scholarly journals Lon Protease Is Essential for Paradoxical Survival of Escherichia coli Exposed to High Concentrations of Quinolone

2009 ◽  
Vol 53 (7) ◽  
pp. 3103-3105 ◽  
Author(s):  
Muhammad Malik ◽  
Joseph Capecci ◽  
Karl Drlica
Keyword(s):  
Escherichia Coli ◽  
Dna Lesions ◽  
Lon Protease ◽  
High Drug ◽  
Cell Lysate ◽  
Drug Concentrations ◽  
Parallel Increase ◽  
High Concentrations ◽  
Dna Size ◽  
Very High

ABSTRACT A deficiency of the Escherichia coli Lon protease blocked paradoxical survival occurring at very high nalidixic acid concentrations. The absence of Lon also blocked a parallel increase in cell lysate viscosity likely to reflect DNA size. Thus, Lon may participate in repairing quinolone-mediated DNA lesions formed at high drug concentrations.

scholarly journals Paradoxical Effect of Caspofungin: Reduced Activity against Candida albicans at High Drug Concentrations

2004 ◽  
Vol 48 (9) ◽  
pp. 3407-3411 ◽  
Author(s):  
David A. Stevens ◽  
Marife Espiritu ◽  
Rachana Parmar
Keyword(s):  
Candida Albicans ◽  
Resistance Mechanisms ◽  
Paradoxical Effect ◽  
Fungal Cell ◽  
High Drug ◽  
Minimum Fungicidal Concentration ◽  
Drug Concentrations ◽  
High Concentrations ◽  
Glucan Synthesis

ABSTRACT Resistance problems with caspofungin, an echinocandin inhibitor of fungal cell wall glucan synthesis, have been rare. We noted paradoxical turbid growth of Candida albicans isolates in broth in some high (supra-MIC) concentrations. Among isolates submitted for susceptibility testing and screened at drug concentrations up to 12.5 μg/ml, the frequency was 16%. Analysis of the turbid growth indicated slowing of growth in the presence of drug but with numbers of CFU up to 72% those of drug-free controls. Clearing of growth again by the highest drug concentrations produced a quadriphasic pattern in a tube dilution series. Cells growing at high drug concentrations were not resistant on retesting but showed the paradoxical effect of the parent. Among a selected series of isolates tested at concentrations up to 50 μg/ml, an additional 53% showed a “mini-paradoxical effect”: no turbid growth but incomplete killing at high concentrations (supra-minimum fungicidal concentration). These effects were reproducible; medium dependent in extent; noted in macro- and microdilution, in the presence or absence of serum, and on agar containing drug (but not when drug concentrations were not constant, as in agar diffusion); not seen with other echinocandins and less commonly in other Candida species; and not due to destruction of drug in tubes showing the effect. Cooperative enhancement of inhibition by a second drug could eradicate the effect. We postulate that high drug concentrations derepress or activate resistance mechanisms. The abilities of subpopulations to survive at high drug concentrations could have in vivo consequences.

scholarly journals Fluoroquinolone action in mycobacteria: similarity with effects in Escherichia coli and detection by cell lysate viscosity.

1996 ◽  
Vol 40 (7) ◽  
pp. 1594-1599 ◽  
Author(s):  
K Drlica ◽  
C Xu ◽  
J Y Wang ◽  
R M Burger ◽  
M Malik
Keyword(s):  
Escherichia Coli ◽  
Dna Cleavage ◽  
Bactericidal Effect ◽  
Multidrug Resistant ◽  
E Coli ◽  
Cell Lysate ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
High Concentrations ◽  
Inhibitor Of Protein Synthesis

Fluoroquinolones are potent antibacterial agents that are being used as therapeutic agents for the treatment of multidrug-resistant tuberculosis. To better understand fluoroquinolone action in mycobacteria, the effects of ciprofloxacin were examined. DNA synthesis was inhibited rapidly in Mycobacterium smegmatis, DNA cleavage was readily observed by an empirical assay of cell lysate viscosity, and cell growth was blocked. These data are explained by the formation of gyrase-DNA-ciprofloxacin complexes that block replication fork movement. The bactericidal action of ciprofloxacin against M. smegmatis, Mycobacterium bovis BCG, and Escherichia coli occurred more slowly in cells with longer doubling times. The bactericidal effect against M. bovis BCG was partially blocked by pretreatment with chloramphenicol, an inhibitor of protein synthesis, and by very high concentrations of ciprofloxacin itself. Similar responses occur when E. coli is treated with ciprofloxacin. These similarities between E. coli and mycobacteria indicate that results from extensive fluoroquinolone studies with E. coli can be applied to mycobacteria. A simple viscometric assay of DNA cleavage is described. The assay is expected to be useful for screening new fluoroquinolone derivatives for increased effectiveness against clinically important bacteria.

scholarly journals Identification of Escherichia coli Genes Essential for High-Level, Clinically Relevant, Resistance to Antibiotics

