uniform rifampin concentrations of 0.75 μg/ml on day 5 for the 5-μg disk and 2.7 μg/ml on day 6 for the 15-μg disk were observed. Results indicated that the rifampin concentrations within the agar dilution and disk diffusion plates were equivalent at these times.
Inactivation of Myxoviruses by Calcium Elenolate
Authors: Renis Harold E.
Published: June 2012

Calcium elenolate inactivates all myxoviruses so far tested. The pH of the reaction mixture is less critical for myxovirus inactivation than that required for coxsackie A-21 virus; the myxoviruses are inactivated at a broad spectrum of pH with the maximum activity occurring at a pH below 7.0. The infectivity of the virus is more susceptible to the action of calcium elenolate than is either the neuraminidase activity or the hemagglutinin. The inactivation of Newcastle disease virus by calcium elenolate also destroys the ability of the virus to induce interferon formation in cell culture and in mice.
Inhibition of De Novo Fatty Acid Synthesis by the Antibiotic Cerulenin in
Bacillus subtilis
: Effects on Citrate-Mg
2+
Transport and Synthesis of Macromolecules
Authors: Wille Wolfgang , Eisenstadt Eric , Willecke Klaus
Published: June 2012

Inhibition of de novo fatty acid biosynthesis by the antibiotic cerulenin in
Bacillus subtilis
stopped de novo synthesis of neutral lipids and phospholipids. The bacteria ceased growing but remained completely viable. Addition of 12-methyltetradecanoic acid and palmitic acid to the culture medium of cerulenin-treated cells restored growth of the bacteria, albeit at a reduced rate. Although the de novo synthesis of all lipid components of the membrane was blocked, citrate-Mg
2+
transport activity remained inducible, and induced cells did not lose this transport activity when treated with cerulenin. Shortly after the addition of cerulenin, the rate of ribonucleic acid synthesis dropped rapidly and was followed by a slower decrease in the rate of protein synthesis. The rate of deoxyribonucleic acid synthesis remained almost unaffected. The rapid decrease of ribonucleic acid synthesis in cerulenin-treated cells might be due to the inhibition of de novo fatty acid biosynthesis or it might be due to a secondary effect of cerulenin in
B. subtilis
cells.
Preparation and Properties of a Cephalosporin Acetylesterase Adsorbed onto Bentonite
Authors: Abbott Bernard J. , Fukuda D. S.
Published: June 2012

A cephalosporin acetylesterase produced by
Bacillus subtilis
was immobilized by adsorption onto bentonite. The immobilized enzyme (E
I
) and the soluble enzyme (E
S
) exhibited Michaelis-Menton kinetics with 7-aminocephalosporanic acid (7-ACA):

K
m

= 2.8 × 10
−3
M and

K
m

= 3.2 × 10
−3
M, respectively. Similar kinetics were observed with 7-(thiophene-2-acetamido)cephalosporanic acid (cephalothin), but the

K
m

value measured with E
I
(3.7 × 10
−3
M) was less than one-half that measured with this substrate and E
S
. The reduction in

K
m

value was correlated with the ability of bentonite to adsorb cephalothin. The reaction products, acetate and deacetyl-7-ACA, were weak competitive inhibitors of E
S
and E
I
. The

K
i

values for E
I
were 5.0 × 10
−2
M for acetate and 3.6 × 10
−2
M for deacetyl-7-ACA. Similar values were measured with E
S
and these substrates. E
I
retained about 80% of its initial activity after 3 weeks of storage in solution at 25 C. However, the enzyme dissociated from the bentonite particles during the deacetylation reaction. This dissociation was minimized by cross-linking E
I
with glutaraldehyde or bis-dimethyladipimidate, or by adding Al(OH)
3
to the suspension. With the latter addition, E
I
was stabilized so that it could be reused nine times before one-half of the initial activity was lost.
Comparative Clinical Pharmacology of Gentamicin, Sisomicin, and Tobramycin
Authors: Lode H. , Kemmerich B. , Koeppe P.
Published: June 2012

Using a randomized crossover design involving 12 normal subjects, we studied comparatively the pharmacokinetics and tolerance of three aminoglycoside antibiotics, gentamicin, sisomicin, and tobramycin. Serum concentrations were determined during 8 h and the urine recovery rate was determined within 24 h after a 1-h intravenous infusion of the respective antibiotic in a dose of 1 mg/kg of body weight. Microbiological assay was performed with the agar diffusion test (
Bacillus subtilis
); pharmacokinetic calculations were performed by means of a digital computer on the basis of a mathematical model of an open, two-compartment system. Of the three antibiotics studied, gentamicin showed the lowest concentration in serum after termination of the 1-h infusion (3.85 ± 0.67 μg/ml), and the serum-regression curve steadily lay below those of the two other antibiotics. Sisomicin had the highest serum concentrations (4,66 ± 1.24 μg/ml) and the serum-level curve exceeded that of the two other antibiotics. Tobramycin occupied a position between sisomicin and gentamicin in form of its serum level characteristics. Corresponding to the serum kinetics we also found slight differences in the pharmacokinetic parameters, especially in serum half-lives, elimination constants, and areas under the serum level curves. The test of liver and kidney functions and the hematological systems, as well as the function of the stato-acusticus nerve, showed no pathological changes by any of the three antibiotics tested.
Prospective Comparative Study of Variable Dosage and Variable Frequency Regimens for Administration of Gentamicin
Authors: Goodman Edward L. , Van Gelder James , Holmes Randall , Hull Alan R. , Sanford Jay P.
Published: June 2012