2021 ◽  
Author(s):  
Esmeralda Z Reyes Fernandez ◽  
Noemie Alon Cudkowicz ◽  
Sonia Steiner Mordoch ◽  
Shimon Schuldiner
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Molecular Mechanisms ◽  
E Coli ◽  
Novel Approach ◽  
Public Health Challenges ◽  
High Concentrations ◽  
New Perspective ◽  
High Level ◽  
Very High

Antibiotic resistance is one of the biggest public health challenges of our time. Here we present a novel approach to recognizing molecular mechanisms essential for maintaining high-level clinically relevant antibiotic resistance. To identify essential genes in this context, we subjected Escherichia coli EV18, a strain highly resistant to quinolones, to random transposon mutagenesis. This strain's unique advantage is that the screen is performed at very high concentrations of the antibiotic, non-permissive for most strains. The transposon's insertion affected the transcription of five genes required for the maintenance of resistance in EV18. Three of these genes (YihO, YhdP, and WaaY) have not been previously identified as essential for high-level antimicrobial resistance (AMR). Our work provides a new perspective to identify and characterize novel players crucial for maintaining AMR in E. coli.

The metachor as a characteristic of the association of electrolytes in aqueous solutions

1984 ◽  
Vol 49 (5) ◽  
pp. 1061-1078 ◽  
Author(s):  
Jiří Čeleda ◽  
Stanislav Škramovský
Keyword(s):  
Aqueous Solutions ◽  
Apparent Volume ◽  
Solutions Of Electrolytes ◽  
Molal Volumes ◽  
The Difference ◽  
High Concentrations ◽  
Experimental Values ◽  
Suitable Characteristic ◽  
Association Of Ions ◽  
Very High

Based on the earlier paper introducing a concept of the apparent parachor of a solute in the solution, we have eliminated in the present work algebraically the effect which is introduced into this quantity by the additivity of the apparent molal volumes. The difference remaining from the apparent parachor after substracting the contribution corresponding to the apparent volume ( for which the present authors suggest the name metachor) was evaluated from the experimental values of the surface tension of aqueous solutions for a set of 1,1-, 1,2- and 2,1-valent electrolytes. This difference showed to be independent of concentration up to the very high values of the order of units mol dm-3 but it was directly proportional to the number of the free charges (with a proportionality factor 5 ± 1 cm3 mol-1 identical for all studied electrolytes). The metachor can be, for this reason, a suitable characteristic for detection of the association of ions and formation of complexes in the solutions of electrolytes, up to high concentrations where other methods are failing.

scholarly journals Nitrification Process in a Nuclear Wastewater with High Load of Nitrogen, Uranium and Organic Matter under ORP Controlled

Water ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1607
Author(s):  
Mariano Venturini ◽  
Ariana Rossen ◽  
Patricia Silva Paulo
Keyword(s):  
Ammonia Oxidation ◽  
High Load ◽  
Nuclear Fuels ◽  
Monod Model ◽  
Nernst Equation ◽  
Nitrification Process ◽  
Real Wastewater ◽  
High Concentrations ◽  
Wastewater Samples ◽  
Very High

To produce nuclear fuels, it is necessary to convert uranium′s ore into UO2-ceramic grade, using several quantities of kerosene, methanol, nitric acid, ammonia, and, in low level, tributyl phosphate (TBP). Thus, the effluent generated by nuclear industries is one of the most toxic since it contains high concentrations of dangerous compounds. This paper explores biological parameters on real nuclear wastewater by the Monod model in an ORP controlled predicting the specific ammonia oxidation. Thermodynamic parameters were established using the Nernst equation to monitor Oxiders/Reductors relationship to obtain a correlation of these parameters to controlling and monitoring; that would allow technical operators to have better control of the nitrification process. The real nuclear effluent is formed by a mixture of two different lines of discharges, one composed of a high load of nitrogen, around 11,000 mg/L (N-NH4+-N-NO3−) and 600 mg/L Uranium, a second one, proceeds from uranium purification, containing TBP and COD that have to be removed. Bioprocesses were operated on real wastewater samples over 120 days under controlled ORP, as described by Nernst equations, which proved to be a robust tool to operate nitrification for larger periods with a very high load of nitrogen, uranium, and COD.

scholarly journals Halogenated Volatile Organic Compounds in Water Samples and Inorganic Elements Levels in Ores for Characterizing a High Anthropogenic Polluted Area in the Northern Latium Region (Italy)

2021 ◽  
Vol 18 (4) ◽  
pp. 1628
Author(s):  
Mario Vincenzo Russo ◽  
Ivan Notardonato ◽  
Alberto Rosada ◽  
Giuseppe Ianiri ◽  
Pasquale Avino
Keyword(s):  
Organic Compounds ◽  
Mean Value ◽  
Greenhouse Crops ◽  
River Waters ◽  
Liquid Liquid Extraction ◽  
Volatile Organic ◽  
High Concentrations ◽  
Very High ◽  
Inorganic Fraction