In patients with impaired renal function, careful adjustment of gentamicin dosage is required to achieve therapeutic yet nontoxic concentrations. Two regimens that differ in pharmacodynamic characteristics have been recommended for this purpose: prolonging the intervals between administration of equal doses (variable frequency regimen [VFR]) or administering a loading dose followed at the usual intervals by reduced maintenance doses (variable dosage regimen [VDR]). These regimens were compared in a prospective, randomized study of 20 seriously ill hospitalized patients, 10 on VFR and 10 on VDR. Wide variability in peak serum levels of gentamicin was observed both between patients and in individual patients after separate injections of the same dosage. As predicted by the design of these regimens, the trough serum levels of gentamicin correlated significantly with the serum creatinine concentrations in patients on the VDR but not in patients on the VFR. A gentamicin trough level of ≥4 μg/ml was the only variable among those tested that correlated significantly with development or progression of renal insufficiency during treatment with gentamicin, but such trough levels were observed frequently on both regimens. Whereas this study does not permit a direct comparison of the therapeutic efficacy of VDR and VFR, no difference in the risk of nephrotoxicity with these regimens was observed.
Chloramphenicol Binding Site with Analogues of Chloramphenicol and Puromycin
Authors: Vince Robert , Almquist Ronald G. , Ritter Clare L. , Daluge Susan
Published: June 2012

The effect of a series of puromycin analogues and aminoacyl chloramphenicol derivatives on poly(U,C)-directed polyphenylalanine synthesis in an
Escherichia coli
cell-free system was examined. A comparison between the structures and activities of the puromycin and chloramphenicol analogues was made to examine the proposal that ribosomal binding sites for both antibiotics overlap. Our results suggest that the dichloroacetamido group in the chloramphenicol molecule does not correspond to the role of the aminoacyl moieties of either puromycin or aminoacyl transfer ribonucleic acid. These results comparing the structures and activities of puromycin and chloramphenicol analogues also seem inconsistent with a common binding site for the
p
-substituted phenyl moieties of the two antibiotics. Previous data have indicated that both sites are mutually affected by the prior binding of either antibiotic. Although it is possible that chloramphenicol and puromycin may have overlapping bindings sites, no common structural features between the two antibiotics are supported by our data.
Response of Yeast and Mycelial Phases of
Histoplasma capsulatum
to Amphotericin B and Actinomycin D
Authors: Cheung S. C. , Medoff G. , Schlessinger D. , Kobayashi G. S.
Published: June 2012

The dimorphic fungus
Histoplasma capsulatum
exists in two phases: a unicellular yeast form at 37 C and a mycelium at 25 C. We have found that these two phases have selective drug susceptibilities. The mycelial form of
H. capsulatum
was much more susceptible to the polyene antibiotic amphotericin B than the yeast form; in contrast, the yeast form was more susceptible to the antibiotic actinomycin D. The changes in susceptibility occurred early in the transition between the two phases and permitted the transitions to be blocked by sublethal concentrations of the appropriate drugs.
Triethyl-
n
-Hexylammonium Triethyl-
n
-Hexylboride: a New Antimicrobial Showing Activity Against
Candida albicans
and Gram-Positive Bacteria
Authors: Rosenthal K. S. , Storm D. R. , Ford W. T.
Published: June 2012

The organic salt triethyl-
n
-hexylammonium triethyl-
n
-hexylboride (N
2226
B
2226
) has biostatic effects against two gram-positive bacteria,
Bacillus subtilis
and
Micrococcus luteus
, and the yeast
Candida albicans. Escherichia coli
and chicken embryo fibroblasts grown in tissue culture are more refractory to this compound.
Lactulose Therapy in Shigella Carrier State and Acute Dysentery
Authors: Levine Myron M. , Hornick Richard B.
Published: June 2012

Antibiotic-resistant shigella are increasingly prevalent. Lactulose, a non-absorbable disaccharide, was investigated as an alternative therapy for shigella infection on the hypothesis that the short-chain fatty acids (inhibitory to shigella) resulting from metabolism of lactulose by normal colonic flora would diminish shigella excretion. A long-term antibiotic-refractory carrier (large bowel) excreting 10
4
to 10
7
Shigella sonnei
/g of feces was given two courses of lactulose (of 24 and 16 days duration). During lactulose therapy, excretion of shigella was greatly diminished (24-day course) or suppressed below detectable levels (16-day course), but returned to pretreatment levels upon discontinuation of lactulose. The volunteers who developed induced shigellosis during an efficacy test of oral
Shigella flexneri
2a vaccine were randomly given oral ampicillin, lactulose, or placebo in double-blind fashion. Daily rectal cultures were taken. After 4 days of therapy, cultures were still positive in four out of four men on lactulose, three of three on placebo and none of three on ampicillin. Mean stool pH of men receiving lactulose (6.1) was significantly lower than those getting ampicillin (7.4),
P
< 0.01, or placebo (7.0),
P
< 0.05. Only in the lactulose group was mean stool pH during therapy significantly decreased compared with the level off therapy (6.1 versus 7.1),
P
< 0.02. Lactulose shows promise for the treatment of shigella carriers but appears ineffective in treatment of acute shigellosis.
In Vitro Susceptibility of Selected Bacteria to Three Diphosphonia Heterocyclic Compounds
Authors: Pearson Frederick C. , Lemeshka Theodore , Ferrara Frank , Williams John C.
Published: June 2012

The antibacterial activity of 1,1,4,4-tetraphenyl-1,4-diphosphonia-2,5-diphenylcyclohexadi-2,5-ene dichloride and two of its derivatives were screened for activity using the disk method. All derivatives exhibited antibacterial activity against gram-positive organisms tested, but little inhibition of gram-negative species was noted.
Stability of Frozen Rat Plasma Containing Different Antibiotics
Authors: Berti Maria A. , Maccari Mario
Published: June 2012

The antibiotic activity was determined at different intervals of time on plasma samples, taken from rats treated with a certain number of commonly used antibiotics, and kept at −20 C up to 8 weeks. The results of the microbiological assays demonstrate that the stability of the antibiotics in the frozen plasma decreases in the following order: oxytetracycline > cephalexin, streptomycin, erythromycin > demeclocycline > ampicillin, amoxycillin > penicillin G, cephaloridine, rolitetracycline, and tetracycline.
Presence of δ-(
l
-α-Aminoadipyl)-
l
-Cysteinyl-
d
-Valine in Fermentations of
Penicillium chrysogenum
Authors: Adriaens P. , Meesschaert B. , Wuyts W. , Vanderhaeghe H. , Eyssen H.
Published: June 2012

Cultures of
Penicillium chrysogenum
, growth with [
35
S]sulfate or labeled amino acids, were examined by ion-exchange chromatography for possible peptidic precursors of penicillin. A sulfur-containing compound, present in both the mycelial extracts and the culture filtrates, was eluted at the location of the synthetic
lld
-tripeptide δ-(
l
-α-aminoadipyl)-
l
-cysteinyl-
d
-valine. Since this compound was also labeled when the cultures were incubated with
dl
-[6-
14
C]α-aminoadipic acid,
l
-[3,3′-
3
H]cystine, or
dl
-[1-
14
C]valine, its identity with the synthetic
lld
-tripeptide can be accepted. No δ-(
l
-α-aminoadipyl)-
l
-cysteine or
lll
-tripeptide were detected. The implications of these findings for tripeptide and penicillin biosynthesis are discussed.
Genetic and Biochemical Characterization of a Ribosomal Mutant of
Bacillus subtilis
Resistant to Sporangiomycin
Authors: Bazzicalupo M. , Parisi B. , Pirali G. , Polsinelli M. , Sala F.
Published: June 2012

The antibiotic sporangiomycin affects the growth of
Bacillus subtilis
by inhibiting protein synthesis. Mutants of
B. subtilis
resistant to sporangiomycin have been isolated. One of these, PB 1690, has been further studied. The analysis of subcellular fractions from the mutant has shown that the biochemical effect of the mutation is an alteration of a site on the 50
S
ribosomal subunit responsible for the binding of the antibiotic: the mutant ribosomes do not bind sporangiomycin and are capable of carrying out phenylalanine polymerization in the presence of sporangiomycin. The resistance mutation maps on the chromosomal region where the ribosomal markers map. The mutant strain is also resistant to the action of the chemically related antibiotic thiostrepton. Treatment of
B. subtilis
ribosomes with LiCl results in the detachment of a group of proteins including the one responsible for sporangiomycin resistance. Active ribosomes can be reconstructed by mixing “split proteins” and “core particles” of either parental or mutant origin. The fate of the mutant protein can now be followed by assaying reconstructed ribosomes for capacity to bind sporangiomycin and for resistance to the action of the antibiotic in the reactions for phenylalanine polymerization.
Comparison of the Antibacterial Activities of Sisomicin and Gentamicin Against Gram-Negative Bacteria
Authors: Meyers Burt R. , Leng Bernard , Hirschman Shalom Z.
Published: June 2012

Sisomicin was found to be more active on a weight basis than gentamicin against
Pseudomonas
sp.,
Klebsiella
sp., and indole-positive
Proteus
. Gentamicin was more active than sisomicin against
Escherichia coli, Serratia
sp.,
Enterobacter
sp., and
Proteus mirabilis
. Both antibiotics were very active against methicillin-resistant strains of
Staphylococcus aureus
.
Mechanisms of Ampicillin Resistance in
Haemophilus influenzae
Type B
Authors: Vega R. , Sadoff H. L. , Patterson M. J.
Published: June 2012