This paper shows a characterization of the organic and inorganic fraction of river waters (Tiber and Marta) and ores/soil samples collected in the Northern Latium region of Italy for evaluating the anthropogenic/natural source contribution to the environmental pollution of this area. For organic compounds, organochloride volatile compounds in Tiber and Marta rivers were analyzed by two different clean-up methods (i.e., liquid–liquid extraction and static headspace) followed by gas chromatography–electron capture detector (GC-ECD) analysis. The results show very high concentrations of bromoform (up to 1.82 and 3.2 µg L−1 in Tiber and Marta rivers, respectively), due to the presence of greenhouse crops, and of chloroform and tetrachloroethene, due to the presence of handicrafts installations. For the qualitative and quantitative assessment of the inorganic fraction, it is highlighted the use of a nuclear analytical method, instrumental neutron activation analysis, which allows having more information as possible from the sample without performing any chemical-physical pretreatment. The results have evidenced high levels of mercury (mean value 88.6 µg g−1), antimony (77.7 µg g−1), strontium (12,039 µg g−1) and zinc (103 µg g−1), whereas rare earth elements show levels similar to the literature data. Particular consideration is drawn for arsenic (414 µg g−1): the levels found in this paper (ranging between 1 and 5100 µg g−1) explain the high content of such element (as arsenates) in the aquifer, a big issue in this area.

THE SELECTIVE PROTEOLYTIC ENZYME INHIBITORY ACTION OF BENZETHONIUM CHLORIDE

1960 ◽  
Vol 38 (1) ◽  
pp. 25-32 ◽  
Author(s):  
Ivan T. Beck ◽  
E. Pinter ◽  
R. D. McKenna ◽  
H. Griff
Keyword(s):  
Subcutaneous Injection ◽  
Proteolytic Enzyme ◽  
Inhibitory Action ◽  
Hemorrhagic Pancreatitis ◽  
Benzethonium Chloride ◽  
Tryptic Activity ◽  
High Concentrations ◽  
Acute Hemorrhagic Pancreatitis ◽  
Very High

Acute hemorrhagic pancreatitis in humans is thought to be perpetuated by the autolytic processes catalyzed by trypsin and lipase. This study is an integral part of our search for trypsin and lipase inhibitors to be used in the treatment of this disease.Benzethonium chloride was found to inhibit tryptic activity in vitro. The proteolytic activity of rabbit's serum was inhibited, and the inhibition was most pronounced 6 to 12 hours after the subcutaneous injection of the compound. Fibrinolysin was also inhibited in vitro but benzethonium chloride had no inhibitory action on chymotrypsin, pepsin, or lipase.Serum proteins in vitro were precipitated only with very high concentrations of the compound. No significant protein changes were observed in sera of rabbits after the subcutaneous injection of the compound.

scholarly journals High Concentrations of Excised Oxidative DNA Lesions in Human Cerebrospinal Fluid

2003 ◽  
Vol 49 (7) ◽  
pp. 1218-1221 ◽  
Author(s):  
Rafał Rozalski ◽  
Piotr Winkler ◽  
Daniel Gackowski ◽  
Tomasz Paciorek ◽  
Heliodor Kasprzak ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Dna Lesions ◽  
Human Cerebrospinal Fluid ◽  
High Concentrations

scholarly journals Arginine Inhibits Serpins

2007 ◽  
Vol 13 (2) ◽  
pp. 213-218
Author(s):  
Thomas W. Stief
Keyword(s):  
Esterase Activity ◽  
Serine Proteases ◽  
Biological Fluid ◽  
Microtiter Plate ◽  
Human Albumin ◽  
Amidolytic Activity ◽  
Peptide Substrates ◽  
Plate Reader ◽  
High Concentrations ◽  
Very High

Serine protease inactivators (serpins) are important regulators in biochemistry. Often it is necessary to block the serpin action, that is, to stabilize the sample. The guanidine group of arginine is the ligand for the active center pocket of many serine proteases. Arginine or guanidine inhibits serine proteases, and arginine belongs to the reactive P1-P1' center of many serpins. The plasmatic antithrombin, antiplasmin, or anti-C1-esterase activity was determined: A total of 20 µL of pooled normal plasma or 7% human albumin was added to 100 µL of 0—2.67 M arginine, pH 8.6, 10 µL of 26 mIU/mL thrombin in 7% human albumin, and 30 µL of 1.7 mM CHG-Ala-Arg-pNA (37°C). ΔA at 405 nm was determined, by using a microtiter plate reader. Thrombin was substituted by plasmin or C1-esterase, and the chromogenic peptide substrates <Glu-Phe-Lys-pNA or MeOC-Lys(eCBO)-Gly-Arg-pNA, respectively, were used. The IC50 of arginine against plasmatic antithrombin activity is 580 mM; the IC 25 is 440 mM. The IC25 of arginine against plasmatic α 2-antiplasmin or C1-inactivator is 1650 mM. The amidolytic activity of thrombin, plasmin, and C1-esterase is inhibited similarly by arginine: the IC50 for arginine against the amidolytic activity of these proteases is about 400 mM. Arginine at very high concentrations inhibits serpins. This is important, if stabilization of a biological fluid is a prerequisite for valid activities of serine proteases. In addition, these high concentrations of arginine might be a new gentle principle to inhibit pathogens that need serpins for their pathophysiology.

Sign in / Sign up

Export Citation Format

Share Document