The genetic mechanisms associated with ampicillin resistance in strains of
Haemophilus influenzae
type b were investigated. In experiments concerned with transfer of total deoxyribonucleic acid in vitro, expression of resistance by wild-type strains occurred at a frequency of about 10%. The minimum inhibitory concentration of ampicillin for the transformed strains was similar to that of the resistant donor strains, and resistance in transformants was associated with acquisition of the ability to produce beta-lactamase. Exposure to 39 μg of acridine per ml for 18 h cured resistance at a frequency of 80%, and there was spontaneous loss of resistance after repeated subculture of some strains. Analysis by cesium chloride-ethidium bromide density gradient centrifugation demonstrated the presence of extrachromosomal deoxyribonucleic acid in the resistant strains, providing further evidence that the resistance factor is plasmid mediated.
Effect of Virginiamycin on the Growth Cycle of
Bdellovibrio
Authors: Varon M. , Cocito C. , Seijffers J.
Published: June 2012

The two components of virginiamycin, virginiamycin M (VM) and virginiamycin S (VS), were used to explore the life cycle of symbiosis-dependent and -independent strains of
Bdellovibrio bacteriovorus
during multiplication in a two-membered system with either living or heat-inactivated
Escherichia coli
or in axenic cultures. Relatively high concentrations of these inhibitors separately were required to stop growth under all the conditions, but the minimum inhibitory concentration of the single components was reduced 1,000-fold by the association of VM and VS. No dissociation between mass growth and cell division was observed with VM; VS specifically halted cell division without affecting the kinetics of macromolecules formation and overall growth. This effect on cell division was only obtained when the antibiotic was added during the first half of the multiplication cycle and was reversible at any time.
Inhibition of Sporulation by Cerulenin and Its Reversion by Exogenous Fatty Acids in
Saccharomyces cerevisiae
Authors: Ohno Tadao , Awaya Juichi , Ōmura Satoshi
Published: June 2012

Sporulation of
Saccharomyces cerevisiae
G2-2 was inhibited by the antibiotic cerulenin which is known to be a specific inhibitor of fatty acid and sterol synthesis. This inhibition was reversed by various fatty acids, especially by oleic acid (C
18:1
) and pentadecanoic acid (C
15:0
). Ergosterol showed only slight reversibility of this inhibition. When cerulenin was added to the sporulation medium later than 12 h after the start of incubation, the marked inhibition disappeared. When the fatty acid fraction extracted from the sporulated yeasts was added to the cells pretreated with cerulenin for more than 6 h, sporulation became evident 6 h after the fatty acid fraction addition. Therefore, sufficient synthesis of fatty acids required for sporulation was assumed to occur during the first 6 h in phase I of yeast sporulation.
Antibiotic Resistance and Hly Plasmids in Serotypes of
Escherichia coli
Associated with Porcine Enteric Disease
Authors: Jørgensen S. Tue , Poulsen Anna-Lise
Published: June 2012

A total of 359 hemolytic
Escherichia coli
strains, representing eight pig pathogenic serotypes and isolated from pigs with enteric disease, was tested for transferable resistance to eight antibiotics. The co-transfer of plasmids controlling hemolysin production (Hly) with antibiotic resistance plasmids (R-factors) was evaluated. Transferable resistance to tetracycline, streptomycin, and/or sulfonamides was found in 47% of the total number of strains and 80% of the resistant ones. Chloramphenicol resistance was seldom seen. Co-transfer of Hly with R-factors occurred in 22.5% of the strains, generally to a degree excluding a genetic linkage. Stable coexistence of two R-factors in a cell was indicated by transfer patterns in 29 of the strains.
Analysis of Certain Variables in the Agar Dilution Susceptibility Test
Authors: Snyder Robert J. , Kohner Peggy C. , Ilstrup Duane M. , Washington John A.
Published: June 2012

This study examined (i) the activity of gentamicin added to agar in ratios of 1:100 and 1:1,000 to produce a final concentration of 1 μg/ml, (ii) the uniformity of distribution of gentamicin in agar in relation to the amount of mixing, and (iii) the effect of agar depth on the activity of gentamicin against
Pseudomonas aeruginosa
. Although the ratio of antibiotic solution to agar had no significant effects on activity of the antibiotic, the amount of mixing did. Agar depth had no significant effect on the activity of gentamicin.
Elimination of Resistance Determinants from R-Factor R1 by Intercalative Compounds
Authors: Hahn Fred E. , Ciak Jennie
Published: June 2012

Eighteen deoxyribonucleic acid (DNA)-complexing compounds, among them 15 intercalative substances, and, additionally, nalidixic acid eliminated with different frequencies four antibiotic resistance determinants from the R-factor R1, carried by
Salmonella typhimurium
. Eliminating concentrations did not inhibit growth of the bacteria. The most active compound was “nitroacridine II” {1-diethylamino-3-[(6-nitro-9-acridinyl)amino]propanol}. When 14 compounds which had been tested at a standard concentration of 10
−4
M were listed according to decreasing activities of elimination of the four resistance determinants, a nearly consistent activity sequence was revealed. Frequencies of elimination of the kanamycin resistance determinant correlated directly with the binding of compounds to DNA, i.e., with end points of their displacement of methyl green from the methyl green-DNA complex. We propose that the observed eliminations resulted from selective toxicity for plasmidic template DNA and inhibitions of R-factor replication.
Effect of Bleomycin on Deoxyribonucleic Acid Synthesis in Toluene-Treated
Escherichia coli
Cells
Authors: Ross Steven L. , Moses Robb E.
Published: June 2012

The antibiotic bleomycin stimulates deoxyribonucleic acid (DNA) synthesis in toluene-treated
Escherichia coli
cells. The increase in synthesis is linear with bleomycin concentration. Bleomycin-stimulated DNA synthesis is independent of replication and dependent on DNA polymerase I. Replication is spared as the DNA polymerase I-dependent DNA synthesis increases. Bleomycin does not appear to have any effect on purified
E. coli
DNA polymerases I or II. Our results suggest that bleomycin causes nicking of the bacterial chromosome with subsequent DNA synthesis catalyzed by DNA polymerase I.
Synergy in the Antimicrobial Action of Penicillin and β-Chloro-
d
-Alanine In Vitro
Authors: Soper Thomas S. , Manning James M.
Published: June 2012

β-Chloro-
d
-alanine and penicillin G acted on early and late steps, respectively, in the biosynthesis of the bacterial cell wall. In combination these compounds showed a synergistic effect on the growth of
Salmonella typhimurium
and of
Escherichia coli
in vitro.
Unreliability of Direct Antibiotic Susceptibility Testing on Wound Exudates
Authors: Ellner Paul D. , Johnson Erious
Published: June 2012

Direct susceptibility testing was performed on 110 specimens of wound exudates. Growth was inadequate in 76 of these specimens. Of the remaining 34 specimens, only 5 produced results corresponding to those obtained by testing individual bacterial isolates by the Kirby-Bauer technique. This study confirms that direct susceptibility testing of wound exudates may provide misleading and clinically unreliable information on more than 95% of specimens.
Effect of Amphotericin B and Rifampin Against
Coccidioides immitis
In Vitro and In Vivo
Authors: Huppert M. , Pappagianis D. , Sun S. H. , Gleason-Jordan I. , Collins M. S. , Vukovich K. R.
Published: June 2012

Amphotericin B, the principal drug used for treating systemic mycoses, possesses undesirable toxic properties. The ability of this antibiotic to potentiate antifungal activity of other compounds suggests that lower doses of amphotericin B could be used in combination with a second drug without loss of therapeutic efficacy. In vitro tests demonstrated that amphotericin B potentiated rifampin against the mycelial growth phase of
Coccidioides immitis
but not against the spherule-endospore phase. Therapy for murine coccidioidomycosis with a combined amphotericin B-rifampin regimen was not better than treatment with amphotericin B alone; in fact, combined drugs may have been even less effective. This would have clinical significance for therapy of concurrent infections.
Toxicity of Nalidixic Acid on
Candida albicans, Saccharomyces cerevisiae
, and
Kluyveromyces lactis
Authors: Sobieski Rodney J. , Brewer Alan R.
Published: June 2012

The antibacterial drug nalidixic acid (Nal) can suppress the growth of
Candida albicans
at levels of the drug normally found in urine. Growth suppression increases as drug levels are increased, and Nal also causes a similar proportional inhibition of the synthesis of all cellular macromolecules. However, growth temperature (25 versus 37 C) and the divalent cations Mg
2+
and Mn
2+
can increase
C. albicans
resistance to Nal. Also, nitrogen depletion of
Candida
shows that Nal-treated and untreated cells exhibit no difference in leucine uptake during readaptation to nitrogen. In Nal-treated, nitrogen-starved cells, ribonucleic acid and deoxyribonucleic acid (DNA) biosynthesis are less affected than in unstarved Nal-treated cells, but of the two nucleic acids DNA synthesis is the most affected. Nal-resistant strains of
C. albicans
exhibit a slight toxicity for macromolecular synthesis. Nal treatment of a synchronized population of
Saccharomyces cerevisiae
results in an increase in the culture mean doubling time of, at most, 20%, but Nal causes the loss of synchronous cell division. With a synchronized population of
Kluyveromyces lactis
, Nal causes an increase in the mean doubling time of upwards of 300%, with synchrony of cell division being maintained. It is known that
S. cerevisiae
asynchronously synthesizes mitochondrial DNA during the cell cycle, whereas with
K. lactis
it is synchronous. Thus, with
C. albicans
Nal toxicity is dependent both on the dose and the physiological state of the cell. Furthermore, Nal inhibits growth of yeast with synchronous mitochondrial DNA synthesis more adversely than yeast with asynchronous mitochondrial DNA synthesis.
Comparative Study of the In Vitro Antibacterial Activity of Cefoxitin, Cefuroxime, and Cephaloridine
Authors: Norrby Ragnar , Brorsson John-Erik , Seeberg Staffan
Published: June 2012

The in vitro antibacterial effects of cefoxitin, a semisynthetic cephamycin, cefuroxime, a new cephalosporin antibiotic, and cephaloridine were compared. With gram-positive bacteria, marked differences were found only in the effects against
Streptococcus faecalis
, where cephaloridine and cefuroxime were superior to cefoxitin. With gram-negative aerobic bacteria, cefoxitin, which is known to be more resistant to beta-lactamases from gram-negative bacteria than any cephalosporin, was found to be more effective than cefuroxime and cephaloridine against ampicillin-resistant strains of
Escherichia coli
and indole-positive strains of
Proteus. Haemophilus influenzae
was found to be more susceptible to cefuroxime than to cefoxitin and cephaloridine. When ampicillin-resistant strains of
H. influenzae
were tested, markedly higher minimal inhibitory concentration values were obtained with cephaloridine in comparison to those obtained with ampicillin-susceptible strains. These increases in the minimal inhibitory concentration values were not observed with cefoxitin and cefuroxime, probably due to the resistance of these two compounds to beta-lactamases. Strains of
Bacteroides fragilis
were found to be much more susceptible to cefoxitin than to cefuroxime, which in turn was superior to cephaloridine. The results obtained indicate that cefoxitin and cefuroxime both are superior in their antibacterial spectra to the cephalosporins that are now in clinical use.
Nafcillin Treatment of
Staphylococcus aureus
Meningitis
Authors: Ruiz Daniel E. , Warner John F.
Published: June 2012

Serial serum and cerebrospinal fluid nafcillin concentrations were determined in a patient successfully treated with nafcillin (200 mg/kg per day) for
Staphylococcus aureus
bacteremia and meningitis. Nafcillin and methicillin cerebrospinal fluid concentrations were compared.
Pipemidic Acid: Its Activities Against Various Experimental Infections
Authors: Shimizu Masanao , Takase Yoshiyuki , Nakamura Shinichi , Katae Hiromi , Minami Akira , Nakata Katsuhisa , Kurobe Nobuyuki
Published: June 2012

Pipemidic acid, a structural relative of piromidic and nalidixic acids, exhibited substantial therapeutic activity when it was administered orally to mice bearing either widely disseminated or relatively localized infections with
Staphylococcus aureus
and a variety of gram-negative bacilli. The activity of pipemidic acid was always greater than that of piromidic and nalidixic acids; in infections with
Pseudomonas aeruginosa
and in bacilli resistant to the latter two drugs, pipemidic acid exhibited significant activity. In limited comparative studies, the activities of pipemidic acid were generally superior to the activities of cephalexin, ampicillin, and carbenicillin. Gentamicin, administered subcutaneously, was more active than pipemidic acid, given either orally or subcutaneously, against both systemic and localized infections with
P. aeruginosa
. The therapeutic accomplishments of pipemidic acid were attained with well-tolerated doses.
4,4′-Isopropylidine-Bis[2-Isopropyl]Phenol, a New Inhibitor for Cell Wall Formation of
Bacillus subtilis
Authors: Shimi Ibrahim R. , Shoukry Safwat , Zaki Zeinab
Published: June 2012

4,4′-Isopropylidine-bis[2-isopropyl]phenol was found to possess antimicrobial activity against gram-positive bacteria and some fungi, whereas it had no effect on gram-negative organisms. The drug has a potent inhibitory action on the synthesis of cell wall mucopeptides of
Bacillus subtilis
by inhibiting the enzyme
d
-glutamate ligase, which is responsible for the incorporation of
d
-glutamic acid into uridine 5′-diphosphate-muramyl-
l
-alanine. The drug had a weak lytic effect on protoplasts and inhibited protein synthesis, whereas no significant effect on the synthesis of deoxyribonucleic acid and ribonucleic acid was found.
Nystatin-Induced Potassium Efflux from
Saccharomyces cerevisiae
Measured by Flame Photometry: a Potential Bioassay Approach
Authors: Clements-Jewery S.
Published: June 2012

A potential bioassay method for nystatin has been developed based on the ability of this antibiotic to bring out dose-related potassium ion efflux from susceptible cells of
Saccharomyces cerevisiae
, such extracellular potassium ion concentration being measured by flame photometry.
Mutagenic Action of Nitrofurans on
Euglena gracilis
and
Mycobacterium phlei
Authors: Ebringer Libor , Jurášek Adolf , Koníček Jiří , Koníčková Miluše , Lahitova Nora , Trubačík Stanislav
Published: June 2012

There is a pronounced difference between the action of antibiotics and nitrofurans on
Euglena gracilis
. Those antibiotics that induce hereditary loss of chloroplasts do so only when they affect dividing cells. On the other hand, nitrofurans induce a mass mutation in both dividing and nondividing cells (under conditions of continuous illumination of cultures). It was found that a breakdown product, 5-nitro-2-furaldehyde, is liberated from furadantin and furoxone. This intermediate is responsible for the observed specific mutagenicity of 5-nitrofuran drugs. The mutagenic action of 5-nitro-2-furaldehyde is very similar to that of nitrosoguanidine. Both compounds induce bleached mutants of
E. gracilis
when acting on growing or resting cells, regardless of the dark or light conditions. Similarly, both compounds induce reverse mutations in auxotrophic strains of
Mycobacterium phlei
.
Ribonucleic Acid Synthesis Dependent on Exogenous Triphosphates in Nystatin-Treated Cells of
Kluyveromyces lactis
Authors: Badaracco G. , Cassani G.
Published: June 2012

Kluyveromyces lactis
cells treated with nystatin became permeable to ribonucleoside triphosphates. Although not viable, nystatin-treated cells were capable of sustaining ribonucleic acid synthesis. The system depended on the presence of divalent ions and the four nucleoside triphosphates, and was strongly stimulated by ammonium sulfate. The system utilized endogenous deoxyribonucleic acid as template. Synthesis of ribonucleic acid was associated with the cells and probably occurred internally.
Laboratory Evaluation of a Commercial Microbial Control System
Authors: Borchardt Kenneth A.
Published: June 2012

A new product, the 3M Brand Microbial Control System for monitoring the reproducibility of Bauer-Kirby susceptibility tests, was compared with standard ATCC strains of
Escherichia coli, Staphylococcus aureus
, and
Pseudomonas aeruginosa
. Results are presented from four independent laboratories in which all obvious protocol variables, excluding media and personnel, were identical. Evaluation of the system revealed that the commercial procedure was simple to implement and efficacious and produced results equivalent to those derived from ATCC control strains of
E. coli, S. aureus
, and
P. aeruginosa
.
Effect of Semisynthetic Penicillins on the Limulus Lysate Test
Authors: McCullough Karen Z. , Scolnick Sheila A.
Published: June 2012

Semisynthetic penicillins in concentrations greater than 1.0% (wt/vol) were found to inhibit the limulus lysate assay for endotoxin.
Tetracycline-Resistant T-Mycoplasmas (
Ureaplasma urealyticum
) from Patients with a History of Reproductive Failure
Authors: Spaepen Moniek S. , Kundsin Ruth B. , Horne Herbert W.
Published: June 2012

The susceptibilities of T-mycoplasmas (
Ureaplasma urealyticum
) to minocycline, demeclocycline, doxycycline, tetracycline, and erythromycin were determined by a direct tube dilution test. T-mycoplasma-positive urine sediments of 105 patients with a history of reproductive failure were used as inocula. Minocycline was found to be the most active of the group of antibiotics commonly used to eradicate T-mycoplasma infection. Based on the median initial minimum inhibitory concentration, minocycline was the lowest with 0.03 μg/ml, followed by demeclocycline and doxycycline with 0.125 μg/ml, tetracycline with 0.25 μg/ml, and erythromycin with 2.0 μg/ml. Six T-mycoplasma isolates which had been cloned three times were also tested for susceptibility to the same five antibiotics. The same susceptibility pattern was found. Strains resistant to high concentrations of all antibiotics occurred. Strong positive correlation was seen in 21 patients between in vitro highly resistant strains and positive posttreatment cultures. These results indicate that empirical treatment of genital mycoplasma infections is not justified. Cultures should be taken pretreatment, susceptibility testing performed prior to treatment, and follow-up cultures done posttreatment.
Effects of Subinhibitory Concentrations of Antibiotics on Cross Walls of Cocci
Authors: Lorian Victor , Atkinson Barbara
Published: June 2012

Cultures of
Staphylococcus aureus, Neisseria gonorrhoeae
, and
Streptococcus bovis
were incubated on membrane filters on agar containing antibiotics at one-third to one-fourth the minimal inhibitory concentration for the particular bacterial strain.
S. aureus
was grown in the presence of oxacillin, cephaloridine, or lincomycin.
N. gonorrhoeae
and
S. bovis
were grown in the presence of penicillin. The membranes were then incubated in drug-free agar, after which viability was determined and the cells were examined by electron microscopy.
S. aureus
exposed to oxacillin and cephaloridine grew into cells two to seven times larger than normal that contained thick multiple cross walls.
S. aureus
exposed to lincomycin grew into cells 1.5 to 2 times larger than normal, with multiple thick cross walls and periheral cell walls twice the normal thickness.
N. gonorrhoeae
cells exposed to penicillin were slightly larger than normal and had cross walls that were up to eight times thicker than normal. After transfer to drug-free agar, cells became smaller, and some normal organisms could be seen.
S. bovis
incubated in the presence of penicillin grew into filaments that contained no cross walls. Two hours after the return to drug-free agar, filaments with cross walls as well as normal cells were observed. Exposure to subinhibitory concentrations of penicillin did not affect the growth of the peripheral cell wall of
S. aureus, N. gonorrhoeae
, or
S. bovis
, but appeared to inhibit lysis of cross walls in
S. aureus
and
N. gonorrhoeae
and to inhibit the synthesis of cross walls in
S. bovis
; that is, the rates of peripheral and cross wall formation differed in their susceptibility to penicillin. These facts suggest that peripheral growth and cross wall formation in cocci are separable processes.
Effect of Antibiotics on L-Form Induction of
Neisseria meningitidis
Authors: Chin William L. , Lawson John W.
Published: June 2012

Conditions have been developed that permit highly efficient conversion in vitro of all serogroups of
Neisseria meningitidis
to the L-form. During the course of the studies, optimal parameters for cultivation and propogation were determined and compared with those found in studies done by previous workers on meningococci. The plasma expander polyvinylpyrrolidone (PVP) (molecular weight, 40,000) has been incorporated into the medium as an osmotic stabilizer. A method is outlined for removing toxicity (due to impurities in PVP) reported in some earlier studies done in this laboratory. Light and scanning electron microscopy of the L-form inductants and of a stable L-form have shown characteristics distinctive among the strains observed. Finally, the effects of both cell wall and other antibiotics were studied. It was shown that cell wall antibiotics other than the commonly used potassium penicillin G could induce
N. meningitidis
to the L-form, using the PVP-stabilized medium base. Furthermore, the antibiotics vancomycin, colistin, nystatin, and trimethoprim, used at the concentrations found in commercially prepared Transgrow formulations, did not adversely affect meningococcal L-form induction. The system described herein will hopefully serve as an effective tool, specifically in the study of “aseptic” meningitis and possible meningococcal L-form etiology and, more generally, in evaluating the ability of bacterial L-forms to cause disease.
Inhibition of Potentially Pathogenic Yeastlike Fungi by Clotrimazole in Combination with 5-Fluorocytosine or Amphotericin B
Authors: Beggs William H. , Sarosi George A. , Steele Nadine M.
Published: June 2012

Clotrimazole (CTM) has a doubtful future with respect to use in treatment of the systemic mycoses. To assess the potential of CTM in combined drug regimens, antifungal effects of CTM together with 5-fluorocytosine (5-FC) or amphotericin B (AMB) were tested in a synthetic liquid medium against
Candida albicans, Candida tropicalis
, and
Torulopsis glabrata
. Viable counts were monitored over a 48-h incubation period. Weak inhibitory concentrations of CTM were tested in combination with levels of 5-FC or AMB that alone produced transient antifungal effects followed by rapid recovery of proliferative capacity. Results were similar for each of the organisms studied. Between 24 and 48 h, when cultures containing 5-FC or AMB alone were in the recovery phase, CTM plus 5-FC and CTM plus AMB continued to markedly suppress cell multiplication. It would appear that weak inhibitory concentrations of CTM can act together with 5-FC or AMB to produce antifungal effects greater than that obtained with either of the latter two drugs alone.
Activity of Amphotericin B, 5-Fluorocytosine, and Rifampin Against Six Clinical Isolates of
Aspergillus
Authors: Kitahara M. , Seth V. K. , Medoff G. , Kobayashi G. S.
Published: June 2012

Amphotericin B in combination with 5-fluorocytosine was synergistic against three clinical isolates of
Aspergillus fumigatus
and one of three clinical isolates of
A. flavus
. Amphotericin B in combination with rifampin was synergistic against all six clinical isolates of
Aspergillus
tested. The levels of 5-fluorocytosine and rifampin required for synergism were higher than clinically achievable concentrations when measurements of synergism were based on visual turbidity; but when the effects of the drugs were measured by inhibition of ribonucleic acid synthesis or dry-weight increase, much lower concentrations were effective.
WhiB5, a Transcriptional Regulator That Contributes to Mycobacterium tuberculosis Virulence and Reactivation
Authors: Casonato Stefano , Cervantes Sánchez Axel , Haruki Hirohito , Rengifo González Monica , Provvedi Roberta , Dainese Elisa , Jaouen Thomas , Gola Susanne , Bini Estela , Vicente Miguel , Johnsson Kai , Ghisotti Daniela , Palù Giorgio , Hernández-Pando Rogelio , Manganelli Riccardo
Published: June 2012

The proteins belonging to the WhiB superfamily are small global transcriptional regulators typical of actinomycetes. In this paper, we characterize the role of WhiB5, a
Mycobacterium tuberculosis
protein belonging to this superfamily. A null mutant was constructed in
M. tuberculosis
H37Rv and was shown to be attenuated during both progressive and chronic mouse infections. Mice infected with the mutant had smaller bacillary burdens in the lungs but a larger inflammatory response, suggesting a role of WhiB5 in immunomodulation. Most interestingly, the
whiB5
mutant was not able to resume growth after reactivation from chronic infection, suggesting that WhiB5 controls the expression of genes involved in this process. The mutant was also more sensitive than the wild-type parental strain to
S
-nitrosoglutathione (GSNO) and was less metabolically active following prolonged starvation, underscoring the importance of GSNO and starvation in development and maintenance of chronic infection. DNA microarray analysis identified 58 genes whose expression is influenced by WhiB5, including
sigM
, encoding an alternative sigma factor, and genes encoding the constituents of two type VII secretion systems, namely, ESX-2 and ESX-4.
Draft Genome Sequence of the Volcano-Inhabiting Thermoacidophilic Methanotroph Methylacidiphilum fumariolicum Strain SolV
Authors: Khadem Ahmad F. , Wieczorek Adam S. , Pol Arjan , Vuilleumier Stéphane , Harhangi Harry R. , Dunfield Peter F. , Kalyuzhnaya Marina G. , Murrell J. Colin , Francoijs Kees-Jan , Stunnenberg Henk G. , Stein Lisa Y. , DiSpirito Alan A. , Semrau Jeremy D. , Lajus Aurélie , Médigue Claudine , Klotz Martin G. , Jetten Mike S. M. , Op den Camp Huub J. M.
Published: June 2012

The draft genome of
Methylacidiphilum fumariolicum
SolV, a thermoacidophilic methanotroph of the phylum
Verrucomicrobia
, is presented. Annotation revealed pathways for one-carbon, nitrogen, and hydrogen catabolism and respiration together with central metabolic pathways. The genome encodes three orthologues of particulate methane monooxygenases. Sequencing of this genome will help in the understanding of methane cycling in volcanic environments.